Clinical Features

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.

Oral Manifestations

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.

Histologic Features

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.

Oral Manifestations

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.

Clinical Features

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.

Oral Manifestations

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.

Histologic Features

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).

Treatment

Pulmonary histoplasmosis usually, resolves spontaneously, while severe forms of the disease are usually treated by amphotericin B.

Clinical Features

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.

Oral Manifestations

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.

Histologic Features

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.

Treatment

Amphotericin B has been found to provide effective chemotherapeutic control of the disease.

Clinical Features

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.

Cryptococcosis has been repeatedly reported in patients already suffering from some form of malignant lymphoma, evidence of the opportunistic nature of the disease.

Oral Manifestations

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).

Histologic Features

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.

Treatment and Prognosis

The use of amphotericin B has been found to give excellent results. The ultimate prognosis of the patient is variable; however, and especially dependent upon the sites of involvement.