Association between facial cutaneous coccidioidomycosis and meningitis.

The skin is frequently a site of extrapulmonary dissemination in patients with coccidioidomycosis. Clinical experience in an endemic area suggests an association between facial cutaneous coccidioidomycosis and meningitis. Awareness of this association is important because coccidioidal meningitis is the most ominous site of spread in coccidioidomycosis. In this study, we assess whether cutaneous dissemination involving the face is associated with meningitis to a greater degree than that limited to the body. We retrospectively reviewed the medical records of 201 patients from 1987 to 1996 with disseminated coccidioidomycosis and found 30 patients with cutaneous involvement. Their mean age was 29.5 +/- 11.6 years; 20 patients were male; 14 were African American, 12 were Hispanic, 3 were white, and 1 was Asian. Nineteen patients had facial involvement, and 11 had isolated body involvement. Meningitis developed in 11 patients, 10 with facial involvement and 1 with only body involvement. Patients with facial lesions were more likely to have meningitis (odds ratio, 11.1; 95% confidence interval, 1.1 to 529, P = .023). The identification of a subgroup of patients at significant risk of developing meningitis may allow earlier detection and perhaps improved management of patients with meningeal disease.

Vasculitic and encephalitic complications associated with Coccidioides immitis infection of the central nervous system in humans: report of 10 cases and review.

Six cases of apparent and four cases of histopathologically confirmed vasculitis of the central nervous system (CNS), including one case of histopathologically documented vasculitis with encephalitis associated with coccidioidal meningitis (CM), are presented. Vasculitic complications included changes in mental status as well as stroke-like findings of aphasia, hemianopsia, and hemiparesis. Seven patients died. Vasculitic complications were unanticipated and often abrupt in onset, and delayed therapeutic intervention was characteristic. The diagnosis of vasculitis/encephalitis due to Coccidioides immitis infection must be based on clinical judgment, since serum antibody titers, cerebrospinal fluid findings, and initial radiological studies are not always helpful. Institution of both intravenous and intracisternal administration of amphotericin B and possibly concomitant intravenous administration of dexamethasone may be warranted in situations in which the association of C. immitis with CNS vasculitis or encephalitis appears likely before serologic or cultural confirmation of C. immitis infection involving the CNS is available.

The pathology of pulmonary cryptococcal infections in the acquired immunodeficiency syndrome.

Specimens from premortem pulmonary cytology, transbronchial biopsy, and autopsy were studied in 11 patients with acquired immunodeficiency syndrome who developed pulmonary cryptococcal disease. Nine of 11 patients had culture-proved cryptococcal meningitis. Extremely low T-cell helper/suppressor ratios (mean, 0.12) were observed in seven of 11 patients. In six of eight patients, transbronchial biopsy specimens showed a characteristic interstitial pattern with yeasts in the alveolar septae, minimal cellular inflammation, and no well-formed granulomas. On cytologic examination, organisms were present in seven (100%) of seven cell blocks and five (83%) of six smears prepared from the bronchoalveolar lavage, and in five (63%) of eight bronchial brushings. Small, poorly encapsulated yeast forms were sometimes present, requiring mucicarmine and acid mucopolysaccharide stains for confirmation of the diagnosis of pulmonary cryptococcosis. Overall, bronchoscopy yielded a diagnosis in seven of eight patients. At autopsy, two of five patients demonstrated an interstitial pattern of infection in all lobes of the lung with marked pleural thickening and giant-cell formation; two other patients showed mixed interstitial and intra-alveolar cryptococcal infiltrates. Nodal and disseminated infection were present in four patients. In patients with acquired immunodeficiency syndrome who have cryptococcal meningitis, pulmonary cryptococcal disease is common and must be distinguished from other opportunistic infections.

Asbestos disease in family contacts of shipyard workers.

Radiologic signs of pulmonary asbestos disease were found in 11.3 per cent of 274 wives of shipyard workers who were 20 or more years from initial hiring-on in shipyards in Los Angeles County. Asbestosis was also found in 7.6 per cent of 79 sons and 2.1 per cent of 140 daughters of these workers. The wives, sons, and daughters were without occupational exposure. Comparable radiographic signs were not found in comparison groups. It is probable that asbestos exposure in the household places these family members at risk for mesothelioma and lung cancer.

Treatment of coccidioidomycosis with ketoconazole: an evaluation utilizing a new scoring system.

The evaluation of the response of patients with coccidioidomycosis to any therapeutic modality is a major challenge. A numerical scoring system was devised to quantitate separately the severity of disease on clinical presentation, the findings on chest film, bone scan, gallium scan, serology and skin test with coccidioidin and spherulin. The scoring system was used to evaluate the response to treatment with ketoconazole of seven patients with infiltrate pulmonary coccidioidomycosis; 20 patients with chronic cavitary coccidioidomycosis; and 40 patients with disseminated coccidioidomycosis. Dissemination included the soft tissue in 15, bone in 15, synovium in 11 and skin in 18. In all categories clinical severity scores improved dramatically. Radiographic scores showed similar improvement in cases of infiltrative pulmonary coccidioidomycosis but showed no change in cavitary coccidioidomycosis. Serology scores improved significantly (-2 or more) in one of seven infiltrative pulmonary cases, three of twenty chronic cavitary cases and twenty-three of forty disseminated cases. Among those with adequate mycology followup, cultures converted to negative in two of three infiltrative pulmonary coccidioidomycosis; seven of fourteen chronic cavitary coccidioidomycosis; and sixteen of twenty-two with disseminated disease. Unfortunately, when ketoconazole was discontinued or interrupted, symptoms recurred in four of twenty (20 percent) with chronic cavitary and ten of forty (25 percent) of disseminated cases. The disease in two patients progressed while on ketonconazole. One of those developed meningitis.

Coccidioidal pulmonary cavities with rupture.

Twenty-three patients with spontaneous rupture of a pulmonary cavity with a pyopneumothorax resulting from coccidioidomycosis are presented. Clinical and laboratory findings, medical and surgical treatment, and complications are detailed. Skin tests are not helpful in making a diagnosis. Although complement fixation titers were elevated in all patients and cultures were positive in 21, these laboratory tests should not delay surgical treatment. Surgical treatment included seven lobectomies, thirteen partial lobectomies, and one pneumonectomy. Two patients did not undergo surgical resection. Seventeen required some degree of decortication. There were three major complications and no deaths. Prompt operation is recommended when the diagnosis is suspected. Reasons for postponement include delay in seeking treatment, poorly controlled diabetes, and other complicating medical factors. The extent of surgical resection may have to be limited because of the extensive contamination of the pleural space. Amphotericin B was administered in 10 patients. The drug should be administered when the cavity ruptures in the acute phase of the disease, in all patients with diabetes, in delayed operations, in patients with concomitant medical problems, and when the extent of resection is limited to obtain immediate obliteration of the pleural space.

Ketoconazole for treatment of disseminated coccidioidomycosis.

Of 29 selected patients with disseminated coccidioidomycosis, 27 were treated for at least 6 months with ketoconazole, 200 to 600 mg/d. Two patients had progression of coccidioidal disease shortly after starting ketoconazole, and one developed meningitis. Seven of eight patients with synovitis had prompt improvement in symptoms, but four either had recurrent synovial thickening without recoverable Coccidioides immitis or could not remain free of symptoms off the drug. The response of osteomyelitis to ketoconazole was hard to assess; three of eight cases clearly improved and none progressed. Abscess or sinus formation clearly improved in eight of patients; five remained free of disease after the drug was discontinued. Skin lesions improved in six of nine; three lesions remain healed off the drug. Ketoconazole is absorbed readily after oral ingestion and has little toxicity. In the dosages used, it seems to suppress but not eradicate C. immitis. The drug may be able to stabilize the infection while cell-mediated immunity is restored.

Ketoconazole for treatment of chronic pulmonary coccidioidomycosis.

Twenty-one patients with chronic pulmonary coccidioidomycosis were treated with ketoconazole. In 16 patients with chronic cavitary disease, nine improved, four showed no change, and the condition of three deteriorated; three of nine patients had culture conversion. Roentgenograms showed improvement in two patients, no change in 12, and deterioration in two. Serologic improvement was not noted. In five patients with persistent infiltrative disease, the response was more favorable. Radiographic improvement, culture conversion, and serologic improvement were seen in most patients. Ketoconazole-induced side effects were mild and of short duration, ending in the first days of therapy. Ketoconazole seems to be of significant value in infiltrative pulmonary disease, but seems unable, at the doses used, to change finding in the sputum or to change radiographic findings in chronic cavitary disease. Further long-term observation is necessary to evaluate fully the role of this drug in chronic pulmonary coccidioidomycosis.

Dinitrochlorobenzene responsivity: difference between patients with severe pulmonary coccidioidomycosis and patients with disseminated coccidioidomycosis.

Immunologic responses in 15 patients with severe pulmonary coccidioidomycosis and in 50 patients with disseminated coccidioidomycosis were measured by determination of complement-fixing (CF) antibody titers to coccidioidin in serum, coccidioidin (1:100) skin tests, and sensitization to dinitrochlorobenzene. Among the patients with desseminated coccidioidomycosis, the nine with CF antibody titers of less than or equal to 1:8 had normal responses to dinitrochlorobenzene, but the 41 with titers of greater than or equal to 1:16 had responses that were significantly lower than those of controls (P less than 0.001). In contrast, all patients with severe pulmonary coccidioidomycosis had CF antibody titers of greater than or equal to 1:16 and had responses to dinitrochlorobenzene that were greater (but not significantly greater) than those of controls. Among subjected with antibody titers of greater than or equal to 1:16, responsiveness to coccidioidin was found in 27% of those with severe pulmonary disease and in 39% of those with disseminated disease. Thus impaired responsivity to dinitrochlorobenzene in coccidioidomycosis is restricted to patients who have disseminated illness and high titers of CF antibody and is separable from lack of responsiveness to coccidioidin.

Tempest from Tehachapi takes toll or Coccidioides conveyed aloft and afar.

New cases of acute primary coccidioidomycosis in large numbers resulted from a windstorm that blew through Kern County, California, on December 20, 1977. In most of these cases clinically apparent infections developed in early and mid-January 1978 and occurred not only in persons exposed directly to the dust raised by the windstorm but also among those in many areas to the north and west of Kern County. The exposure to the dustborne Coccidioides immitis was brief because of the arrival of drenching rains, but the continued heavy rainfall increased the potential for large numbers of cases of coccidioidomycosis to occur in the summer-fall season.

Pulmonary mycetoma due to Coccidioides immitis.

Pulmonary mycetoma due to Coccidioides immitis has been reported on three occasions. The present case is the fourth such report occurring in a patient with widely disseminated disease. Spherules and hyphae were found in the specimen. While the active pulmonary and extra-pulmonary lesions responded well to therapy with amphotericin B, resection was required to eliminate the residual mycetoma and its attendant hemoptysis.

Acute coccidioidal pleural effusion.

Acute coccidioidal pleural effusions were studied in 28 patients. Coccidioidal pleural effusion appeared to be secondary to direct spread of contigous parenchymal infection, rather than to hematogenous dissemination, in more than 90 per cent of these patients. Only 2 of 28 patients had the concomitant development of disseminated infection, and both patients possessed factors known to predispose to dissemination. Because of the excellent prognosis in most patients, therapy in patients with coccidioidal pleural effusion should be expectant. This is true even when substantial increases occur in complement fixation titers; such elevations were frequent in this series. Cultures of pleural biopsy specimens were the most rewarding cultural source in this series, being positive in all 8 patients in whom such biopsy specimens were cultured. Dermal hypersensitivity, including erythema nodosum and erythema multiforme, was commin in patients whose clinical course was uncomplicated.

Dinitrochlorobenzene responsivity in disseminated coccidioidomycosis: an inverse correlation with complement-fixing antibody titers.

The immunologic status of 25 patients with disseminated coccidiodomycosis was evaluated by serum anticoccidioidin complement-fixing antibody levels, coccidiodin skin tests, and dinitrochlorobenzene (DNCB) sensitization. In the 10 patients who had disseminated disease and a complement-fixing titer of 1:32 or less, responses to DNCB were similar to those of 20 controls. In the 15 patients with disseminated disease and a complement-fixing titer of 1:64 or more, responses to DNCB were statistically significantly diminished compared to controls (p = 0.002). Since the complement-fixing titer is associated with extent of dissemination, these results signify a relationship between diminished DNCB responses and extensive dissemination. Of the several hypotheses which might explain this relationship, we find the most attractive is that of a nonspecific deficiency of cell-mediated immunity developing secondarily to extensive disseminated disease.