Candidiasis

Generalized cutaneous candidiasis: This is an unusual form of cutaneous candidiasis that manifests as a diffuse eruption over the trunk, thorax, and extremities. The patient has a history of generalized pruritus, with increased severity in the genitocrural folds, anal region, axillae, hands, and feet. Physical examination reveals a widespread rash that begins as individual vesicles that spread into large confluent areas.

Intertrigo: The patient has a history of intertrigo affecting any site where the skin surfaces are in close proximity, providing a warm and moist environment. Pruritic red rash occurs. Physical examination reveals a rash that begins with vesiculopustules, which enlarge and rupture, causing maceration and fissuring. The area involved has a scalloped border, with a white rim consisting of necrotic epidermis that surrounds the erythematous macerated base. Satellite lesions frequently are found that may coalesce and extend into larger lesions.

Metastatic skin lesions: Characteristic skin lesions occur in about 10% of patients with disseminated candidiasis and candidemia. The lesions may be numerous or few. Lesions are generally described as erythematous, firm, nontender macronodular lesions with discrete borders. Biopsied specimens of these lesions demonstrate yeast cells, hyphae, or pseudohyphae, and cultures are positive for Candida species approximately 50% of the time.

Candida folliculitis: The infection is found predominantly in the hair follicles and rarely can become extensive.

Paronychia and onychomycosis: Frequently, paronychia and onychomycosis are associated with immersion of the hands in water and with diabetes mellitus. The patient has a history of a painful and erythematous area around and underneath the nail and nail bed. Physical examination reveals an area of inflammation that becomes warm, glistening, tense, and erythematous and may extend extensively under the nail. It is associated with secondary nail thickening, ridging, discoloration, and occasional nail loss.

Chronic mucocutaneous candidiasis

Chronic mucocutaneous candidiasis describes a group of Candida infections of the skin, hair, nails, and mucus membranes that tend to have a protracted and persistent course.

History: Most infections begin in infancy or the first 2 decades of life; onset in people older than 30 years is rare. Most patients survive for prolonged periods of time and rarely experience disseminated fungal infections. The most common cause of death is bacterial sepsis.

Chronic mucocutaneous candidiasis frequently is associated with endocrinopathies, such as the following:

Hypoparathyroidism

Addison disease

Hypothyroidism

Diabetes mellitus

Autoimmune antibodies to adrenal, thyroid, and gastric tissues (approximately 50%)

Thymomas

Dental dysplasia

Polyglandular autoimmune disease

Antibodies to melanin-producing cells

Physical examination reveals disfiguring lesions of the face, scalp, hands, and nails. This occasionally is associated with oral thrush and vitiligo.

Gastrointestinal tract candidiasis

Oropharyngeal candidiasis

The patient has a frequent history of using broad-spectrum antibiotics or inhaled steroids or having HIV infection, chemotherapy, dentures, or diabetes mellitus. Variable symptoms include the following:
- Asymptomatic

Physical examination reveals a diffuse erythema and white patches that appear on the surfaces of the buccal mucosa, throat, tongue, and gums. There are 5 types of OPC, which include the following:

Membranous candidiasis is the most common type and tends to have creamy-white curdlike patches on the mucosal surfaces.

Erythematous candidiasis is associated with an erythematous patch on the hard and soft palates.

Chronic atrophic candidiasis (denture stomatitis) is thought to be the most common form of the disease. The presenting signs and symptoms include chronic erythema and edema of the portion of the palate that comes into contact with dentures.

Angular cheilitis is an inflammatory reaction characterized by soreness, erythema, and fissuring at the corners of the mouth.

Esophageal candidiasis

The patient’s history usually includes the use of broad-spectrum antibiotics or inhaled steroids or the presence of HIV infection, chemotherapy, or hematologic or solid organ malignancy. Variable symptoms that include the following:
- Asymptomatic

On physical examination, oral candidiasis nearly always is present.

Nonesophageal gastrointestinal candidiasis

Most commonly, the patient’s history includes an association with neoplastic disease of the GI tract. The stomach is found to be the second most commonly infected site after the esophagus. With less frequency, chronic gastric ulcerations, gastric perforations, and malignant gastric ulcers with concomitant candidal infection may exist. The third most common site of infection (20%) is the small bowel. The frequency of candidal infection in the small bowel is the same as in the large bowel. Approximately 15% of patients develop systemic candidiasis.

Physical examination is variable, and depends on the site of infection. The diagnosis, however, cannot be made solely on culture results because approximately 20-25% of the population is colonized by Candida. The following symptoms may be present:

Epigastric pain

Nausea and vomiting

Abdominal pain

Fever and chills

Occasionally, an abdominal mass is palpated.

Respiratory tract candidiasis

The respiratory tract frequently is colonized with Candida species, especially in hospitalized patients. In ambulatory patients, 20-25% of the population is colonized by Candida species.

Laryngeal candidiasis: This is very unusual but may be a source for disseminated candidiasis. Laryngeal candidiasis primarily is observed in hematologic malignancies. The patient may present with a sore throat and hoarseness. Physical examination generally is unremarkable, and the diagnosis is made by direct or indirect laryngoscopy.

Candida tracheobronchitis: This is a rare form of candidiasis. Most patients with Candida tracheobronchitis are seropositive for HIV or severely immunocompromised, complaining of fever, productive cough, and shortness of breath. Physical examination reveals dyspnea and scattered rhonchi. The diagnosis generally is made during bronchoscopy.

Candida pneumonia: It does not exist alone and occurs only rarely as part of disseminated candidiasis. The most common form is multiple abscesses due to hematogenous dissemination of Candida species. The high degree of colonization and isolation of Candida species from the respiratory tract makes it difficult to make a diagnosis. The patient’s history reveals similar risk factors for disseminated candidiasis, and patients complain of shortness of breath, cough, and respiratory distress. Physical examination reveals fever, dyspnea, and variable breath sounds, from clear to rhonchi to scattered rales.

Genitourinary tract candidiasis

Vulvovaginal candidiasis: This is the second most common cause of vaginitis. The patient’s history includes vulvar pruritus, vaginal discharge, dysuria, and dyspareunia. Approximately 10% of women experience repeated attacks of VVC without precipitating risk factors. Physical examination includes a vagina and labia that usually are erythematous, a thick curdlike discharge, and a normal cervix on speculum examination.

Candida balanitis: Patients complain of itchiness of the penis. Lesions and whitish patches are present. Candida balanitis is acquired through sexual intercourse with a partner who has VVC. Physical examination reveals vesicles on the penis that develop later into patches resembling thrush. The rash may spread to the thighs, gluteal folds, buttocks, and scrotum.

Candida cystitis: Many patients frequently are asymptomatic. However, bladder invasion may result in frequency, urgency, dysuria, hematuria, and suprapubic pain. Candida cystitis may or may not be associated with the use of a Foley catheter. Physical examination may reveal suprapubic pain; otherwise, the examination may be unremarkable.

Asymptomatic candiduria: Most catheterized patients with persistent candiduria are asymptomatic, as noncatheterized patients may be. The majority of patients with candiduria have easily identifiable risk factors for candida colonization. Thus, the distinction between invasive disease and colonization cannot be made solely on culture results because approximately 5-10% of all urine cultures may be positive for Candida.

Ascending pyelonephritis: The use of stents and indwelling devices, along with the presence of diabetes, is the major risk factor predisposing patients to ascending infection. The patient frequently has a history associated with flank pain, abdominal cramps, nausea, vomiting, fever, chills, and hematuria, Physical examination reveals abdominal pain, costovertebral-angle tenderness, and fever.

Fungal balls: This is due to the accumulation of fungal material in the renal pelvis. The condition may produce intermittent urinary tract obstruction, with subsequent anuria and ensuing renal insufficiency.

Hepatosplenic candidiasis

A variety of systemic candidiasis patients have an underlying hematologic malignancy and are in the recovery phase of a prolonged episode of neutropenia. The patient’s history includes the following:

Fever unresponsive to broad-spectrum antimicrobials

Right upper quadrant pain

Abdominal pain and distension

Jaundice (rarely)

Physical examination includes the following:

Right upper quadrant tenderness

Hepatosplenomegaly (<40%)

Systemic candidiasis

Systemic candidiasis can be divided into 2 major categories, which are candidemia and disseminated candidiasis (organ infection by Candida species). Deep organ infections due to Candida species generally are observed as part of the disseminated candidiasis syndromes, which may be associated with either single or multiorgan involvement.

Candidemia

Candida species currently are the fourth most commonly isolated organism in blood cultures, and Candida infection generally is considered a nosocomially acquired infection. The patient’s history commonly will reveal the following:

Fever for several days unresponsive to broad-spectrum antimicrobials, frequently the only marker of infection

Prolonged intravenous catheterization

A history of several key risk factors (see Pathophysiology)

Possibly associated with multiorgan infection

Physical examination is remarkable for the following:

Fever

Macronodular skin lesions (approximately 10%)

Candidal endophthalmitis (approximately 10-28%)

Occasionally, septic shock (hypotension, tachycardia, tachypnea)

Other causes of candidemia without invasive disease include the following:

Intravascular catheter-related candidiasis: This entity usually responds promptly to catheter removal and antifungal treatment.

Suppurative thrombophlebitis: This for the most part is observed secondary to prolonged central venous catheterization. Suppurative thrombophlebitis is manifested by fever and candidemia, which persists despite antifungal therapy and catheter removal. Sepsis also may be present.

Endocarditis: The frequency of endocarditis has increased in the past few years. Endocarditis is the most common cause of fungal endocarditis and is primarily due to Candida albicans (>60% of cases). The most common valves involved are the aortic and mitral. Two different forms of endocarditis exist—exogenous, which is secondary to direct infection during surgery, and endogenous, which is due to secondary spread during candidemia and disseminated candidiasis. Endocarditis frequently is associated with 4 main risk factors, which are the following: (1) intravenous heroin use, which frequently is associated with infection due to Candida parapsilosis, (2) chemotherapy, (3) prosthetic valves (approximately 50%), and (4) prolonged use of central venous catheters.

Physical examination in endocarditis reveals a broad range of manifestations, which include the following: fever unresponsive to antimicrobials, hypotension, shock, new or changing murmurs, and large septic emboli to major organs, a characteristic of fungal endocarditis.

Disseminated candidiasis: This frequently is associated with multiple deep organ infections or may involve single organ infection. Unfortunately, of patients with disseminated candidiasis, as many as 40-60% may have blood cultures negative for Candida species. The history of a patient with presumptive disseminated candidiasis reveals a fever unresponsive to broad-spectrum antimicrobials and negative results on blood culture. Physical examination reveals fever (may be the only symptom) with an unknown source and sepsis and septic shock.

Candida endophthalmitis: Two forms of Candida endophthalmitis exist. Exogenous endophthalmitis is associated with either accidental or iatrogenic (postoperative) injury of the eye and the inoculation of the organism from the environment. Endogenous endophthalmitis results from hematogenous seeding of the eye. It is found in 10-28% of patients with candidemia. The use of hematogenous candidal endophthalmitis as a marker of widespread disseminated candidiasis is important.

The patient’s history reveals a broad range of manifestations.
- Eye injury

Physical examination reveals the following:

Fever

On funduscopic examination, early lesions are the size of a pinhead, off-white in color, and found in the posterior vitreous with distinct margins and minimal vitreous haze.

On funduscopic examination, classic lesions are large and off-white, like a cotton-ball with indistinct borders covered by an underlying haze. Lesions are 3-dimensional and extend into the vitreous off the chorioretinal surface. They may be single or multiple.

Renal candidiasis

This most frequently is a consequence of candidemia and disseminated candidiasis. The patient history reveals the following:
- Fever unresponsive to broad-spectrum antimicrobials

Physical examination generally is unremarkable, and renal candidiasis is diagnosed on urinalysis and renal biopsy.

CNS infections due to Candida species
- CNS infections due to Candida species are rare, difficult to diagnose, and 2 primary forms exist—exogenous and endogenous infection. Exogenous infection is due to postoperative infection, trauma, lumbar puncture, and shunt placement. Endogenous infection is due to candidemia, thus involving the brain parenchyma and multiple small abscesses, eg, disseminated candidiasis.

Candida arthritis, osteomyelitis, costochondritis, and myositis
- Musculoskeletal infections were rare; currently, they are more common because of the increased frequency of candidemia and disseminated candidiasis. The most common sites of involvement are the knee and vertebral column. The pattern of involvement is similar to the pattern observed in bacterial infections. In addition, 2 forms exist—exogenous and endogenous infection. The exogenous infection frequently is due to direct inoculation of the organisms, such as postoperative infection or trauma.
  - Ribs and leg bones (<20 y)

Myocarditis-pericarditis: This is due to hematogenous spread in association with disseminated disease and rarely is due to direct extension from the sternum or esophagus. Myocarditis-pericarditis occurs as diffuse abscesses scattered throughout the myocardium with normal cardiac tissue. In disseminated candidiasis, the incidence has been documented to be as high as 50%. The patient history reveals serious complications in 10-20% of cases without valve disease and fever and chills. Physical examination reveals fever, hypotension, shock, tachycardia, and new murmurs or rubs (changes in previously detected murmurs).

Candida peritonitis

The patient history frequently reveals an association with GI tract surgery, viscous perforation, or peritoneal dialysis. Candida peritonitis tends to remain localized, and only 15% of cases may disseminate into the blood stream. A broad range of manifestations exists, including fever and chills, abdominal pain and cramping, nausea and vomiting, and constipation.

Physical examination is significant for the following:

Fever

Abdominal distention

Abdominal pain

Absent bowel sounds

Rebound tenderness

Localized mass

Candida splenic abscess and hypersplenism: Both are manifestations of disseminated candidiasis and usually are associated with liver involvement simultaneously. Manifestations of hypersplenism are observed frequently (see Hepatosplenic candidiasis).

Candida cholecystitis: This is rare and generally is associated with bacterial cholangitis and ascending cholangitis. Most of the time, Candida cholecystitis is diagnosed at the time of surgery when a culture is obtained.

Physical: See History for physical examination findings paired with clinical syndromes.

Causes: More than 100 species of Candida exist in nature; only a few species are recognized as causing disease in humans.

The medically significant Candida species include the following:

C albicans, the most common species identified (50-60%)

Candida glabrata (15-20%)

Candida parapsilosis (10-20%)

Candida tropicalis (6-12%)

Candida krusei (1-3%)

Candida kefyr (<5%)

Candida guilliermondi (<5%)

Candida lusitaniae (<5%)

Candida dubliniensis, primarily recovered from patients who are positive for HIV (>95%)

C glabrata and C albicans account for approximately 70-80% of yeast isolated from patients with invasive candidiasis. C glabrata recently has become important because of its increasing incidence worldwide, and it is intrinsically less susceptible to azoles and amphotericin B.

Some Candida species, C lusitaniae, C krusei, and C guilliermondi, are important because of their resistance to fluconazole.

Another important Candida species is C krusei; although not as common as some Candida species, it is of clinical significance because of its intrinsic resistance to fluconazole, and it is less susceptible to all other antifungals, including amphotericin B.