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We have described diffuse pulmonary blastomycosis in a previously healthy 19-year-old man, which resulted in the adult respiratory distress syndrome (ARDS). Physicians must have a high index of suspicion for treatable causes of ARDS, and the use of open lung biopsy for early diagnosis is stressed.
We have described a patient with cavitary pulmonary fungal infection, probably blastomycosis, with necrotizing arteritis of the skin. The pulmonary and skin lesions resolved with amphotericin B therapy.
The mechanism of infection in South American blastomycosis is discussed, and the probability of a mild or asymptomatic form of the disease, regressing spontaneously with subsequent immunity, in persons living in endemic areas. Primary lesions in the oral mucosa or in the skin have not been convincingly shown to occur in paracoccidioidomycosis. Several reports of systemic involvement of many organs with no evidence of skin and mucosal lesions support the theory of pulmonary entry.
Keloidal blastomycosis (Lobo's disease) is reported in a 34-year-old man from the Brazilian Amazon area. His left ear and posterior auricular region were involved. He is the eighth of 99 patients known to have lymph node involvement.
A 53-year-old Negro man had North American blastomycosis with acute onset of widespread pustular eruptions. Several tests suggested that the patient might have had a deficiency of delayed hypersensitivity.
A 58-year-old Panamanian man had diagnosis of keliodal blastomycosis (Lobo's disease) by the scarring nodules on his ears and the fungi seen on histologic section.
Blastomyces dermatitidis yeast lysate antigen (T-58, dog isolate) fractions prepared using the Rotofor preparative isoelectric focusing (IEF) cell (Bio-Rad) were compared with B. dermatitidis yeast lysate and filtrate reagents with respect to the detection of antibodies in sera from dogs with blastomycosis, histoplasmosis, coccidioidomycosis, cryptococcosis and aspergillosis. A horseradish peroxidase enzyme immunoassay with Turbo TMB substrate was used in the study. One particular IEF fraction (pH 4.3) was optimal in the assay, and it exhibited greater sensitivity (100%) and specificity (93%) than the lysate or filtrate preparations. The highest degree of cross-reactivity was encountered with the histoplasmosis and coccidioidomycosis specimens and considerably less with the cryptococcosis and aspergillosis sera. Studies are in progress to purify further the optimal IEF fraction.
The case of a 63-year-old carpenter with cutaneous blastomycosis is presented. The patient contracted the disease in 1974 when his leg was injured by a piece of rotten wood during repair works in deep cellars in Lublin's Old Town. Six months later a nodular lesion extending peripherally with hyperkeratosis developed at the site of the injury. The lesions slowly spread to cover more than half of the skin surface of the body. Some of them had regressed spontaneously, leaving cicatrization. Initially, anti-inflammatory treatment was given. Ten years later, in 1984, antimycotic therapy with various antifungal agents was instituted. Improvement appeared to be greatest with fluconazole treatment.
Blastomycosis-like pyoderma is an uncommon reaction pattern to a superficial bacterial infection in persons with a variety of predisposing conditions such as chronic ethanol use and poor nutrition. We are reporting a case that initially responded poorly to previously described treatment regimens but responded well to combination treatment with carbon dioxide laser debridement and long-term minocycline.
We studied the efficacy of new experimental antifungal drugs, which represent molecular modifications of present active agents, in a murine model of blastomycosis. Ketoconazole, previously the best azole drug studied and which is protective when administered orally, was superior to a new oral imidazole, Bay l 9139, and a new oral triazole, Bay n 7133. A new oral triazole, ICI 153066, was markedly more effective than ketoconazole and is the only oral drug studied which came close to producing complete sterilization of all visceral infection in all animals treated. Amphotericin B, a polyene given parenterally, was shown to be more efficacious than any drug studied. It completely sterilized the infection. A modified polyene, N-D-ornithyl amphotericin methyl ester, was only slightly less effective on a milligram-per-kilogram basis.
ICI 195,739, a novel orally active triazole, proved 50 times as potent as ketoconazole, produced a clinical cure, and completely eradicated residual infection in a murine model of pulmonary blastomycosis. No other previously tested azole has shown similar activity. Fungicidal activity against Blastomyces dermatitidis was seen in vitro at concentrations 1/40 of those achieved in serum with protective doses.
The susceptibility of inbred strains of mice to pulmonary blastomycosis was studied to derive information relevant to host resistance and genetic background. Initial studies with eight strains with various H-2 backgrounds revealed the C3H/HeJ strain to be highly susceptible and DBA/1J mice to be resistant. These observations were confirmed with various challenge inocula. These differences were not dependent on the size of the challenge, the strain of Blastomyces dermatitidis, host age, or ability of the challenge to penetrate to the lower airways. Differences between the susceptible and resistant strains in lymphocyte proliferation in vitro and delayed-type hypersensitivity in vivo after nonlethal subcutaneous infection were not demonstrated; the susceptible strain made a significantly greater antibody response to blastomyces antigens as determined by an enzyme-linked immunosorbent assay. The resistance of the C3H/HeN strain of mice, which differs from the C3H/HeJ in sensitivity to lipopolysaccharide and lacks the macrophage cytotoxicity defect of the latter, suggests that the susceptibility of C3H/HeJ mice is not related to their C3H background or the H-2 locus. As the A/HeJ strain, which also has a macrophage cytotoxicity defect, was found in this study to be the second most susceptible strain, this also suggests macrophages as the subject for further study with respect to the mechanism of genetic resistance to this infection.
The inbred mouse strains C3H/HeJ and DBA/1J have been shown to represent the extremes of susceptibility and resistance, respectively, to pulmonary blastomycosis. This pattern was completely reversed when challenge was performed by the intraperitoneal route, whether a virulent or an attenuated strain of Blastomyces dermatitidis was utilized. By a third route (subcutaneous), the differences were insignificant. Inhibition of replication of blastomyces in vitro by macrophages from both strains, before or after activation by subcutaneous infection, was similar.
A model of pulmonary blastomycosis in the mouse, in which the portal of entry is the same as natural human infection, was used to study resistance to challenge after subcutaneous infection. One week after subcutaneous infection, mice were partially resistant to pulmonary challenge, and mice challenged two weeks after infection were resistant. Measurement of cellular and humoral immune responses to Blastomyces dermatitidis antigens after subcutaneous infection showed the following. (i) Delayed-type hypersensitivity appeared 1 week after infection, and responses increased for 3 weeks thereafter. (ii) Proliferative responses in vitro appeared in spleen cells at 1 week and in contralateral lymph node cells at 3 weeks, (iii) Serum antibody, detected by an enzyme-linked immunosorbent assay, appeared 1 week after infection and then increased in titer. (iv) Peritoneal macrophages were activated to inhibit replication of B. dermatitidis in vitro by the first week after infection. Prior subcutaneous infection also resulted in rapid clearing of a second subcutaneous challenge, as well as resistance to a lethal intraperitoneal challenge. This resistance was associated with the development of cell-mediated and humoral immune responses. These data provide a chronological framework for selective transfer experiments.
A large body of experimental data has demonstrated the central role of T cells in acquired resistance to the dimorphic fungus Blastomyces dermatitidis. We examined the human T-cell response to WI-1, a 120-kDa B. dermatitidis yeast cell surface protein recently shown to be an immunodominant antigen of the B-cell response in infected humans. Peripheral blood lymphocytes from 10 blastomycosis patients studied proliferated in response to WI-1 (mean, 19,431 cpm) and to the standard, crude cell wall antigen, Blastomyces alkali- and water-soluble antigen (B-ASWS) (mean, 19,131 cpm); lymphocytes from 10 histoplasmosis patients and 10 normal control subjects did not respond to WI-1. WI-1 stimulation of patient lymphocytes and rechallenge with WI-1 or B-ASWS showed that the antigens share immunodominant epitopes. Of 100 WI-1-responsive T-cell clones derived from peripheral blood, 10 were studied in detail to assess the phenotype, function, and ligands recognized. The clones exhibit the CD3+ CD4+ phenotype of helper T cells; 2 of 10 clones (and 21% of antigen-stimulated peripheral blood lymphocytes) use the V beta 8 T-cell receptor gene element to respond to WI-1. All the clones proliferate in response to both WI-1 and B-ASWS but not other fungal antigens, and some mediate potent cytolytic effects on WI-1- and B-ASWS-labeled targets. WI-1 recognition requires antigen processing and presentation of epitopes in association with HLA-DR (to noncytolytic clones) and HLA-DP (to cytolytic clones). From these findings, we conclude that CD4+ T cells with regulatory and cytolytic properties are involved in the development of acquired resistance of B. dermatitidis, that the cells are directed against WI-1, and that the manner of display of WI-1 peptide epitopes in conjunction with major histocompatibility complex class II may influence the profile of the immune response.
Antiserum was prepared in rabbits against the A antigen and a new antigen (labeled the D antigen) of yeast-phase cells of Blastomyces dermatitidis by using immunoelectrophoretic precipitin arcs as vaccine. The antiserum can be used as a reference serum in the immunodiffusion test for identyfying antibodies to the A antigen in sera from patients thought to have blastomycosis. Antibodies to the D antigen have not yet been found in human sera. The rabbit antiserum that was absorbed with Histoplasma capsulatum yeast-phase cells did not react in the complement fixation test with either H. capsulatum yeast-phase or mycelial-phase complement fixation antigen. Therefore, it could also be used as a positive control serum in the complement fixation test. A fluorescent-antibody conjugate prepared from the absorbed serum was found to be valuable for the identification of yeast-phase cells of B. dermatitidis.
This report describes the first well-documented reported case of the recovery of Blastomyces dermatitidis from the blood of a patient with disseminated blastomycosis. The isolate was recovered by using a lysis-centrifugation method and inhibitory mold agar after 6 days of incubation at 30 degrees C. One of six blood samples collected yielded a positive culture.
We report results of an immunoassay for Blastomyces dermatitidis antigenuria. Sensitivity was 92.9%, and specificity was 79.3%. Cross-reactions occurred in 96.3% of patients with histoplasmosis, 100% of patients with paracoccidioidomycosis, 70% of patients with penicilliosis marneffei, 2.9% of patients with cryptococcosis, and 1.1% of patients with aspergillosis. Reproducibility was 96.3%. These findings support a potential role for antigen testing in blastomycosis.