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PubMed1993

[Pulmonary coccidioidomycosis].

Coccidioidomycosis is an acute, generally mild, respiratory disease that rarely becomes chronic or disseminated and fatal. The aetiologic agent is Coccidioides immitis, a dimorphic fungus growing in soil. The fungus is endemic in hot semi-arid areas in the USA and South America. Human beings and animals become infected by inhaling dust with arthroconidia. The fungus gives rise to either a purulent or a granulomatous inflammation or both. Clinically and radiologically, it can be confused with neoplasms and tuberculosis. The disease may be fatal in immuno-deprived persons who are also at risk of reactivation of a latent infection. Coccidioidomycosis can be detected serologically. The standard treatment of severe illness is Amphotericin B. The authors present the first histologically and serologically verified case of pulmonary coccidioidomycosis in Denmark. An increased number of coccidioidomycosis can be expected with increased travelling and an increased number of immuno-deprived persons.

Coccidioidomycosis↗

PubMed1993

Coccidioidomycosis: a persistent threat to deployed populations.

The world-wide deployability of aircrew members exposes them to a peculiar array of medical problems. Non-immune populations, upon deployment to endemic areas, may present to the deployed flight surgeon with acute, poorly recognizable syndromes, such as acute coccidioidomycosis. Alternatively, the acquisition of the chronic progressive form of coccidioidomycosis in endemic areas may be a problem for the flight surgeon, who may be faced with a poorly recognizable syndrome which first manifests itself weeks to months after the crewmember's return from deployment. We describe three cases of coccidioidomycosis in service members that highlight the difficulty in the diagnosis of this disease. These cases prompted an epidemiologic survey of recent cases of coccidioidomycosis among Air Force beneficiaries, presented here, to better define the impact of this disease on personnel assigned to endemic areas. A brief discussion of the epidemiologic and clinical features of the disease and of the aeromedical disposition of the aviator is presented.

Adult↗

PubMed1993

Coccidioidomycosis--United States, 1991-1992.

During 1991, reported cases of coccidioidomycosis (i.e., valley fever) in California increased more than three-fold over the annual number of cases reported since 1986; during 1992, the number of reported cases increased 10-fold. Coccidioidomycosis, a fungal disease caused by Coccidioides immitis, is endemic in certain parts of Arizona, California, Nevada, New Mexico, Texas, and Utah. Sporadic cases occur each year in parts of the United States in which the disease is not endemic and may present diagnostic difficulties and laboratory hazards because health-care workers may be unfamiliar with coccidioidomycosis. Recent increases in California and reports of isolated cases in areas without endemic disease suggest that physicians and laboratory personnel should be alert to the possible role of C. immitis. This report summarizes the occurrence of coccidioidomycosis in California during 1991 and 1992 and highlights three cases that occurred in areas in which the disease is not endemic.

Adolescent↗

PubMed1996

Coccidioidomycosis--Arizona, 1990-1995.

Coccidioidomycosis is a systemic infection caused by the inhalation of airborne arthroconidia from Coccidioides immitis, a soil-dwelling fungus found in the southwestern United States, parts of Mexico, and Central and South America. Clinical manifestations occur in approximately 40% of infected persons and may include mild influenza-like illness; severe pneumonia; and rarely, disseminated disease and death. During 1990-1995, the number of reported cases of coccidioidomycosis in Arizona increased by 144%. To characterize trends in and the impact of coccidioidomycosis in Arizona, the Arizona Department of Health Services (ADHS) analyzed surveillance, death-certificate, and hospital discharge data. This report summarizes the findings, which indicate that, during 1990-1995, coccidioidomycosis in Arizona disproportionately affected persons aged > or = 65 years and persons with human immunodeficiency virus (HIV) infection.

AIDS-Related Opportunistic Infections↗

PubMed1998

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.

Adult↗

PubMed2025

Type-2 immune skewing in patients with disseminated coccidioidomycosis.

BACKGROUND: Disseminated coccidioidomycosis (DCM) is an often fatal and otherwise intractable condition requiring lifelong antifungal treatment. We have previously shown that a deranged polarization of CD4+ T cells toward a Type-2 phenotype can exist in the context of DCM. Here we studied a large population of subjects to determine the frequency of abnormal Type-2 skewing of CD4+ T cells in patients with coccidioidomycosis and to identify underlying genetic mechanisms supporting this skew. METHODS: We collected peripheral blood mononuclear cells from 204 patients with coccidioidomycosis, including 96 patients with disseminated disease. We measured immune phenotypes and cytokine production by CD4+ T cells from patients and healthy controls, and comparisons between groups were made based on disease severity and demographics. Whole genome sequencing was conducted on 149 individuals who also had cytokine profiling. RESULTS: We found that ~20% of DCM patients had a CD4+ T-cell compartment that was abnormally skewed toward a Type-2 (IFN-γ-IL-4+) phenotype. Type-2 skewing was highly correlated with male sex, with 80% of moderately skewed (Th2:Th1 ratio > 1.5) and 100% of severely skewed (Th2:Th1 ratio > 2) patients being male. Co-culture of T cells with the IL4R/IL13R-blocking antibody dupilumab rectified their Th1/Th2 skewing. Sequencing revealed rare variants in genes involved in the IL-12-IFN-γ axis in several Type-2 skewed patients, and we validated one such variant in IFNGR1 as hypomorphic. CONCLUSION: Patients with DCM, especially those who are male, should be screened for Type-2 skewing of CD4+ T cells. Patients with Type-2 skewing should be additionally screened for genetic defects in the IL-12-IFN-γ axis. Our findings give a mechanistic rationale for exploring blockade of IL4R as a treatment option in Type-2 skewed patients with refractory coccidioidomycosis.

Journal Article↗

PubMed1953

Primary cutaneous coccidioidomycosis; the criteria for diagnosis and a report of a case.

Study was made of a case of coccidioidomycosis known to have resulted from primary inoculation of the organisms into the skin. Clinical observations and laboratory data were obtained at the time of clinical illness and for a period of five years thereafter. From the information thus obtained and correlation of it with what already was known of coccidioidomycosis, it was concluded that the disease originates very rarely as the result of primary cutaneous inoculation. In most instances lesions suspected to be of this type have actually resulted by dissemination of the organisms to the skin from a previously unrecognized pulmonary focus. Primary cutaneous coccidioidomycotic lesions closely resemble the primary cutaneous lesions (chancres) in other infectious granulomata, such as syphilis, tuberculosis and sporotrichosis. Spontaneous involution should occur within three months and then there should be immunity to reinfection in all but one or two per thousand instances. From these observations certain criteria were evolved by which to determine in a case of coccidioidomycosis with cutaneous manifestations whether or not the infecting organism entered through the skin.

Administration, Cutaneous↗

PubMed2005

Sweet syndrome (acute febrile neutrophilic dermatosis) associated with pulmonary coccidioidomycosis.

BACKGROUND: Sweet syndrome (acute febrile neutrophilic dermatosis) may arise in association with a variety of underlying systemic diseases. Only 1 case of coccidioidomycosis-associated Sweet syndrome has previously been reported. OBSERVATIONS: We describe 2 patients who developed Sweet syndrome during the onset of acute pulmonary coccidioidomycosis. Systemic antifungal therapy was given in both cases. Respiratory symptoms and skin lesions resolved within 5 weeks. CONCLUSIONS: Sweet syndrome may be a presenting feature of coccidioidomycosis. Recognition of the underlying pulmonary infection is important so that inappropriate treatment with systemic corticosteroids can be avoided.

Administration, Oral↗

PubMed2006

The exanthem of acute pulmonary coccidioidomycosis: Clinical and histopathologic features of 3 cases and review of the literature.

BACKGROUND: Coccidioidomycosis may be associated with a reactive generalized cutaneous eruption early in the course of the illness. Detailed descriptions in the literature are scarce. OBSERVATIONS: We describe 3 patients with a florid eruption associated with pulmonary coccidioidomycosis. The exanthem mimicked erythema multiforme clinically but not histologically. In 2 of the patients, the eruption began before the presence of detectable antibodies in the serum. CONCLUSION: The presence of the exanthem, in combination with fever and/or pneumonia, was a helpful clue to the diagnosis of coccidioidomycosis.

Acute Disease↗

PubMed1991

Laryngeal involvement in disseminated coccidioidomycosis.

Coccidioidomycosis is a pulmonary fungal infection endemic to the desert southwest of the United States and northern Mexico. Rarely (0.5% of cases), the fungus disseminates widely, causing life-threatening complications. Seven percent of these cases will involve the head and neck. We report a case of disseminated coccidioidomycosis that involved the larynx and cervical lymph nodes in a 40-year-old white woman who presented with hoarseness and unsuspected airway compromise. Review of the 12 reported cases of laryngeal coccidioidomycosis showed a predominance of male and dark-skinned patients; seven were children, and nine presented with airway compromise. Other reported sites of head and neck involvement include the skin, mucosa, bones of the skull, and meninges, and there have been reports of abscesses of the soft tissues and fascial spaces of the neck.

Adult↗

PubMed1998

Coccidioidomycosis of the knee diagnosed by fine-needle aspiration: a case report.

A case of septic arthritis from coccidioidomycosis in a 62-year-old man is described. The diagnosis was made by fine-needle aspiration and supported by positive cultures and exoantigen testing. Coccidioidomycosis can infect bones and joints, especially the knee. This case is presented to increase awareness of involvement of the knee by this organism, and to demonstrate the feasibility of diagnosis by fine-needle aspiration. The cytologic findings of coccidioidomycosis of the knee are described and discussed.

Biopsy, Needle↗

PubMed1996

Skeletal coccidioidomycosis: imaging findings in 19 patients.

OBJECTIVE: The objective of this study was to describe the distribution and radiologic appearance of skeletal coccidioidomycosis in 19 documented cases. DESIGN AND PATIENTS: Medical records of 19 patients (17 men, 2 women; age range 17-62 years, mean age 34 years) with clinically confirmed skeletal coccidioidomycosis were retrospectively reviewed. The patients were studied with plain radiography (n = 19), skeletal scintigraphy (n = 6), computed tomography (CT) (n = 5), and magnetic resonance imaging (MRI) (n = 1). RESULTS: Multiple lesions were seen in 11 of 19 patients (58%). Of a total of 46 lesions, 27 (59%) were described as punched-out lytic, 10 (22%) as permeative/destructive, and 9 (17%) as involving a joint and/or disk space. Lesions were identified in almost every bone (with the exception of the facial bones, ulna, carpus, and fibula) and were most commonly found in the axial skeleton (20 of 46; 43%). CONCLUSION: Skeletal coccidioidomycosis is frequently multicentric and may involve almost any bone. The axial skeleton is the most common site of involvement. Lesions are usually well demarcated but may present with an ill-defined border and permeative type of bone destruction, especially in the spine. Joint involvement is not uncommon. Plain radiographs are effective in the initial evaluation of bones and joints, scintigraphic studies can identify disseminated disease, and CT and MRI are effective in determining soft tissue involvement and spinal abnormalities.

Adolescent↗

PubMed1987

Coccidioidomycosis in adolescents presenting as chest pain.

Chest pain is a relatively common complaint in adolescents and is most often attributed to anxiety or musculoskeletal conditions. Pleuritic chest pain in association with fever and cough are frequently reported in adults with primary pulmonary coccidioidomycosis. We describe three cases in which chest pain mimicking costochondritis was the predominant initial presenting symptom of pulmonary coccidioidomycosis. In addition, in each case, recent tuberculin skin test reactivity complicated the diagnostic assessment and treatment. We conclude that, in endemic areas, coccidioidomycosis should be considered in the differential diagnosis of acute chest pain in teenagers as well as in adults.

Adolescent↗

PubMed2006

Coccidioidomycosis.

The difficulties in managing this potentially horrific disease, with its myriad manifestations, are immense, because host factors dramatically impact outcome. Coccidioidomycosis should warrant great respect among clinicians, because, even with dramatic improvements in therapies, outcomes remain poor. Although there have been outstanding successes with these new therapies, tragic losses after years of immense patient suffering still occur. Coccidioidomycosis is a geographically restricted fungus but is one that inflicts tremendous suffering on affected patients. In addition, because of travel and the influx of susceptible hosts, dramatic increases in patients at risk for infection are seen throughout the southwest United States. The extended-spectrum azoles, such as posaconazole and voriconazole, may prove to be more efficacious in the treatment of coccidioidomycosis than prior agents, including amphotericin B, fluconazole, and itraconazole. Additional resources are needed to conduct randomised, controlled clinical trials for the treatment of this disease.

Antifungal Agents↗

PubMed2005

Coccidioidomycosis of the prostate: a determination of incidence, report of 4 cases, and treatment recommendations.

OBJECTIVE: To describe the incidence of Coccidioides immitis infection of the prostate gland in an endemic area, to describe four new cases discovered, and to propose treatment recommendations for this diagnosis. METHODS: The pathology reports of all prostate tissue specimens collected at the Arizona Health Sciences Center from February 1, 1994 through January 1, 2000 and the Southern Arizona Veterans' Affairs Health Care System from January 1, 1990 through January 1, 2000 were reviewed. RESULTS: A total of 3676 pathology reports were reviewed. Forty-four cases of granulomatous prostatitis were identified (incidence=1.2%). Among these, four cases of C. immitis prostatitis were identified (incidence of granulomatous prostatitis=10%; overall incidence=0.1%). Two cases were found at radical retropubic prostatectomy and two were found on prostate needle biopsy. Five months post-radical prostatectomy one man developed symptomatic coccidioidomycosis and died of complications despite treatment with amphotericin B. Another patient who underwent a radical retropubic prostatectomy was treated with oral fluconazole for 14 months immediately after surgery and had a good response. The remaining two patients received no anti-fungal therapy and are being observed. CONCLUSIONS: Coccidioidomycosis of the prostate is rare. However, when identified, the finding should not be ignored. Patients with symptomatic coccidioidomycosis require immediate anti-fungal therapy. When the diagnosis is an incidental finding and the patient does not manifest symptoms, the degree of tissue violation involved in making the diagnosis influences the need for treatment. Patients with minimal tissue violation (i.e. needle biopsy) can be observed whereas patients with more extensive tissue violation (i.e. prostatectomy) should receive anti-fungal therapy.

Aged↗

PubMed1995

Fluconazole in the treatment of chronic pulmonary and nonmeningeal disseminated coccidioidomycosis. NIAID Mycoses Study Group.

PURPOSE: To determine the efficacy and safety of fluconazole as treatment for coccidioidomycosis. PATIENTS AND METHODS: This was a multicenter, open-label, single-arm study. Of 78 patients enrolled, 22 had soft-tissue, 42 had chronic pulmonary, and 14 had skeletal coccidioidomycosis. Forty-nine had at least one concomitant disease, 7 of whom had HIV infection. Patients were given oral fluconazole 200 mg/d. Nonresponders were increased to 400 mg/d. Treatment courses were long: a mean of 323 +/- 230 days at 200 mg and 433 +/- 178 days at 400 mg. Predefined assessment of disease-related abnormalities was performed at the time of enrollment and repeated at least every 4 months. A satisfactory response was defined as any reduction of baseline abnormality by month 4 and at least 51% reduction by month 8. RESULTS: Among 75 evaluable patients, a satisfactory response was observed in 12 (86%) of the 14 patients with skeletal, 22 (55%) of the 40 patients with chronic pulmonary, and 16 (76%) of the 21 patients with soft-tissue disease. Five patients (7%) required modification of treatment due to toxicity. Forty-one patients who responded were followed off drug. Fifteen (37%) of them experienced reactivation of infection. CONCLUSION: Fluconazole 200 or 400 mg/d is well tolerated and a moderately effective treatment for chronic pulmonary or nonmeningeal disseminated coccidioidomycosis. The relapse rate following therapy is high. Treatment trials with higher doses appear warranted. The relative efficacy of fluconazole versus other azoles or amphotericin B remains unknown.

Adult↗

PubMed2003

In vitro modulation of cytokine production by lymphocytes in human coccidioidomycosis.

The modulation of the cytokine response to coccidioidal antigen by lymphocytes from donors with coccidioidomycosis was examined. In initial experiments, samples from 13 healthy immune donors and seven donors with active coccidioidomycosis anergic to the coccidioidal antigen T27K were assessed for CD3 lymphocyte expression of intracellular IFN-gamma using whole blood analysis. Addition of 10 ng/ml of recombinant IL-12 significantly increased response to T27K among immune and anergic subjects (p<0.05), but the percent of cells expressing IFN-gamma was still significantly greater for immune subjects. Among immune donors, the percentage of CD3 lymphocytes expressing IFN-gamma was significantly reduced with the addition of 10 ng/ml of recombinant IL-4, IL-10, TGF-beta, or their combination (for all, p<0.05). Among anergic donors, addition of 10 ng/ml of anti-IL-10 significantly increased IFN-gamma production (p<0.05), but addition of anti-IL-4 or anti-TGF-beta did not. Among immune donors, the percent of both CD3 lymphocytes and NK cells expressing IFN-gamma after 24h of T27K was increased above control (p<0.05), while the percent of NK cells producing TNF-alpha in response to T27K was not greater than control. Depletion of NK cells from peripheral blood mononuclear cells resulted in significant increases in TNF-alpha and IL-10 (for both, p<0.05) but resulted in no significant decrease in IFN-gamma or IL-2. These data demonstrate a differential response to stimulation with the coccidioidal antigen T27K among donors with coccidioidomycosis that can be manipulated by cell type and cytokine environment.

Antigens, Protozoan↗

PubMed1981

Disseminated coccidioidomycosis in children.

In an effort to define the importance of extrapulmonary coccidioidomycosis in the pediatric age group, we have studied 14 cases and reviewed the literature. The available data suggest that children are as susceptible to dissemination as are adults. Most children with disseminated coccidioidomycosis have evidence, either by history or chest radiographs, of preceding or concurrent pulmonary infection. The most common sites of dissemination are skin, subcutaneous tissue, bone, and meninges. Coccidioides immitis may be detected in tissues or body secretions by microscopic examination or by appropriate culture. Serologic tests are also useful in making the diagnosis and in following the course of the infection. Skin tests are often negative. Infection is progressive in 60% without antifungal therapy. Coccidioidomycosis of bone, skin, or subcutaneous tissue can be managed effectively with combined surgical and antifungal therapy. Meningitis is much more difficult to treat and is fatal in 50% of cases even when treated with amphotericin B.

Adolescent↗