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Two cases of primary and isolated gastroduodenal candidiasis are described. The diagnosis of the mycotic infection was based on the discovery of hyphae in the biopsy obtained through the gastroscope (Olympus GIF-K). Clinical, endoscopic and histologic appearances are discussed.
A radioimmunoassay (RIA) that detects candida mannan was developed so that immunodiagnosis of systemic candidiasis could be improved. The RIA was evaluated in an animal model of disseminated disease and in a panel of patient sera. Mannan antigenemia was detected with the RIA in 52% of 29 rabbits with systemic candidasis, but not in 60 normal rabbits or 31 rabbits with systemic aspergillosis. In an evaluation of human sera, mannan antigenemia was detected in five of 11 patients with systemic candidiasis, one of three patients with invasive gastrointestinal candidiasis, and one patient with a sustained candidemia associated with an infected intravenous catheter. Mannan was not detected in sera from 11 patients with superficial candida infections, seven patients colonized with Candida, three patients with chronic mucocutaneous candidiasis, eight patients with other systemic mycoses, or 22 normal donors. This study demonstrates the utility of this RIA for early, specific immunodiagnosis of invasive candidiasis.
We have followed the candida antibody response in 115 patients with different types of candidiasis by discontinuous counterimmunoelectrophoresis using HS antigen to learn whether any early antibody response occurs in systemic candidiasis and whether there are differences in the antibody response in candidiasis involving different organ systems. We found that 23 of 32 (72%) patients with systemic candidiasis had a rise in antibody titer within the first 2 weeks of infection and that high titers were relatively insensitive indicators of infection. No differences were seen in the antibody response in different types of candidiasis. Patients with aspergillosis and torulopsosis had titer rises as well which were attributed to either inapparent candida infection or cross-reacting antibody. A rise in titer was not seen in any patient with candida colonization, bacterial or viral infection, or no infection in contrast to titers greater than or equal to 1/1 or greater than or equal to 1/8 which were seen in these conditions.
Histologically proven infection of the heart by Candida organisms occurred in 17 (10%) of 168 cancer patients with candidiasis studied at necropsy. All 17 patients were among the 85 patients with disseminated Candida infection; none of the 83 patients with localized candidiasis had involvement of the heart. Abscesses in the myocardium were present by histologic examination in all 17 patients and in 8 were evident on gross inspection as well. The mural endocardium was also affected in 5 patients from direct extension of a myocardial abscess. The valves were uninvolved. Pericardial infection was detected in 2 patients. The 17 patients with cardiac Candida infection had a higher frequency of positive premortem blood and cerebrospinal fluid cultures and of presence of Candida in the heart's blood than did the 68 patients with disseminated candidiasis but without involvement of the heart. Symptoms or signs of cardiac dysfunction resulting from the cardiac Candida infection were not readily detected in any patient. The clinical and pathologic features of cardiac candidiasis in cancer patients are distinct from those observed in Candida endocarditis.
The clinical, pathologic and immunologic features of 27 patients with chronic mucocutaneous candidiasis and thymic tumors are reviewed. This form of chronic candidiasis is unique in that the infections do not occur until after the third decade and, in contrast to patients in whom candidiasis develops during infancy or childhood, it is not accompanied by failure of endocrine organs. Instead, the patients have the disorders that often accompany thymoma, such as myasthenia gravis, hypogammaglobulinemia, and abnormalities of the bone marrow and circulating blood elements. Evidence of impaired cell-mediated immunity was found in 16 of the 21 patients in whom studies were made. The pathogenesis of the immunodeficiency in these patients is unknown. Immunosuppressive activities in the plasma of four patients were found, but none of the five patients in whom the appropriate studies were made was found to have suppressor cells. The features of this disorder are unique enough that it should be considered a syndrome, and patients in whom candidiasis develops during their adult years should be studied for the presence of thymoma.
Systemic candidiasis has emerged as a major cause of death in burn patients. An increase both in the incidence of systemic candidiasis and its increase as a cause of death has been observed. Treatment with systemic amphotericin-B prior to 1971 at our institution was rarely successful. This was felt to be in part due to lack of sufficiently early recognition of the infection and to delay in the initiation of appropriate systemic therapy. From 1971 to 1975, fifteen patients have been treated with systemic amphotericin-B with one death. There have been no fatalities from candidiasis since 1972. No serious complications attributed to the use of amphotericin-B were observed. Prompt initiation of therapy with intravenous amphotericin-B is advised for burn patients in whom systemic candidiasis is present.
Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals. Although mucocutaneous candidiasis is generally not life-threatening, it can cause considerable discomfort, recurrent infections, and complications, particularly in patients with underlying conditions such as diabetes or in those taking immunosuppressive therapies. The rise of difficult-to-treat Candida infections is driven by new host factors and antifungal resistance. Pathogens, such as Candida auris (Candidozyma auris) and fluconazole-resistant Candida parapsilosis, pose serious global health risks. Recent taxonomic revisions have reclassified several Candida spp, potentially causing confusion in clinical practice. Current management guidelines are limited in scope, with poor coverage of emerging pathogens and new treatment options. In this Review, we provide updated recommendations for managing Candida infections, with detailed evidence summaries available in the appendix.
In a review of 2,616 consecutive autopsies done at the University of Kentucky Medical Center over a 12-year period, 46 patients with complete postmortem examinations had tissue-verified candidiasis in two distinct patterns, with Candida albicans being most frequently cultured. Superficial candidiasis involving only lining surfaces was observed in 21 patients (46%). Usually, it complicated other lethal problems such as malignancy and bacterial sepsis. Nineteen of these patients (95%) had received antibiotics. No vessel invasion or deep organ involvement was evident in this group. The other pattern of candidiasis was a deep or systemic variety recognized in the remaining 25 patients (54%). It was characterized by deep parenchymal organ lesions usually involving the brain (52%), heart (48%), and kidney (80%), but any tissue seemed susceptible. Vessel invasion was seen in 8 patients (32%); intravenous lines were used in 13 (52%); and major operations were done in 16 (64%). All these patients were hospitalized for either benign or malignant conditions and were treated for bacterial sepsis with antibiotics for seven days or more. This investigation indicates that candidiasis occurs when the host's environment is altered primarily by antibiotic therapy. Candida then can colonize lining surfaces and from there could invade adjacent vessels and disseminate throughout the body.
Three hundred fifty human sera were tested by double immunodiffusion, crossed-line electrophoresis, and crossed immuno-affinoelectrophoresis with a concanavalin A intermediate gel for precipitating antibodies to antigens present in cytoplasmic extracts of Candida albicans. Sera from 48 of 287 hospitalized patients at risk of invasive candidiasis contained precipitating antibodies to Candida antigens. Of these 48 sera, 27 had precipitating antibodies only to cell-wall antigens present in the cytoplasmic extract, and 21 sera had precipitating antibodies to both cytoplasmic and cell-wall antigens. The latter sera came from patients who were 2.5 times as likely to have deep-seated candidiasis as those patients with precipitins exclusively to cell-wall antigens. Sera from seven of 22 patients with vaginal candidiasis and 10 of 41 patients with other fungal infections had precipitating antibodies to C. albicans cell-wall antigens; only two of these sera also contained precipitating antibodies to the cytoplasmic antigens. Crossed immunoaffinoelectrophoresis with concanavalin A reduced the number of false-positive results and increased the predictive value positive of the precipitin test for deep-seated candidiasis from 31% to 71%.
Because of the difficulty in diagnosis of invasive candidiasis, an assay that makes use of counterimmunoelectrophoresis (CIE) was developed to detect candida antigen. A cell-wall polysaccharide of Candida was extracted with hot formamide, ethanol precipitation, and gel filtration. Rabbit antiserum was tested by CIE against sera from 20 healthy individuals, 15 patients with mucosal candidiasis, and 48 compromised patients with cultures positive for Candida. Antigen was detected in sera from 13 patients by CIE; eight of these patients were eventually proven to have invasive disease. None of the antigen-negative patients for whom autopsy was performed had evidence of invasive candidiasis. Healthy individuals and patients with superficial mucosal candidiasis were also antigen-negative. The detection of candida antigenemia by CIE is specific for invasive disease and serves as a guide in initiation and follow through of antifungal therapy.
Serum antibody titers to Candida albicans were estimated in 37 women with recurrent vaginal candidiasis and in 148 normal American and Finnish subjects, using the passive-hemagglutination technique. The antibody titers ranged from 0 to 16 in normal individuals and 4 to 256 in vaginal candidiasis patients. Antibodies to C. albicans in the sera of vaginal candidiasis patients were found to be the secretory immunoglobulin A type, as determined by gel filtration and double-diffusion tests. The results were confirmed by the indir-ct fluorescent-antibody technique. Our findings suggest that, in vaginal candidiasis, the antibody response is mainly local, consisting of secretory immunoglobulin A, some of which finds its way into systemic circulation.
A total of 37 serum samples from 27 cancer patients were tested by an enzyme-linked immunosorbent assay-inhibition technique for the detection of Candida antigen. In 20 randomly chosen sera from patients without clinical evidence of candidiasis and in 10 sera from patients proven by autopsy not to have candidiasis, the inhibition ranged up to 17%; in contrast, inhibition ranged from 22 to 56% in all seven patients proven by autopsy to have systemic candidiasis, indicating the presence of Candida antigen in the sera of these patients. This technique appears promising in diagnosing disseminated candidiasis in cancer patients.
Clotrimazole was administered in the form of 100 mg tablets to patients with vaginal candidiasis, and in the form of a 1% solution to patients with cutaneous candidiasis of the genital and perigenital areas. The clinical and mycological response observed and the excellent tolerance and lack of side effects indicate that clotrimazole may be proposed as a treatment for candidiasis.
Disseminated candidiasis was clinically diagnosed by muscle and skin biopsies in two patients with hematologic malignancies. One patient with acute promyelocytic leukemia presented with skin lesions as the sole manifestation of disseminated candidiasis. The other patient had leukemic reticuloendotheliosis and developed fever, severe myalgias, and maculopapular rash while receiving corticosteroid therapy; this patient is the first to have antemortem documentation of candida myositis as the initial manifestation of disseminated candidiasis. These two case reports serve to emphasize the importance of careful observation and early biopsy of skin and muscle to establish the diagnosis and permit early institution of therapy.
The diagnosis of pulmonary candidiasis can only be made with certainty when tissue invasion by the organism is demonstrated histologically. In order to ascertain whether characteristic radiographic patterns are seen in patients with pulmonary candidiasis, antemortem radiographic abnormalities were correlated with autopsy findings in 25 immunosuppressed patients who had histoinvasive pulmonary candidiasis. Pathological analysis enabled division of patients by route of infection into hematogenous and endobronchial groups, characterized by disseminated nodules and patchy bronchopneumonia, respectively. However, no specific radiographic patterns emerged in either patient group due to the small size of lesions and the high frequency of other pulmonary infections, edema, and hemorrhage. Since the radiographic patterns described for other opportunistic fungi do not appear to apply to this organism, a decision to institute antifungal therapy should not await evolution of radiographic changes.
Rabbits were employed as experimental models to evaluate a solid-phase radioimmunoassay (RIA) method for the diagnosis of systemic candidiasis. Ten rabbits were inoculated subcutaneously to mimic superficial candidiasis and were found to produce no antibodies to Candida as determined by both immunodiffusion and RIA procedures. However, 94 per cent of 18 rabbits systemically infected by intravenous injection of Candida cells were observed to produce antibody as assessed by the RIA technique. These data encourage further tests with human sera and the continued development ofthis RIA procedure as a useful tool in the early serodiagnosis of systemic candidiasis.
A 2.5 kg thoracopagus (Siamese) twin and a 0.73 kg premature newborn developed systemic candidiasis and were treated with intravenous miconazole. The conjoined twin was in a state of severe metabolic acidosis, respiratory distress, jaundice, anuria, abdominal distension, and shock. The 0.73 kg premature infant was also in a state of severe metabolic acidosis, respiratory distress, and oliguria. Miconazole was used in this desperate situation for the treatment of life-threatening candidiasis. Both infants responded well to treatment and recovered. All parameters of their diseases improved during therapy despite pre-existing multiple organ dysfunction. Miconazole can be a safe alternative to amphotericin B for the treatment of systemic candidiasis in neonatal infants, including those with impaired renal function.
Twenty patients with chronic oral candidiasis were assigned by random allocation to a two-week course of either 10-mg clotrimazole buccal troches or placebo taken five times daily in a double-blind clinical trial. Each of the 10 recipients of clotrimazole had marked regression of symptoms and mucosal lesions, and in nine patients potassium hydroxide preparations and cultures of mucosal scrapings gave no evidence of candidiasis. In contrast, only one of the 10 patients receiving placebo showed any improvement. The clinical outcome in the clotrimazole-treated group was significantly more favorable (P less than 0.001) than in the group receiving placebo. No adverse reactions to the drug were observed. After the blind phase of their trial, 15 patients were treated with clotrimazole troches in an open trial. One to three troches per day were found adequate to sustain remissions. We conclude that clotrimazole is highly effective treatment for chronic oral candidiasis.