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Disseminated coccidioidomycosis associated with extreme eosinophilia.

Primary coccidioidomycosis is frequently accompanied by eosinophilia in the range of 5%-10% of the peripheral white blood cell count. Dissemination of Coccidioides immitis to organs such as skin, bone, joints, and CNS usually is associated with risk factors such as sex (male), race (non-Caucasian), pregnancy, and immunosuppression. We report a case of coccidioidomycosis in an otherwise healthy African-American man with 72% eosinophilia who had dissemination to the skin, and we review cases in the literature of disseminated disease associated with eosinophilia. Marked eosinophilia may be an important early clue that dissemination of coccidioidomycosis has occurred.

Adult↗

Diabetic ketoacidosis associated with pulmonary coccidioidomycosis.

We describe three patients who developed diabetic ketoacidosis in association with pulmonary coccidioidomycosis and review the literature concerning the influence of diabetes on coccidioidomycosis. Our cases demonstrate that coccidioidomycosis is an infection that can be associated with diabetic ketoacidosis and that should be considered in the differential diagnosis of pneumonia in patients who live in a region in which Coccidioides immitis is endemic.

Adult↗

Coccidioidomycosis in liver transplant patients.

Eight (0.59%) of 1,347 patients who underwent liver transplantation at the UCLA Medical Center (Los Angeles) developed coccidioidomycosis. Whereas only one case occurred during the first 8 years and 10 months of the UCLA Liver Transplant Program (February 1984 to December 1992), seven cases occurred within the following 23-month period (December 1992 to November 1994). The median time of onset for infection after transplantation was 8 weeks (range, 4-312 weeks). Clinical presentations of patients with coccidioidomycosis included pneumonia (six cases), pneumonia with meningitis (one case), hepatitis (one case), and monoarticular arthritis (one case). Despite therapy with amphotericin B alone (six cases) or amphotericin B plus fluconazole (two cases), infection was fatal in four of eight cases. As of this writing, the four surviving patients are receiving chronic maintenance therapy with either fluconazole (three patients) or itraconazole (one patient). These experiences show that coccidioidomycosis can be a serious and frequently fatal infection after liver transplantation and that the incidence of this disease appears to be increasing.

Adult↗

Detection of serum antibodies in coccidioidomycosis by solid-phase radioimmunoassay.

A radioimmunoassay (RIA) was developed to measure antibody in coccidioidomycosis with improved quantitation. Sera from 41 patients with active coccidioidomycosis had a mean +/- SD value of 0.6 +/- 0.49 mg/ml. Twelve healthy controls and 23 patients with noncoccidioidal diseases had a mean level of 0.06 +/- 0.12. Complement fixation (CF) and RIA titers were also compared with the clinical course in 19 patients with active coccidioidomycosis (seven had pulmonary disease; 12 had disseminated disease). The RIA was most useful in pulmonary cases. Pulmonary patients who experienced an improvement in symptoms more often experienced a drop in RIA titer (all of four patients) than CF titer (two of four). Similarly, pulmonary patients who demonstrated radiographic improvements experienced a drop in RIA titer (four of five) more often than a drop in CF titer (three of five). In patients with disseminated disease, there was agreement between the two assays and the clinical symptom score.

Antibodies, Fungal↗

Coccidioidomycosis among visitors to a Coccidioides immitis-endemic area: an outbreak in a military reserve unit.

An outbreak of coccidioidomycosis occurred in a US Marine reserve unit based in Tennessee after a 3-week training exercise in California that involved substantial exposure to soil and dust. Interviews and serologic testing were done on three occasions (6, 11, and 15 weeks) after the men returned from California, and spherulin skin tests were done at 6 months. Of 27 men, 8 (30%) had evidence of recent coccidioidal infection. Of these, 7 (88%) had an illness consistent with coccidioidomycosis that, despite medical evaluation, was diagnosed incorrectly in 5 men (71%). Diagnosis of coccidioidal pneumonia outside an area in which Coccidioides immitis is endemic is unlikely unless the health care provider is aware that the patient traveled recently. Detection of coccidioidomycosis could be facilitated if organizations that regularly send people to C. immitis-endemic regions were to inform these persons about the risks of infection.

Adult↗

Detection of coccidioidal antibodies by 33-kDa spherule antigen, Coccidioides EIA, and standard serologic tests in sera from patients evaluated for coccidioidomycosis.

During a 9-month study of patients being evaluated for coccidioidomycosis, 1 or more serum samples were obtained from 138 patients with an illness suggestive of recent infection. In this group, standard immunodiffusion tests of unconcentrated sera were positive for 25; 49 additional patients had at least 1 reactive test result by newer enzyme-linked serologic tests. At least 11 of these 49 patients had coccidioidomycosis as determined by culture or subsequent standard serologic tests. Patients with coccidioidomycosis identified only by newer tests had fewer or milder clinical abnormalities than did patients in whom the disease was detected by standard tests. For 31 other patients with illness of a chronic or undetermined duration, newer tests detected only 10 more than the 18 identified by standard tests, suggesting that later in the course of illness, standard testing gains in sensitivity for coccidioidal infection.

Antibodies, Fungal↗

Cytokine production by peripheral blood mononuclear cells in human coccidioidomycosis.

The production and mRNA expression of the cytokines interferon-gamma (IFN-gamma) and interleukin (IL)-4, -10, and -12 by peripheral blood mononuclear cells (PBMC) after incubation with the coccidioidal antigen toluene spherule lysate (TSL) from various subjects were measured. The IFN-gamma concentration in PBMC supernatants incubated for 72 h from 8 subjects with disseminated coccidioidomycosis was significantly less than that from 7 healthy, coccidioidal-immune subjects (P = .015). No differences were seen among the subject groups in the concentrations of IL-4, -10, or -12. By use of competitive polymerase chain reaction, PBMC from subjects with disseminated coccidioidomycosis also expressed less mRNA for IFN-gamma and IL-12 than did cells from healthy, immune subjects. These data suggest that patients with disseminated coccidioidomycosis have a diminished T helper lymphocyte type 1 response.

Base Sequence↗

Disseminated coccidioidomycosis in an immunocompetent person living in New York City.

Coccidioidomycosis is a disease caused by Coccidioides immitis, a soil-inhabiting fungus endemic to the desert climate of the southwestern United States and Central and South America. We report a case of disseminated coccidioidomycosis in a previously healthy person living in New York City, who was initially thought to have tuberculosis. The incidence of coccidioidomycosis has been increasing in both endemic and nonendemic areas, but diagnosis is often delayed or missed in nonendemic areas, resulting in extensive and unnecessary medical workup for other diseases or progression to serious disease. Therefore, clinicians should increase their awareness and consideration of this disease in patients with chronic systemic illness.

Adult↗

Total ionized serum calcium and parathyroid hormone levels in patients with disseminated coccidioidomycosis.

Twenty-one patients with severe coccidioidomycosis, including eight with osseous lesions, were admitted to the University of California, Davis, Medical Center, during a recent epidemic. Transient mild ionized hypercalcemia occurred in only two patients, and a tendency toward low normal ionized calciums was noted. Parathyroid hormone levels appeared to be appropriate for the ionized calcium in these patients. There were no significant differences in ionized calcium levels of parathyroid hormone levels among patients with and without osseous coccidioidomycosis. We conclude that hypercalcemia is rare in coccidioidomycosis, even with extensive bony involvement.

Calcium↗

Septic shock in coccidioidomycosis.

OBJECTIVES: To describe the clinical and laboratory parameters of patients with septic shock following infection with Coccidioides immitis, estimate the incidence of septic shock from coccidioidomycosis, and outline clues that may be helpful in early diagnosis of this syndrome. DESIGN: Retrospective, descriptive case series. SETTING: A 250-bed general public hospital in Kern County, CA. PATIENTS: Eight patients diagnosed with septic shock from infection with C. immitis from September 1991 to December 1993. Five were Hispanic, two were Filipino, and one was African-American. The diagnosis of C. immitis was made by microscopic examination and culture of the organism from sputum or other sites. Septic shock was diagnosed using criteria formulated by the American College of Chest Physicians Consensus Conference/Society of Critical Care Medicine. MEASUREMENTS AND MAIN RESULTS: No patient had traditional immunocompromising conditions. All patients had pulmonary symptoms and were symptomatic for a mean duration of 19.4 +/- 19.8 days before admission. One patient presented with septic shock and the remaining seven developed shock during their hospital course. Serology for coccidioidomycosis was positive in six patients. The mean cardiac index was 5.8 +/- 1.9 (SD) L/min/m2, the mean arterial pressure was 71.0 +/- 16.7 mm Hg, the mean pulmonary artery occlusion pressure was 16.9 +/- 3.5 mm Hg, and the mean systemic volume resistance index was 846.6 +/- 224.1 dyne-sec/cm5xm2. All patients developed acute respiratory distress syndrome. Coccidioidomycosis was recognized or considered in only five of eight patients before they developed septic shock. Despite therapy with amphotericin B, all patients died. One patient died of progressive pulmonary disease, two patients suffered an acute arrest, and five patients developed progressive multiple organ system failure and died with additional organ involvement. CONCLUSIONS: Septic shock following infection with C. immitis is an ominous yet underrecognized condition. Hemodynamic parameters and cytokine concentrations were not significantly different from values seen in gram-negative septic shock. Clinical clues to the diagnosis include duration of illness and conspicuous pulmonary involvement. Patient outcome in this series was poor but may improve with increased recognition of septic shock in infections from C. immitis.

Adult↗

Coccidioidomycosis during human immunodeficiency virus infection. A review of 77 patients.

Through a retrospective review, we identified 77 previously unreported cases of coccidioidomycosis during HIV infection. Patients were classified into 1 of 6 categories based on their primary clinical presentation: 20 had focal pulmonary disease (Group 1), 31 had diffuse pulmonary disease (Group 2), 4 had cutaneous coccidioidomycosis (Group 3), 9 had meningitis (Group 4), 7 had extrathoracic lymph node or liver involvement (Group 5), and 6 has positive coccidioidal serology without a clinical focus of infection (Group 6). Coccidioidal serologies were positive on initial testing in 83% of the patients in whom such serologic testing was performed. Sera from 39% of patients were positive for TP antibodies while 74% had CF antibodies. Eleven of 12 seronegative patients had pulmonary disease (Group 1 or 2). Serologic results of other patients sent to a single reference laboratory were similar, with 26% positive for immunodiffusion TP antibodies and 79% positive for immunodiffusion CF antibodies. For the 77 patients in this study, the CD4-lymphocyte count was below 0.250 X 10(9) cells/L in 46 of the 55 patients who had this test performed, and a low CD4 count was significantly associated with mortality (p less than 0.01). At the time of follow-up, 32 of the 77 patients (42%) had died. There were significantly more deaths in those with diffuse pulmonary disease (Group 2) than in other groups (p less than 0.001). Amphotericin B, ketoconazole, fluconazole, and itraconazole were all used as antifungal therapies. Outcome could not be related to the therapy used. Of note, 3 patients developed coccidioidomycosis while receiving ketoconazole for other conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Coccidioidomycosis of the eyelid.

A 77-year-old woman presented with an ulcerated nodule on her right lower eyelid that was unresponsive to broad-spectrum antibiotics or incision and drainage. Coccidioidomycosis was suspected because of previous serologic testing and concurrent indurated cutaneous nodules. Although skin biopsies were not diagnostic, cultures from the eyelid were positive for Coccidioides immitis. The patient was initially treated with oral fluconazole, with resolution of the eyelid and skin lesions. She ultimately completed a 6-month course of oral azole therapy, and at 18-month follow-up she was symptom free. Few cases of granulomatous coccidioidomycosis of the eyelids have been reported. The clinical features of this infection are not specific, and the diagnosis is often difficult. Presentation can mimic bacterial infection or malignant neoplasm, leading to delayed or inappropriate treatment. We describe an unusual ulcerative lesion of the eyelid that led to a diagnosis of disseminated coccidioidomycosis.

Aged↗

Coccidioidomycosis causing massive cervical lymphadenopathy.

Coccidioidomycosis involving the head and neck is uncommon. We present a case of a patient with disseminated coccidioidomycosis and massive submandibular cystic lymphadenopathy unresponsive to systemic antifungal treatment. It is our impression that significant clinical improvement resulted from concomitant needle aspiration of the cystic nodes to decrease fungal load and modification of systemic medication. Although reduction of fungal burden may provide an improved response to antifungal therapy, disseminated coccidioidomycosis is a systemic disease that requires appropriate systemic therapy.

Child, Preschool↗

Coccidioidomycosis of the prostate gland: two cases and a review of the literature.

Coccidioidomycosis prostatitis is an uncommon presentation of disseminated coccidioidomycosis, a fungal disease endemic in the southwestern United States. Coccidioidomycosis prostatitis should be considered in the differential diagnosis of a patient from an endemic region with evidence of persistent sterile pyuria, prostatitis, or granulomatous disease of the prostate. Diagnosis is established by biopsy, and treatment includes either an azole or amphotericin B. We present the twelfth and thirteenth reported cases and provide a review of the literature.

Aged↗

Posaconazole therapy for systemic coccidioidomycosis in a chimpanzee (Pan troglodytes): a case report.

Systemic coccidioidomycosis was diagnosed in a 4-year-old male chimpanzee (Pan troglodytes) with ascites and failure to thrive. Physical examination, laboratory and radiological studies, and exploratory laparotomy showed signs of systemic fungal infection that included penetration into the central nervous system (CNS). Serum and cerebrospinal fluid (CSF) titres, along with ascites cytology findings, confirmed the presence of Coccidioides immitis. However, the organism could not be cultured from the CSF. Treatment with fluconazole 10 mg kg(-1) daily for 6 months was not associated with clinical improvement. Subsequent treatment with posaconazole 50 mg kg(-1) daily for approximately 24 months resulted in negative serum titres and improved clinical status. Illness not directly related to the C. immitis infection caused the chimpanzee's deterioration and eventual killing. Histological examination performed during necropsy provided no evidence of coccidioidomycosis; however, a positive C. immitis serum antibody titre was noted. The successful suppression of coccidioidomycosis observed in this chimpanzee suggests that posaconazole may have a role in the treatment of CNS infections caused by susceptible fungi.

Animals↗

Therapeutic effect of the triazole Bay R 3783 in mouse models of coccidioidomycosis, blastomycosis, and histoplasmosis.

A new triazole, Bay R 3783, was compared with ketoconazole, itraconazole, and fluconazole, which were given via the alimentary tract at three dosages, and amphotericin B, which was given at 1 mg/kg intraperitoneally, in murine models of the systemic mycoses coccidioidomycosis, histoplasmosis, and blastomycosis. In a pulmonary coccidioidomycosis model, Bay R 3783, fluconazole, and itraconazole were essentially equally efficacious and more active than ketoconazole in protecting mice against death; but they were inferior to amphotericin B. In a short-term organ load experiment, Bay R 3783 and amphotericin B were equally effective and were more effective than the other drugs in reducing the amount of Coccidioides immitis in the lungs. Against meningocerebral coccidioidomycosis, Bay R 3783, itraconazole, and fluconazole at 25 mg/kg and amphotericin B prevented death only during therapy, with mortalities ensuing shortly thereafter. In mice with systemic histoplasmosis, Bay R 3783 and itraconazole at 25 mg/kg and amphotericin B prevented death in all mice through a 44-day observation period. Clearance of Histoplasma capsulatum from organs was similar in mice treated with Bay R 3783 and itraconazole; this clearance was greater than that in mice treated with ketoconazole and fluconazole but less than that in mice treated with amphotericin B. In mice with systemic blastomycosis, Bay R 3783 at 25 mg/kg yielded 90% survivors at 60 days, which was greater than that achieved with amphotericin B (60%) or itraconazole (30%). Clearance of Blastomyces dermatitidis from the lungs was greatest with Bay R 3783, followed by that with amphotericin B, itraconazole, fluconazole, and ketoconazole, in that order. Therefore, Bay R 3783 showed effectiveness comparable to or exceeding those of itraconazole and fluconazole and exceeding that of ketoconazole against these systemic mycoses in mice.

Animals↗

Serology of coccidioidomycosis.

Serologic tests have assisted in the diagnosis and prognosis of coccidioidomycosis for a half-century. The causative agent, Coccidioides immitis, is a dimorphic fungus existing in a hyphal form with arthroconidia in nature and in the usual culture. The arthroconidia represent the inhaled infective forms which in vivo and under special laboratory conditions form spherules which endosporulate. The culture filtrate/autolysate (coccidioidin) from the hyphal phase has provided antigens of suitable reliability for currently used serologic tests. These tests are primarily to determine the two major antibody responses: the early immunoglobulin M (IgM) response is useful in the diagnosis of acute primary coccidioidomycosis. Later, IgG is produced and usually outlasts the IgM, persisting in chronic coccidioidomycosis. The IgM is detectable by tube precipitin, a corresponding immunodiffusion, or latex particle agglutination tests. The pertinent antigen(s) is heat stable and pronase resistant and appears to be largely carbohydrate, mainly mannose with some 3-O-methyl mannose. The IgG detectable in the serum and other body fluids by complement fixation and a corresponding immuno-diffusion is useful in diagnosis, and its quantitation provides an indicator of progression of disease (increasing titer) or regression (decreasing titer). The pertinent antigen appears to be a heat-labile, pronase-sensitive protein which in an unreduced form has a molecular weight of 110,000. A third very useful serologic procedure is the exoantigen test for identification of putative cultures of C. immitis.

Animals↗

Coccidioidomycosis osteomyelitis masquerading as a bone tumor. A report of 2 cases.

BACKGROUND: Coccidioidomycosis involving the lung is common in endemic areas. However, it is unusual for it to present as a solitary bone lesion. CASES: Two cases of Coccidioides immitis osteomyelitis clinically and radiographically mimicked a primary bone tumor. Fine needle aspiration (FNA) biopsy of these lytic bone lesions yielded diagnostic material. Aspirated material in 1 case showed a suppurative, granulomatous inflammation and scattered spherules with refractile walls, some containing endospores consistent with coccidioidomycosis. Smears in the other case showed acute inflammation and necrosis, and rare spherules were identified with the Gomori-mathenamine-silver stain. C immitis infection was confirmed by culture in both cases. CONCLUSION: Although rare, coccidioidomycosis can involve the bone and mimic a primary bone tumor. FNA biopsy is helpful in differentiating between inflammatory and neoplastic processes involving bone by acquiring material for cytologic studies and cultures.

Adult↗