Epidemiology

Chlamydia is caused by Chlamydia trachomatis, an obligate intracellular gram‐negative bacterium. Chlamydia is the most reported STI worldwide. Based on prevalence data from 2009 to 2016, the estimated pooled global prevalence of chlamydia in 15–49‐year‐old women is 3.8% (95% uncertainty interval [UI]: 3.3–4.5) and in men 2.7% (95% UI: 1.9–3.7).⁹ In 2016, 403,807 cases of chlamydia were reported in 26 European Union (EU)/European Economic Area (EEA) member states, with an overall notification rate of 185 cases per 100,000 population.

Clinical Presentation

Patients acquire chlamydia via vaginal, anal, or oral sex with an infected partner. Chlamydia commonly causes genital infections in the cervix, urethra, or epididymis. Cervicitis is often asymptomatic in women. Urethritis manifests as pain or difficulty urinating, with or without cervical or penile discharge. Men who engage in receptive anal intercourse can also develop prostate infections.^10,11 Extragenital infections commonly present as pharyngitis and conjunctivitis.

In women, chlamydia infections can ascend to the fallopian tubes, ovaries, or uterus, causing pelvic inflammatory disease (PID). Left untreated, PID can lead to scarring, infertility, and ectopic pregnancies. Infections can also rarely ascend into the abdomen and cause liver abnormalities as well. Complications among males include infections of the epididymis and testes. Both male and female patients can also rarely develop a reactive arthritis.

Some Chlamydia trachomatis strains have an atypical presentation. Specifically, serovars (serologic variants) L1, L2, and L3 cause lymphogranuloma venereum (LGV), which manifests as genital ulcers with lymphadenopathy and requires different antibiotic management. LGV is managed differently than standard Chlamydia trachomatis infections and is more common in Africa, India, Southeast Asia, and the Caribbean. However, outbreaks have been reported outside of these areas. Due to breakdown of the mucosal barriers, patients with chlamydia are at greater risk of acquiring other STIs, including HIV.^10,11

Diagnosis

Chlamydia trachomatis is generally diagnosed via nucleic acid amplification testing (NAAT) on cervical, ureteral, oral, rectal, or urinary specimens.¹⁰

Treatment

Doxycycline and azithromycin are the preferred antibiotics to treat Chlamydia trachomatis infections. Antibiotic recommendations between these two agents are often dictated by national and regional susceptibility data. For example, the British Association for Sexual Health and HIV (BASHH) recommends doxycycline.¹⁰ However, either agent is considered acceptable in the United States.¹²

Oral/Facial Considerations

Patients can also acquire chlamydia infections in the oropharynx via oral sex. Oral infections are often asymptomatic, but fever and lymphadenopathy may occur. Tonsillar infections typically manifest as erythema with small punctate lesions. Lesions may also occur uncommonly in other locations in the mouth and are described as being erythematous, pustular, erosive, or ulcerated.¹³

Epidemiology

Gonorrhea is caused by Neisseria gonorrhoeae, a gram‐negative bacterium. The 2016 global incidence of gonorrhea was 0.9% (95% UI: 0.7–1.1) in women and 0.7% (95% UI: 0.5–1.1) in men. Among men and women aged 15–49 years, there were 87 million new cases of gonorrhea in 2016 globally.⁸ In Europe, gonorrhea is more common in men, and 48% of all reported cases were in men who have sex with men (MSM). Gonorrhea is more common in younger individuals.¹⁴ In the United States, recent trends demonstrate an increase in the incidence of gonorrhea.¹⁵

Clinical Presentation

Gonorrhea infects the same anatomic sites as chlamydia, and symptoms between the two infections overlap. For example, patients can also develop cervicitis, urethritis, epididymitis, conjunctivitis, and pharyngitis. Similarly, women can develop PID, ectopic pregnancy, and infertility as a complication. Gonorrhea can also be asymptomatic, like chlamydia. However, gonorrhea can manifest a disseminated infection, which classically involves the joints.

Diagnosis and Treatment

Like chlamydia, gonorrhea is diagnosed via NAAT. This can be performed in the urine and on swabs from the urethra, cervix, vagina, or oropharynx. Patients with suspected gonorrhea should be referred to a genitourinary medicine clinic for specimen collection, culture, partner notification, and treatment.¹⁶ First‐line therapy to treat gonorrhea is ceftriaxone. However, recent increases in antimicrobial resistance to ceftriaxone have been observed.¹⁷ Like chlamydia, gonorrhea damages mucous membranes, which increases the risk of HIV and other STIs.^18,19

Oral/Facial Considerations

Oropharyngeal gonorrhea is often asymptomatic.²⁰ When symptomatic, it can present with nonspecific multiple ulcers, fiery red oral mucosa, pseudomembrane, painful pharyngitis, atypical gingivitis, and lymphadenopathy (see Figures 21‐1 and 21‐2).

Epidemiology

Syphilis is caused by Treponema pallidum, a spirochete bacterium. It is acquired primarily through sexual contact. The estimated pooled global prevalence of syphilis is 0.5% (95% UI: 0.4–0.6) for both men and women, with regional values ranging from 0.1% to 1.6 %.⁸ Like chlamydia and gonorrhea, syphilis is more common in younger individuals and MSM. Recent trends suggest that the incidence of syphilis has been increasing.^21,22

Clinical Presentation

Syphilis is often considered the “great imitator” because patients can present in a variety of ways. In general, active syphilis infections can be divided into primary, secondary, and tertiary stages. Primary infections occur generally within the first month of exposure. Patients will classically present with a painless genital ulcer (chancre) at the initial inoculation site (Figure 21‐3A, B). However, some patients may not develop or recall developing an ulcer. In secondary syphilis, patients develop a disseminated infection, which manifests as a diffuse rash (classically on the palms and soles).^22–24 In tertiary syphilis, which is very rare, patients classically present with a cardiovascular infection or a syphilitic gumma. Cardiovascular manifestations classically are aneurysms. However, patients may also present with aortic regurgitation and coronary ostial occlusive disease.²⁵

Syphilis may be passed from an infected mother to her child during pregnancy, causing congenital syphilis. Patients with congenital syphilis may have deformed bones, severe anemia, jaundice, hepatomegaly, splenomegaly, blindness, deafness, meningitis, or skin rash.^22–24

Diagnosis

Syphilis is diagnosed using a combination of treponemal and nontreponemal tests (Figure 21‐3C, D). Consultation with a physician is strongly considered when interpreting syphilis diagnostic test results. Treponemal antibody tests will remain positive after patients receive treatment. Quantitative nontreponemal tests should decline after treatment, but the results may never return to negative.²⁴

Treatment

Syphilis is treated based on the duration and severity of disease. Consultation with a physician is strongly recommended prior to initiating syphilis treatment. In general, early syphilis (<1 year) is usually treated with a single dose of intramuscular (IM) benzathine penicillin G. Late syphilis (>1 year) is treated with IM penicillin once weekly for three consecutive weeks. Patients who have evidence of neurologic involvement (neurosyphilis) require intravenous (IV) penicillin for 10–14 days.²⁶

Oral/Facial Considerations

Approximately 15% of patients with primary syphilis will present with highly infectious intraoral chancres, as either solitary or multiple lesions. Chancres typically present as painless, sometimes necrotic, ulcers with a rolled border and associated lymphadenopathy. Common sites of occurrence are the lips, tongue, palate, and nostrils. Lymphadenopathy commonly accompanies these lesions. As mentioned previously, the lesions heal spontaneously without treatment.¹³ If there is a clinical concern for syphilis, patients should still seek medical care, even if the lesion has healed.

Typical oral lesions in secondary syphilis are described as a mucous patch, which presents as thickened whitish plaque affecting the oral mucosa. Necrosis and sloughing may occur. Commonly affected sites include the tongue, lip, buccal mucosa, and palate. These patients may also present with mucosal ulcers and erythematous macular lesions.²⁷ Syphilis‐related gummas classically occur on the hard palate, but may also occur on the soft palate and the alveolus. A gumma begins as a swelling, which eventually ulcerates and then goes through repeated phases of healing and breakdown. Bone destruction of the hard palate may occur with palatal perforation and, in some cases, oral nasal fistula. A gumma may erode into underlying blood vessels.²⁸

Infants with congenital syphilis may also develop orofacial malformations, including Hutchinson’s notched incisors, mulberry‐shaped molar teeth, corneal keratitis, frontal bossing, saddle nose, and hard palate defects.²³

Epidemiology

Actinomyces spp. naturally colonize the oropharynx (Figure 21‐4), gastrointestinal tract, and pelvis in humans. Infections with Actinomyces spp. (called actinomycosis) rarely occur. The annual incidence is fewer than 1/300,000 per year. The incidence of actinomycosis has thought to have declined due to an overall improvement in oral hygiene over time. The male:female ratio is between 1.5:1 and 3:1.^29–32 Risk factors for acquiring actinomycosis include poor oral hygiene; local tissue damage by trauma, recent surgery, or irradiation; intrauterine devices (IUDs) for pelvic infections; and diabetes.^32,33

Clinical Presentation

Actinomycosis commonly occurs in the orocervical (50%), thoracic (20%), and abdominal pelvic regions (20%). Over time, the infection will slowly erode through facial planes and develop chronic sinus tracts. Most infections are thought to occur due to muscular injury, allowing the bacteria to penetrate into body areas and grow in an anaerobic environment.^31,32

Diagnosis

The differential diagnosis for actinomycosis includes cancer, TB, appendicitis, pneumonia, and PID. Most cases are diagnosed when a biopsy reveals classic gram‐positive filamentous bacteria with or without “sulfur granules.” However, the term sulfur granules is a misnomer. These granules are actually composed of a protein–polysaccharide complex and are mineralized by host calcium. Although difficult to achieve, actinomycosis can sometimes be cultured under anaerobic conditions. Other diagnostic approaches, such as immunohistologic, polymerase chain reaction (PCR), and serologic techniques, are generally not commercially available.^31,32

Treatment

Actinomycosis is treated with a prolonged course of systemic antibiotics with or without surgery. Penicillin‐based antibiotics (penicillin, amoxicillin, amoxicillin‐clavulanate) are preferred.^31,32

Consultation with an infectious diseases doctor is recommended to assist with antibiotic monitoring and treatment duration.

Oral/Facial Considerations

Orocervicofacial actinomycosis classically develops after dental manipulation, oral trauma, or in the setting of poor oral hygiene. Patients generally present soft tissue swelling, in or near the mandible. However, infections also occur in the check, chin, and maxilla. Like other forms of actinomycosis, patients will slowly develop sinus tracts with or without sulfur granules. Complications include myositis and osteomyelitis. The differential diagnosis includes malignancies and granulomatous diseases.^30,31,34

Epidemiology and Clinical Presentation

TB is caused by Mycobacterium tuberculosis. Individuals acquire TB by inhaling airborne particles from other infected people. Once inhaled, TB proliferates inside of alveolar macrophages. When enough macrophages are recruited, local complexes of enlarged lymph nodes can be seen on a chest radiograph. These are called “ghon complexes,” where TB can remain dormant for decades. Patients who initially develop TB (also called the primary disease stage) generally have fevers and other nonspecific symptoms. Once primary TB symptoms resolve, patients are considered to have latent TB. This means that they likely still have residual TB bacteria, which can reactivate at some point later in life.

Only about 10% of patients will develop reactivation TB later in life. When reactivated, TB generally presents with a chronic respiratory infection with cough, fevers, night sweats, and weight loss. Patients classically have an upper lobe cavitary lesion on chest radiographs. However, TB can reactivate anywhere in the body.^35,36

TB is a major global health problem. Worldwide there were 10.0 million (range: 9.0–11.1 million) individuals diagnosed with TB in 2018.³⁷ Although the incidence of TB remains stable in most nations, multidrug‐ and extensively drug‐resistant TB remains a growing public health concern.³⁸

Medical risk factors for TB include HIV, diabetes, malnutrition, smoking, and alcohol use (Table 21‐1).^39–41 Societal risk factors for TB include overcrowding, poorly ventilated housing, malnutrition, smoking, stress, social deprivation, and poor social capital.⁴² In industrialized countries, most cases occur in minority groups, particularly recent immigrants from countries with high TB endemicity.

Latent TB can be diagnosed two different ways. The most common approach is tuberculin skin testing on the forearm with purified protein derivative (PPD), a mycobacterial antigen. Interferon gamma release assays (IGRA), are blood tests that detects sensitization to Mycobacterium tuberculosis.^35,38,43 In the United States, the Centers for Disease Control (CDC) recommend screening certain high‐risk populations for latent TB (Table 21‐2). Patients with a positive screening test should be evaluated for the presence of active TB disease. However, a negative latent TB screening test should not be used to rule out active TB.

Diagnosis

Active TB is generally diagnosed via culture of the bacterium. To improve the test sensitivity, serial sampling of respiratory tract specimens is common. Special acid‐fact bacteria (AFB) stains can aid in diagnosis, but these are nonspecific. Newer PCR‐based platforms are often used in conjunction with standard AFB stains and culture.^35,38,43

Treatment

Patients with latent TB receive different treatment regimens than those with active disease. Those with latent TB require a prolonged course of one or two antibiotics. They are often screened for underlying medical problems prior to initiating therapy.⁴⁴ Patients with active TB generally receive a combination of four different antibiotics when they start treatment (Table 21‐3). Adherence to antibiotics is frequently monitored via directly observed therapy. After a couple of weeks of therapy, treatment regimens are generally modified based on adherence, tolerability, and clinical response. The usual course of therapy is six to nine months and involves several drug regimens (Table 21‐3).⁴⁴ However, antibiotic selection and treatment regimens may vary if patients have known or suspected drug‐resistant TB. Drug‐resistant TB is more challenging to treat and may require IV antibiotics.^38,45 Patients with multidrug‐ or extensively drug‐resistant TB require often require complex antibiotic treatment regimens for a prolonged period of time. Despite these intensive regimens, patients with extensively drug‐resistant TB frequently have poor outcomes.^44,46

Public health efforts to combat TB include educational interventions, vaccination, screening high‐risk patients, contact tracing, and early diagnosis and treatment.⁴⁴ Bacillus Calmette‐Guerin (BCG) is a live vaccine made from a weakened strain of Mycobacterium bovis. BCG continues to be administered in many developing countries, but it is not routinely used in the United States and is rarely administered in the United Kingdom. Contact tracing to identify and screen close contacts of recently diagnosed TB patients is considered an important part of combating TB. In hospital settings, patients are placed in airborne isolation, with precautions such as N95 respirators to reduce TB transmission to healthcare workers.^44,47,48

Oral/Facial Considerations

Oral manifestations may occur in up to 3% of patients with long‐term active TB. Lesions may occur in the oral tissues and the neck lymph nodes. The latter is termed scrofula. Oral lesions can be found in various soft tissues and very occasionally in supporting bone. Oral lesions may be primary or secondary to pulmonary tuberculosis. Stellate ulcers affecting the dorsal surface of the tongue are a classic presentation. A TB oral ulcer usually has undermined edges and a granulating floor, but the clinical picture can be variable. Lesions may also affect the gingiva, floor of the mouth, palate, lips, and buccal mucosa (Figure 21‐5). Macroglossia, parotitis, intraosseous lesions, periauricular swelling, and trismus have been reported in some oral TB cases.⁴⁹

Standard fluid‐resistant masks likely provide some protection against TB for dental healthcare personnel. However, routine dental care should be deferred in patients who remain contagious with TB. In the United States, patients with TB are no longer considered contagious if they meet the following criteria: (1) three consecutive AFB sputum smears collected at 8–24‐hour intervals; (2) compliant with an adequate treatment regimen for at least two weeks; and (3) improvement in symptoms. If oral care must be provided for a patient who is contagious with TB, patients should be placed in a negative‐pressure room and healthcare workers should wear an N95‐, FFP2‐, or FFP3‐level respirator. If an oral medicine provider plans on treating a patient with active TB, it is strongly recommended to consult with an infection prevention specialist or hospital epidemiologist, who may be able to share clinic‐ or hospital‐specific protocols. TB protocols may recommend scheduling the patient as the last case of the day to minimize exposure to other patients and staff. TB patients should be instructed to wear a surgical mask while in patient care areas. High‐efficiency particulate air (HEPA) filters may also be used to filter out TB. Consultation with the multidisciplinary TB team is strongly recommended in these cases.^44,47,50

Epidemiology

Blastomyces dermatitidis is a dimorphic fungus that can grow either as a yeast or in mycelial form. Most cases occur in the United States and Canada. It is a normal inhabitant of soil and agricultural and construction workers are at highest risk of infection, particularly those working in the Mississippi and Ohio River Valleys, around the Great Lakes, and near the St. Lawrence Seaway. This geographic distribution has led to the designation by some as “North American blastomycosis.” However, cases of blastomycosis infections have also been described in Mexico and Central and South America.⁵³

In the United States, the yearly incidence is about 1–2 cases per 100,000 population; Wisconsin has the highest rates in the US with between 10 and 40 cases per 100,000 population. Some 1,216 blastomycosis‐related deaths occurred during 1990–2010 in the United States, with an overall age‐adjusted mortality rate of 0.21 per 1 million person‐years.⁵⁴

Clinical Presentation

Both immunocompetent and immunocompromised individuals can develop blastomycosis. Risk factors for blastomycosis include outdoor activities such as forestry work, hunting, and camping. Immunosuppressed patients, such as HIV patients, solid organ transplant patients, and those receiving tumor necrosis factor (TNF) antagonists, are also at higher risk for developing blastomycosis.^54,55

Patients with blastomycosis generally present with pneumonia due to inhaling fungal spores. Immunocompetent patients frequently present with indolent symptoms such as malaise, low‐grade fever, and mild cough. If the infection goes untreated, the signs and symptoms may progress to include dyspnea, weight loss, and production of blood‐tinged sputum.⁵⁶ Some patients develop acute respiratory distress syndrome, with a mortality rate of up to 50–89%.⁵⁵ Disseminated blastomycosis occurs more frequently in immunosuppressed individuals such as those with HIV or organ transplant recipients.⁵⁶

Most blastomycosis infections are localized to the lung, but 25–40% will develop extrapulmonary infection leading to cutaneous, osteoarticular, genitourinary, or central nervous system (CNS) disease. This is usually due to the spread of organisms from the pulmonary lesions through the lymphatic system. The skin lesions (typically on exposed surfaces) start as subcutaneous nodules, slowly progressing to well‐circumscribed indurated ulcers.⁵⁷

Diagnosis

The differential diagnosis for blastomycosis is broad and includes other fungal pathogens and atypical bacteria, including tuberculosis. Blastomycosis can be diagnosed using real‐time nucleic acid detection, antibody identification through enzyme immunoassay, antigen detection, biopsy, and culture on Sabouraud agar.^58–60 Blastomycosis characteristically has broad‐based unipolar budding yeast forms on histology.⁵⁸ Clinically, it is diagnosed via a positive blastomycosis antibody in the setting of a compatible clinical presentation, including appropriate epidemiologic risk factors.

Treatment

All cases of blastomycosis should be treated to prevent extrapulmonary dissemination.⁵⁶ Mild to moderate pulmonary disease can be treated with azole‐based antifungals. Itraconzole for up to 12 months is a common regimen. Moderately severe pulmonary disease should be initially treated with lipid formulation of amphotericin B (AmB) for one to two weeks or until improvement is noted. This is followed by oral itraconazole therapy. Serum levels of itraconazole should be determined after two weeks from the treatment to ensure adequate drug exposure.^56,61 Table 21‐4 details the treatment recommendation for disseminated and CNS blastomycosis according to the current guidelines.⁵⁶

Oral/Facial Considerations

Oral lesions are rarely the primary site of infection. Indeed, most cases of oral involvement demonstrate concomitant pulmonary lesions on chest radiographs. The most common appearance of the oral lesions of blastomycosis is a nonspecific, painless ulcer with indurated borders and verrucous mucosal hyperplasia, often mistaken for SCC.^62–64

Epidemiology

Histoplasmosis is caused by the fungus Histoplasma capsulatum, a dimorphic fungus with both yeast and mycelial forms. Infection results from inhaling dust contaminated with droppings, particularly from infected birds or bats. An African form of this infection is caused by a larger yeast, H. huboisii, which is considered a variant of H. capsulatum.⁶⁵

Histoplasmosis is the most common systemic fungal infection in the United States and presents primarily as pulmonary disease; in endemic areas such as the Mississippi and Ohio River valleys, serologic evidence of previous infection may be found in 60–90% of the population. The incidence of histoplasmosis in adults aged 65 years and older was calculated as 3.4 cases per 100,000 population in the United States in general and 6.1 cases per 100,000 population in the Midwest. Outbreaks of occupationally acquired histoplasmosis have been reported among agricultural workers and laborers in endemic areas. Particularly at risk are individuals working with aerosolized topsoil or dust with bat or bird droppings.^65,66 Symptomatic histoplasmosis is more prevalent among people with immunosuppression. In Latin America, histoplasmosis is one of the most common opportunistic infections among HIV‐infected individuals, leading to a 30% mortality rate.⁶⁵

Clinical Presentation

In many cases primary infection is mild, manifesting as a self‐limiting pulmonary disease that heals to leave mediastinal fibrosis and calcification, which can be identified on chest radiographs. In a small percentage of cases, progressive disease results in cavitation of the lung and widespread dissemination of the organism. Common locations for disseminated disease include the liver, spleen, adrenal glands, intestinal tract, and meninges. Patients with the disseminated form of the disease may develop anemia and leukopenia secondary to bone marrow involvement. Immunosuppressed or myelosuppressed patients are more likely to develop a severe disseminated form of the disease, and disseminated histoplasmosis is one of the infections that characterize AIDS.⁶⁵

Diagnosis

Antigen detection via enzyme immunoassay can be performed in blood, urine, cerebrospinal fluid (CSF), and bronchoalveolar lavage (BAL) samples for rapid diagnosis of disseminated and acute pulmonary histoplasmosis. Clinically, urine histoplasma antigen is commonly used to diagnose invasive infections. Of note is that chronic pulmonary disease can have a low antigen burden, making the test insensitive.⁶⁷ Other possible diagnostic methods are antibody detection via immunodiffusion, and identification of histoplasma DNA via various PCR techniques. It is important to note that there is some cross‐reactivity with Blastomyces infections.^68,69 In disseminated disease, peripheral blood smear may show the organisms engulfed by white blood cells. Sputum fungal culture and bronchoalveolar lavage can also be performed. Histopathology of the involved tissue can demonstrate the characteristic 2–4 μm diameter budding yeast cells (Figure 21‐6).⁷⁰

Treatment

Immunocompromised patients with disseminated histoplasmosis are generally treated with liposomal AmB and/or itraconazole. Patients with moderate to severe disease should initially receive amphotericin‐based therapy. Alternatives to amphotericin and itraconazole include voriconazole and posaconazole.⁷¹ Fluconazole should not be used, as it is not thought to be active against H. capsulatum. Antifungal selection and duration are based on a combination of factors including duration of symptoms and severity of presentation.⁷⁰ Corticosteroids, such as methylprednisolone during the first one to two weeks of the antifungal therapy, should be considered for patients who develop respiratory complications including hypoxema and significant respiratory distress.^70,72 Antifungal therapies and steroids have limited benefit for patents with fibrosing mediastinitis, a rare complication from histoplasmosis.

Oral/Facial Considerations

Oral manifestations of histoplasmosis are most common in patients with disseminated disease (66%). Oral manifestations of histoplasmosis are also common in subacute (31%) and acute (19%) infections.⁵² However, primary oral involvement has also been reported. In one study, 3% of HIV‐positive patients in an endemic area had oral lesions of histoplasmosis, and oral histoplasmosis had been reported as the first sign of AIDS.⁷³ Patients diagnosed with histoplasmosis should be tested for HIV infection and evaluated for disseminated disease.

Oral mucosal lesions begin as an area of erythema that becomes a papule and eventually forms a painful, granulomatous‐appearing ulcer, often with an indurated border, on the gingiva, palate, or tongue. Some lesions can appear fungating. Cervical lymphadenopathy may also be present. The differential diagnosis of oral histoplasmosis includes SCC, other chronic fungal infections, and lymphoma. Ulcers present for weeks or months may represent other lesions of infectious etiology (other deep fungal, mycobacterial, treponemal, or parasitic), traumatic ulcerative granuloma, SCC, lymphoma, or other malignancy.⁷⁴

Epidemiology

Paracoccidioidomycosis is caused by Paracoccidioidomycosis brasiliensis. About 15,000 cases of paracoccidioidomycosis have been reported since 1930. It occurs in South and Central America; however, the majority of cases have been reported in Brazil.^75,76 Paracoccidioidomycosis brasiliensis infections are thought to be due to inhalation of spores from colonized soil and/or wood. Like other dimorphic fungi, paracoccidioidomycosis has both a mold and a yeast form.

Clinical Presentation

Similar to tuberculosis, most patients are asymptomatic after an initial infection. The organism can be dormant within lymph nodes for many years and then reactivate later in life. The disease affects primarily men (15:1 ratio men,women) over 30 years of age. When reactivated, the infection involves primarily the oral mucosa, the lungs, and the skin. Other potential sites of involvement are the gastrointestinal tract, the liver, the bones, the CNS, and the male genitourinary tract. In severe cases, signs and symptoms may mimic those of TB and include fever, weight loss, and productive cough with bloody sputum. Paracoccidioidomycosis can occur in immunocompetent and immunocompromised individuals; however, symptoms usually get worse more quickly in immunocompromised patients such as HIV‐infected subjects.⁷⁷

Diagnosis

Paracoccidioidomycosis can be identified by direct examination of sputum or biopsy from ulcers or pus draining from lymph nodes. A 10% potassium hydroxide (KOH) preparation should be used to observe paracoccidioidomycosis yeasts. The microorganism is then isolated in culture.^78–80

Treatment

The preferred agents to treat paracoccidioidomycosis are azole antifungals, with itraconazole being preferred due to lower relapse rates. AmB is generally avoided in patients with mild or moderate illness due to higher toxicity.⁸¹ Trimethoprim/sulfamethoxazole (cotrimoxazole) is also used for the treatment of paracoccidioidomycosis.⁸² However, patients treated with cotrimoxazole generally require a longer treatment duration.

Oral/Facial Considerations

Oral mucosal lesions are a prominent feature of paracoccidioidomycosis and present as ulcers; oral complaints are often the presenting symptoms of these patients. Lesions of the gingival mucosa are most common, followed by the palate and lips. The lesions are frequently painful. Ulcerative lesions with crusting also occur on the facial skin and may infiltrate subcutaneously.⁸³

Epidemiology

Organisms of the fungal genus Aspergillus cause multiple infections, including invasive aspergillosis, chronic necrotizing aspergillosis, allergic bronchopulmonary aspergillosis, and aspergilloma. Commonly found in soil, on plants, in decaying organic matter, and in dust from houses and building materials, Aspergillus spp. represent a variety of organisms that are ubiquitous in the environment. Colonization of the respiratory tract in humans occurs. Thus, oral medicine clinicians should carefully consider whether a positive Aspergillus culture is compatible with an infection or simply colonization. A. fumigatus complex is generally considered the most pathogenic species.

The epidemiology of Aspergillus infections varies based on disease presentation. Immunocompromised patients, particularly those receiving chemotherapy, classically present with a fungal pneumonia from Aspergillus. In addition to the lungs, invasive aspergillosis can involve the CNS, bones, eyes, heart, and kidneys.^84,85

Clinical Presentation

There are many risk factors that are strongly associated with acquiring invasive aspergillosis, such as allogeneic stem‐cell transplantation, prolonged severe neutropenia (>10 days), immunosuppressive therapy, chronic granulomatous disease, solid organ transplantation, acute leukemia, aplastic anemia, and preexisting cavity (aspergilloma). Moreover, other risk factors weakly associated with increased risk for acquiring invasive aspergillosis include advanced chronic lung disease, primary immunodeficiency, HIV infection, diabetes, cystic fibrosis, severe burns, malnutrition, multiple myeloma, immunocompromised patients, age >55 years, and smoking.⁸⁴

Diagnosis