Mycotic Infections of the Oral Cavity
Mycology, the study of fungal infections, has gained remarkable impetus in the past few decades, owing at least in part to the fact that fungal diseases are far more common than was previously suspected. Many erroneous conceptions of this branch of microbiology existed until only recently, but careful scientific investigation of various aspects of mycology, such as epidemiology, pathogenesis, immunology, diagnosis and treatment, has done much to eliminate the confusion. Furthermore, excellent monographs and reviews on certain fungal diseases, such as those on blastomycosis by Witorsch and Utz and by Sarosi and Davies; on coccidioidomycosis by Fiese and by Stevens; on cryptococcosis by Littman and Zimmerman; on histoplasmosis by Sweany and by Goodwin and his colleagues; and on mucormycosis (phycomycosis) by Lehner, have been valuable contributions to our understanding of these conditions.
North American blastomycosis is a mycotic infection caused by Blastomyces dermatitidis and may occur either in a cutaneous form or in a systemic form involving bones, liver, lungs, subcutaneous tissues, and other organs. Experimental transmission to animals is only haphazardly successful and cannot be used as an aid in diagnosis, although spontaneous infection in dogs is quite common. The source of the infection in human beings is unknown, although affected persons commonly work or spend a great deal of time outdoors. It is becoming an important medical problem, particularly in central United States as has been pointed out by Furcolow and his associates.
North American blastomycosis is far more common in men than in women and typically occurs in middle age. Skin lesions usually begin as small red papules which gradually increase in size and form tiny miliary abscesses or pustules which may ulcerate to discharge the pus through a tiny sinus. Crateriform lesions are typical and these often exhibit indurated and elevated borders (Figs. 7-1, 7-2). The infection commonly spreads through the subcutaneous tissues and becomes disseminated through the blood stream. The systemic disease is characterized by fever, sudden weight loss, and in cases of lung involvement, a productive cough associated with other symptoms typical of pulmonary tuberculosis.
Lesions of the oral cavity have been reported occurring in blastomycosis and may resemble those of actinomycosis, although abscess formation is not usually as prominent. Tiny ulcers may be the chief feature. The oral infection may be either the primary lesion or secondary to lesions elsewhere in the body. In an extensive discussion of this disease, Witorsch and Utz have reported that 25% of their group of patients had oral or nasal mucosal lesions. Bell and his coworkers have also pointed out that the oral lesions, which may be the first apparent manifestation of the disease, are probably more common than has been thought. In two cases reported by Page and his associates, the oral lesions bore enough resemblance to epidermoid carcinoma to warrant it as a consideration in the differential diagnosis.
The microscopic features of North American blastomycosis are similar to those of other chronic granulomatous infections. The inflamed connective tissue shows occasional giant cells and macrophages and the typical round organisms, often budding, which appear to have a doubly refractile capsule (Fig. 7-2). The organisms, usually measuring between 5μ and 15μ in diameter, are common within giant cells. Microabscesses are frequently found. If the lesions are not ulcerated, overlying pseudoepitheliomatous hyperplasia may be prominent.
South American blastomycosis is related to the North American form of the disease and is caused by infection with Blastomyces (Paracoccidioides) brasiliensis. The systemic lesions are similar to those of North American blastomycosis.
Bogliolo reported that the organisms may enter the body through the periodontal tissues and subsequently reach the regional lymph nodes, producing a severe lymphadenopathy. He has demonstrated the organisms in both the periodontal membrane and in a periapical granuloma and has cultivated them from these sites. The microorganisms also have been shown to penetrate the tissues and establish infection after extraction of teeth, producing papillary lesions of the oral mucosa. Widespread oral ulceration is also a common finding.
The chief difference between North American and South American blastomycosis is in the size of the causative organisms. The fungus in the South American form of the disease varies between approximately 10μ and 60μ in diameter, being considerably larger than that of the North American disease.
Histoplasmosis is a generalized fungal infection caused by the organism Histoplasma capsulatum. It is widespread in its distribution and endemic in the Mississippi Valley and Northeastern United States, where up to 75% of the population have had a primary but subclinical infection. It is usually acquired by inhalation of dust containing spores of the fungus, the contamination probably occurring from excreta of birds such as pigeons, starlings, and blackbirds. It is classified clinically into acute primary pulmonary, chronic pulmonary and disseminated forms. In the disseminated forms, the infection spreads to extra pulmonary sites including oral cavity.
Oral lesions are present in a high percentage of cases. Reports of 73 cases have been reviewed by Weed and Parkhill, which found that 33% of the cases had oral lesions as part of the presenting complaint.
The disease is characterized by a chronic low-grade fever, productive cough, splenomegaly, hepatomegaly and lymphadenopathy, since the organisms have a special predilection for the reticuloendothelial system and chiefly involve the spleen, liver, lymph nodes, and bone marrow. Anemia and leukopenia may also be present. The infection by this organism may be extremely mild, manifesting only local lesions such as subcutaneous nodules or suppurative arthritis, and may produce no more serious effects than a positive histoplasmin skin reaction or calcified pulmonary nodules similar to those seen in tuberculosis. Histoplasmosis often terminates fatally; however, particularly the generalized form.
The oral lesions of histoplasmosis have been reviewed by Levy and by Stiff. They appear as nodular, ulcerative or vegetative lesions on the buccal mucosa, gingiva, tongue, palate, or lips (Fig. 7-3). The ulcerated areas are usually covered by a nonspecific gray membrane which is indurated with raised and rolled out borders resembling carcinoma. The organisms may be demonstrated in tissue sections in many, but not all cases. Thus it is wise in suspected cases to preserve a piece of tissue at the time of biopsy for microbiologic examination. The organism may be readily isolated by inoculating the emulsified tissue onto blood agar containing penicillin and streptomycin. Occasionally cases have been mistaken for carcinoma or even Vincent’s infection, while the lymphadenopathy has suggested Hodgkin’s disease.
Histoplasmosis appears basically to be a granulomatous infection which affects chiefly the reticuloendothelial system. Thus the organisms are found in large numbers in phagocytic cells and appear as tiny intracellular structures measuring little more than 1μ in diameter (Fig. 7-3).
Coccidioidomycosis is now recognized as a relatively common fungal disease and endemic chiefly in the Southwestern portion of the United States, Arizona, California, Nevada, New Mexico, Texas, and Utah. It is also known to occur in Mexico, Central and South America, and occasionally Europe. In those areas where the disease is endemic, the vast majority of the population has at one time or another been infected by the organism, but usually this has been a subclinical infection. The disease appears to be transmitted to man and animals by inhalation of dust contaminated by the spores of the causative organism, Coccidioides immitis. This organism develops from an arthrospore into a nonbudding spherule, measuring between 10μ and 80μ in diameter, which is packed with endospores measuring approximately 5μ in diameter. When the spherules rupture, the endospores which are set free then develop into full-size spherules
There are two basic forms of the disease: primary nondisseminated and progressive disseminated coccidioidomycosis. In primary coccidioidomycosis, patients generally develop manifestations suggestive of a respiratory disease such as cough, pleural pain, headache, and anorexia. In addition, about 20% of the patients develop skin lesions, either erythema nodosum or erythema multiforme. This form of the disease is self-limiting and runs its course within 10-14 days. In a small percentage of cases, pulmonary cavitation, calcified nodules or pulmonary fibrosis may remain.
In the disseminated form of the disease that occurs in only about 1% of the cases, there is a mortality rate of approximately 50%. The disease usually runs a rapid course and the dissemination extends from the lung to various viscera, bones, joints, skin, and to the central nervous system where meningitis is the most frequent cause of death. The dissemination to bone results in osteomyelitis in 10–50% of cases.
Lesions of the head and neck, including the oral cavity, occur with some frequency as has been pointed out by Frauenfelder and Schwartz. The lesions of the oral mucosa and skin are proliferative granulomatous and ulcerated lesions that are nonspecific in their clinical appearance. These lesions tend to heal by hyalinization and scar. Marked chronicity is often a feature of these lesions. Lytic lesions of the jaws may also occur and such a case has been reported by Igo and his associates.
The tissue reaction in coccidioidomycosis is similar to that of many specific infectious granulomas. Large mononuclear cells, lymphocytes and plasma cells predominate, although epithelioid cells are not usually seen. Foci of coagulation necrosis are often found in the center of the small granulomas, and multinucleated giant cells are scattered throughout the lesion. The organisms themselves are often found within the cytoplasm of the giant cells as well as lying free in the tissue. In tissue sections, the organisms will be found to vary greatly in size and generally show no budding. The endospores within the large spherules can usually be identified without difficulty.
Cryptococcosis is a chronic fungal infection caused by Cryptococcus neoformans (Torula histolytica) and Cryptococcus bacillispora, and may present widespread lesions in the skin, oral mucosa, subcutaneous tissues, lungs, joints, and particularly the meninges. The organisms are widespread and frequently found on the skin of healthy persons; for this reason, the exact mechanism of infection is not known. The organisms appear to be harbored by pigeons, but the actual infection of the human probably results from inhalation of airborne microorganisms. Since it is often an opportunistic infection, the disease has increased in incidence as immunosuppression has become more prevalent.
The first evidence of infection by these organisms is the presence of skin lesions from which blood stream dissemination to other parts of the body frequently occurs. Nevertheless, some authorities consider the respiratory tract colonization or visceral lesions to be the primary site, the skin lesions occurring secondarily. The skin lesions appear as multiple brown papules which ultimately ulcerate; the clinical picture is not specific. Most studies indicate a slight predilection for occurrence in middle-aged males.
The lesions of the lungs produce symptoms of a nonspecific pneumonitis, while the meningeal lesions produce a variety of neurologic signs and symptoms generally associated with increased intracranial pressure.
Occasional cases of oral cryptococcosis, almost invariably occurring in patients with other visceral or cutaneous lesions have been reported. One of these reports was that of Newman and Rosenbaum, in which the oral lesions were the first evidence of the infection. Interestingly, their patient was also suffering from chronic lymphatic leukemia.
The oral lesions appear as simply nonspecific single or multiple ulcers, which in a patient known to have leukemia, may be mistaken for the widespread ulceration often seen in leukemic patients as a result of their inability to react to a mild, nonspecific bacterial infection (Fig. 7-4A).
The causative organism is a gram-positive, budding, yeast-like cell with an extremely thick, gelatinous capsule. The Cryptococcus measures 5–20μ in diameter, and in tissue sections, appears as a small organism with a large clear halo, sometimes described as ‘tissue microcyst’ (Fig. 7-4B). The capsule is colored intensely with the periodic acid-Schiff (PAS) stain, and the organisms may be cultured on Sabouraud’s glucose agar.
The tissue reaction is essentially a granulomatous one of the tuberculoid type, but focal necrosis is often absent and epithelioid cell proliferation is minimal. Multinucleated giant cells are common as the organisms with their characteristic halos are found singly or in groups scattered throughout the granuloma.
Candidiasis is caused by a yeast-like fungus, Candida (Monilia) albicans. Although other species, such as C. tropicalis, C. parapsilosis, C. stellatoidea, and C. krusei. C. guilliermondii, C. dubliniensis, and C. glabrata may also be involved.
Candida exists in three forms namely, pseudohyphae, yeast, and chlamydospore forms. It reproduces by asexual budding and forms pseudohyphae. These species grow rapidly at 25–37°C. In general, candida species differ from one another but can be identified by the formation of pseudohyphae or by biochemical test.
It has been shown repeatedly that this microorganism is a relatively common inhabitant of the oral cavity, gastrointestinal tract, and vagina of clinically normal persons. When the favorable condition develops, the organism transforms into pathogenic form, that is yeast form transformed into hyphae. Thus it appears that the mere presence of the fungus is not sufficient to produce the disease. There must be actual penetration of the tissues, although such invasion is usually superficial and occurs only under certain circumstances. This disease is said to be the most opportunistic infection in the world. Its occurrence has increased remarkably since the prevalent use of antibiotics, which destroy the normally inhibitory bacterial flora and immunosuppressive drugs, particularly corticosteroids and cytotoxic drugs. This is the chief cause of this disease in patients with leukemia, lymphoma or other tumors. In addition to affecting the oral cavity, monilial infection frequently involves the skin as well as the gastrointestinal tract, vaginal tract, urinary tract, and lungs. Vaginal colonization appears to be increased by diabetes, pregnancy, and oral contraceptive agents. The incidence of oral candidiasis has increased after the advent of human immunodeficiency virus. It is reported that more than 90% of the HIV infected individuals develop oral candidiasis during some part of their disease (Ellepola ANB and Samaranayake LP, 2000). Oral candidiasis, usually remains a localized disease, but on occasion it may show extension to t/>