Atypical Pleural Effusion in an Immunocompetent Patient With Valley Fever: A Case Study and Review of the Literature.

Valley fever is a fungal infection, commonly of the lungs, caused by Coccidioides immitis or Coccidioides posadasii. This disease is endemic to the southwestern United States, Central America, and South America. Infected individuals are typically asymptomatic but may develop community-acquired pneumonia. On rare occasions, coccidioidomycosis can present with severe complications in addition to the pulmonary manifestation. In this study, a 58-year-old immunocompetent male presented to the Emergency Department with a cough, night sweats, and pleuritic chest pain. Despite the administration of broad-spectrum antimicrobials, he developed a large right pleural effusion that did not resolve following thoracentesis. Serology was positive for Coccidioides, and the patient was referred to a thoracic surgeon due to persistent effusion. It is rare for patients with coccidiomycosis to develop a large pleural effusion requiring surgical intervention, especially in immunocompetent individuals. This case highlights the importance of monitoring patients with unresolved acute pneumonia in endemic areas and considering Coccidioides as a possible etiology.

Pulmonary coccidioidomycosis mimicking malignancy associated with Sweet's syndrome (acute febrile neutrophilic dermatosis).

A suspicious malignant lung nodule with cutaneous reaction is not always cancer, especially in low risk for malignancy patients. A lung biopsy should be taken into consideration. The associated cause of Sweet's syndrome directs the treatment in each patient.

Utility of multimodal sampling and testing during advanced bronchoscopy for diagnosing atypical respiratory infections in a Coccidioides-endemic region.

Background: The role of advanced diagnostic bronchoscopy (ADB) for assessing atypical respiratory infections is unclear. The purpose of this study was to ascertain: (I) the diagnostic utility of ADB-tissue sampling in patients with focal thoracic lesions due to atypical respiratory infections; (II) how multimodal bronchoscopic sampling and testing enhance diagnosis in a Coccidioides-endemic region. Methods: A retrospective observational cohort study analyzing all ADBs performed over a 10-year period in patients with focal thoracic lesions diagnosed with a non-malignant disorder. Only cases which procured lower respiratory tract secretion and tissue samples by ADB, and had both cytohistology and culture results available were included. Results: Among 403 subjects with non-malignant disease, 136 (33.7%) were diagnosed with atypical respiratory infections, with ADB contributing a diagnosis in 119 (87.5%) of these. Coccidioidal disease was independently associated with a cytohistologic diagnosis [odds ratio =7.64, 95% confidence interval (CI): 2.51-23.26; P<0.001]. Mycobacteria were more effectively identified by culture (overall yield of 8.4%, vs. 2.7% by cytohistology; P<0.001). Among subjects for which both respiratory secretion and tissue sampling were dual-tested with culture and cytology/cytohistology, adding ADB-guided transbronchial needle aspiration and/or forceps biopsy (TBNA/TBFB) to bronchoalveolar lavage and/or bronchial washings (BAL/BW) more than doubled the yield for dimorphic fungi, from 7.1% to 15.1% (increase of 8.0%, 95% CI: 5.2-11.9%). For lung lesions, adding tissue culture to dual TBNA/TBFB cytohistology-tested lung samples doubled the proportion diagnosed with atypical infection over using TBNA-cytohistology alone (increase of 15.8%, 95% CI: 10.4-23.1%). Adding lymph node to lung sampling increased the proportion diagnosed with coccidioidomycosis by 8.8% (95% CI: 4.8-15%). Among subjects with atypical respiratory infections, major ADB-related complications occurred in 1.5%. Conclusions: ADB is useful for diagnosing atypical respiratory infections manifesting as focal thoracic lesions. A multimodal approach to both sampling and testing enhances yield, while maintaining a favorable procedure safety profile. Cytohistology testing and nodal sampling are beneficial for pulmonary coccidioidomycosis, and culture for mycobacterial disease. The approach to ADB-sampling should be adjusted according to clinical context and regional infection patterns.

Serologic Rebound after Stopping Azoles for Primary Pulmonary Coccidioidomycosis: A Case-Controlled Observational Study.

BACKGROUND: We sought to characterize the outcomes of patients with primary pulmonary coccidioidomycosis whose post-treatment complement fixation (CF) titer increased by more than 2 dilutions (serologic rebound) after discontinuation of antifungal treatment. METHODS: We conducted a retrospective chart review of patients with primary pulmonary coccidioidomycosis and identified immunocompetent, non-pregnant adults who received antifungal treatment and then experienced a serologic rebound after treatment discontinuation. We compared these to matched controls similarly treated who did not have serologic rebound. RESULTS: Fifty-eight patients experienced serologic rebound. Thirty (52%) of these were associated with symptoms. Nine were associated with radiographic progression. The median time to serologic rebound was 3.5 months. Antifungal treatment was reinitiated in 37 (63.7%) patients. Four of the 58 (6.9%) with rebounded serology subsequently developed extra-thoracic dissemination. Compared with matched controls, patients with rebounded serology were more likely to have post-treatment symptoms, reinitiation of antifungal therapy, and a longer duration of clinical follow-up. However, they were not more likely to experience extra-thoracic dissemination. CONCLUSION: Serological rebound, manifested in at least 2-dilution rise of CF titer following antifungal treatment of primary pulmonary coccidioidomycosis, was uncommon, but resulted in longer clinical follow-up. Continued monitoring of such patients is important to identify the patients who develop subsequent symptoms, as well as extra-thoracic dissemination.

Differentiating Lung Nodules Due to Coccidioides from Those Due to Lung Cancer Based on Radiographic Appearance.

BACKGROUND: Coccidioidomycosis (cocci) is an endemic fungal disease that can cause asymptomatic or post-symptomatic lung nodules which are visible on chest CT scanning. Lung nodules are common and can represent early lung cancer. Differentiating lung nodules due to cocci from those due to lung cancer can be difficult and lead to invasive and expensive evaluations. MATERIALS AND METHODS: We identified 302 patients with biopsy-proven cocci or bronchogenic carcinoma seen in our multidisciplinary nodule clinic. Two experienced radiologists who were blinded to the diagnosis read the chest CT scans and identified radiographic characteristics to determine their utility in differentiating lung cancer nodules from those due to cocci. RESULTS: Using univariate analysis, we identified several radiographic findings that differed between lung cancer and cocci infection. We then entered these variables along with age and gender into a multivariate model and found that age, nodule diameter, nodule cavitation, presence of satellite nodules and radiographic presence of chronic lung disease differed significantly between the two diagnoses. Three findings, cavitary nodules, satellite nodules and chronic lung disease, have sufficient discrimination to potentially be useful in clinical decision-making. CONCLUSIONS: Careful evaluation of the three obtained radiographic findings can significantly improve our ability to differentiate benign coccidioidomycosis infection from lung cancer in an endemic region for the fungal disease. Using these data may significantly reduce the cost and risk associated with distinguishing the cause of lung nodules in these patients by preventing unnecessary invasive studies.

Diagnosing Pulmonary Embolism Using Point-of-Care Ultrasound in a Patient With Malingering and Coccidioidomycosis Infection.

We report a case of a 41-year-old male diagnosed with pulmonary coccidioidomycosis and pulmonary embolism (PE) based on a point-of-care ultrasound (POCUS) finding who was suspected to be malingering for right-sided chest pain considering his psychiatric history. POCUS was performed and showed right ventricular strain with a D-shaped left ventricle and B-lines with subpleural consolidations, and PE was confirmed with computed tomography pulmonary angiography. No other risk factors for PE were found except for coccidioidomycosis. The patient was treated with apixaban and fluconazole and discharged in stable condition. We discuss the usefulness of POCUS in diagnosing PE and the very rare association between coccidioidomycosis and PE.

Natural history of pulmonary coccidioidomycosis: Further examination of the VA-Armed Forces Database.

There are still many limitations related to the understanding of the natural history of differing forms of coccidioidomycosis (CM), including characterizing the spectrum of pulmonary disease. The historical Veterans Administration-Armed Forces database, recorded primarily before the advent of antifungal therapy, presents an opportunity to characterize the natural history of pulmonary CM. We performed a retrospective cohort study of 342 armed forces service members who were diagnosed with pulmonary CM at VA facilities between 1955 to 1958, followed through 1966, who did not receive antifungal therapy. Patients were grouped by predominant pulmonary finding on chest radiographs. The all-cause mortality was low for all patients (4.6%). Cavities had a median size of 3-3.9 cm (IQR: 2-2.9-4-4.9 cm), with heterogeneous wall thickness and no fluid level, while nodules had a median size of 1-1.19 cm (Interquartile range [IQR] 1-1.9-2-2.9 cm) and sharp borders. The majority of cavities were chronic (85.6%), and just under half were found incidentally. Median complement fixation titers in both the nodular and cavitary groups were negative, with higher titers in the cavitary group overall. This retrospective cohort study of non-disseminated coccidioidomycosis, the largest to date, sheds light on the natural history, serologic markers, and radiologic characteristics of this understudied disease. These findings have implications for the evaluation and management of CM.

Coccidioidomycosis (CM), also known as San Joaquin Valley Fever, causes a variety of symptoms including pneumonia. This historical study investigates CM of the lungs in American soldiers with CM in the 1950s, prior to modern antifungals, to better understand the natural history.

Disseminated Coccidioidomycosis in an Immunocompetent Male Who Lived in an Endemic Region in the Remote Past: A Case Report.

Coccidioidomycosis is an endemic illness suspected in patients who live in or have recently traveled to an endemic area. Disseminated disease is less frequent and is almost always seen in the presence of risk factors such as immunosuppression. We present a case of disseminated coccidioidomycosis with a delayed presentation in a young immunocompetent male. The patient developed symptoms two years after migrating from the endemic region of Mexico. He presented with fever, cough, and shortness of breath for two weeks. Chest imaging revealed left-sided consolidation and pleural effusion. Empyema was ruled out by thoracentesis. The patient did not improve with antibiotics for community-acquired pneumonia. A comprehensive microbiological workup for bacterial, viral, mycobacterial, and fungal etiologies, including cultures of several specimens of sputum, pleural fluid, blood, bronchoalveolar lavage, serological tests (initial), and transbronchial lung biopsy, was nondiagnostic. The patient continued to have fever and shortness of breath despite the escalation of antibiotic coverage to broad-spectrum. The patient underwent an open surgical lung biopsy, and the diagnosis of coccidioidomycosis was ultimately established by histopathological examination of lung and pleural specimen which showed spherules of Coccidioides sp. The patient developed worsening headaches, a lumbar puncture was done and cerebrospinal fluid revealed coccidioidal antibody which confirmed meningeal dissemination. Human immunodeficiency virus/acquired immunodeficiency syndrome or other immunosuppressed state was not identified in the patient. Notably, the second set of antibody titers collected two weeks after the initial negative set of titers returned strongly positive. The patient was started on fluconazole but did not show clinical improvement and was switched to amphotericin B. Subsequently, the patient improved and was discharged on lifelong oral fluconazole with close outpatient clinical and serological monitoring. He has had no signs of relapse during the last 20 months.

Pandora's Box: Disseminated Coccidioidomycosis Associated with Self-Medication with an Unregulated Potent Corticosteroid Acquired in Mexico.

Coccidioidomycosis (CM), caused by the dimorphic fungi Coccidioides immitis and C. posadasii, typically presents as acute or chronic pulmonary disease. However, disseminated disease occurs in about 1% of patients. Disseminated CM may affect multiple organ systems, including cutaneous, osteoarticular, and central nervous system sites. Here, we present a case of disseminated CM in a patient from a border city in Texas. The patient had a history of uncontrolled diabetes mellitus and was also taking an over-the-counter medication acquired in Mexico that contained a potent corticosteroid. The patient presented with seizures and was found to have a brain infarct, cavitary lung lesions, synovitis of the knee, multiple skin lesions, and chorioretinitis. The patient had a very high complement fixation titer for Coccidioides; fungal spherules were seen in a skin biopsy specimen, and Coccidioides grew in culture from a sample of synovial fluid and the skin biopsy specimen. This case illustrates the dissemination potential of Coccidioides, the danger of unregulated pharmaceuticals, the importance of thorough history taking, and recognizing risk factors that contribute to disseminated CM.

Disseminated Coccidioidomycosis Following Insufficient Treatment at Initial Presentation: Case Report.

A 35-year-old male presented to our university hospital with night sweats, fevers, ulcerated skin lesions to the lower mouth and posterior neck, shortness of breath, and an enlarging cervical lymph node. The patient was evaluated 2 months prior for respiratory symptoms, cervical lymphadenopathy, and skin lesions resulting in a diagnosis of primary pulmonary coccidioidomycosis and was treated with a 4-week course of fluconazole. On presentation to our hospital, initial laboratory test results revealed leukocytosis, increased liver enzymes, elevated inflammatory markers, and hypercalcemia. Computed tomography scan of the chest revealed lung nodules in a miliary pattern and prominent mediastinal lymphadenopathy. Magnetic resonance imaging revealed multiple vertebral and iliac bone lesions, as well as bilateral psoas muscle lesions. Serum ELISA (enzyme linked immunosorbent assay) detected elevated serological markers against coccidioides, and sputum culture revealed coccidioides arthroconidia, confirming the presence of an acute coccidioides infection. Biopsy of the right iliac crest and cervical lymph node revealed spherules resembling coccidioides, escalating the diagnosis to disseminated coccidioidomycosis. The patient's hospital course was complicated by septic shock, acute respiratory distress syndrome requiring several days of mechanical ventilation, and acute kidney injury. He was ultimately treated with several weeks of voriconazole and liposomal amphotericin-B. He made a full recovery and was discharged on an extended course of oral voriconazole. Our case highlights the importance of recognition and appropriate treatment duration of disseminated coccidioidomycosis at initial presentation. Failure to do so may lead to increased morbidity and mortality.

The Coincidence of 2 Epidemics, Coccidioidomycosis and SARS-CoV-2: A Case Report.

In the middle of a pandemic, patients with cough and fever are thought to have SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2). It should be remembered that in the desert southwest of the United States, we have an ongoing epidemic of coccidioidomycosis (CM). There are additionally many other respiratory illnesses that could be confused with CoV-2 or overlooked. This is a case report of CoV-2 engrafted on chronic cavitary pulmonary CM. In a time where the coronavirus pandemic is becoming rampant, we demonstrate the case of a coinfection with cavitary pulmonary CM. In this case, the importance of detection of the coronavirus and treatment of the coinfection is explored.

Pulmonary Coccidioidomycosis Mimicking Aspergillosis Fungus Ball.

The genus Coccidioides is composed of C. immitis and C. posadasii. Both can cause coccidioidomycosis and are geographically restricted to certain areas of endemicity. The histopathologic features in pulmonary coccidioidomycosis include necrotizing granulomatous inflammation and the presence of spherules, which is considered to be a key diagnostic finding. Cavitary lung disease containing a fungal ball with branching septate hyphae is an unusual funding in pulmonary coccidioidomycosis but is typical for aspergillosis. We present a case of 42 year old man who underwent wedge resection of the lung for a persistent cavitary lesion. The microscopic examination shows a fungal ball composed of acute-angle branching septate hyphae, consistent with a diagnosis of aspergillosis. However, cultures and molecular testing by DNA sequencing of the 28S ribosomal DNA gene confirmed the identification of C. posadasii. This finding highlights the importance of exposure history and organism identification by either conventional cultivation or molecular testing in rendering an accurate diagnosis.

A Case of Refractory Pulmonary Coccidioidomycosis Successfully Treated with Posaconazole Therapy.

Coccidioidomycosis is an endemic fungal infection caused by the inhalation of the spores of Coccidioides species. Patients with underlying immunosuppressive illness can contract chronic or disseminated disease which requires prolonged systemic therapy. Pulmonary coccidioidomycosis remains as an illusory and abstruse disease, with increased prevalence that poses as a challenge for clinicians in developing an effective strategy for treatment. Here, we report successful treatment of a refractory case of chronic relapsing pulmonary coccidioidomycosis in a 50-year old woman with a thin-walled cavitary lung lesion who was ultimately treated with posaconazole.

Coccidioidomycosis: Experience From a Children's Hospital in an Area of Endemicity.

The incidence of coccidioidomycosis is increasing, and published pediatric experience is limited. This study further characterizes pediatric coccidioidomycosis by describing experience with 64 patients cared for at Children's Hospital of Los Angeles over 20 years, with focus on sites of involvement and severity, as well as serologic profiles of affected children.

Acute Pulmonary Coccidioidomycosis and Review of Published Cases with Lung Involvement in Korea

Coccidioidomycosis is a fungal infection caused by Coccidioides immitis. The endemic area is mostly south-western United States. As increasing in overseas travel to endemic areas, the incidence rate has been recently increased in non-endemic areas. The diagnosis may be delayed in non-endemic area. It is important to elicit traveling histories and to differentiate lung consolidation with eosinophilia, for timely diagnosis of coccidioidomycosis. Recently, we experienced a case with pulmonary coccidioidomycosis in a Korean American who visited Korea showed consolidation in right lower lobe on chest X-ray and prolonged eosinophilia. In the case, a confirmatory diagnostic method was percutaneous transthoracic needle biopsy of lung. We report acute pulomonary coccidioidomycosis case and review previous published reports with pulmonary manifestation in Korea.

Characteristics of patients with mild to moderate primary pulmonary coccidioidomycosis.

In Arizona, USA, primary pulmonary coccidioidomycosis accounts for 15%-29% of community-acquired pneumonia. To determine the evolution of symptoms and changes in laboratory values for patients with mild to moderate coccidioidomycosis during 2010-2012, we conducted a prospective 24-week study of patients with primary pulmonary coccidioidomycosis. Of the 36 patients, 16 (44%) were men and 33 (92%) were White. Median age was 53 years, and 20 (56%) had received antifungal treatment at baseline. Symptom scores were higher for patients who received treatment than for those who did not. Median times from symptom onset to 50% reduction and to complete resolution for patients in treatment and nontreatment groups were 9.9 and 9.1 weeks, and 18.7 and 17.8 weeks, respectively. Median times to full return to work were 8.4 and 5.7 weeks, respectively. One patient who received treatment experienced disseminated infection. For otherwise healthy adults with acute coccidioidomycosis, convalescence was prolonged, regardless of whether they received antifungal treatment.

Coccidioidomicosis: Más que una enfermedad regional / Coccidioidomycosis: More than a regional disease

La coccidioidomicosis es causada por dos especies casi idénticas de un hongo dimórfico, el Coccidioides immitis y el C. posadasii. Es endémica en las zonas semiáridas del continente americano, especialmente en el sur de los Estados Unidos de Norteamérica y en el norte de México, pero existen regiones endémicas bien definidas en Centro y Sudamérica; ocasionalmente se diagnostica fuera de las áreas endémicas. En México, la mayoría de los reportes de casos clínicos provienen del norte del país. Sin embargo, su incidencia real se desconoce porque no es una enfermedad de reporte obligatorio. Más del 60% de las infecciones primarias son asintomáticas; en el resto, la presentación típica se caracteriza por síntomas y signos generales, dermatológicos y respiratorios ("'Fiebre del Valle "). La presentación pulmonar aguda suele ser indistinguible de la neumonía bacteriana adquirida en la comunidad. La coccidioidomicosis extrapulmonar se presenta en uno de cada 200 sujetos infectados; los sitios más comúnmente afectados son meninges, huesos, articulaciones, piel y tejidos blandos. El diagnóstico se basa en el aislamiento del hongo por cultivo. La presencia de esférulas en secreciones y tejidos se considera también como criterio diagnóstico. Se dispone de pruebas serológicas para el diagnóstico. La coccidioidomicosis incluye un espectro de presentaciones que van desde la primoinfección no complicada, que es autolimitada y se resuelve sin tratamiento hasta en el 95% de los casos, hasta las formas diseminadas agudas casi siempre fatales a pesar de tratamiento, por lo que las estrategias terapéuticas varían considerablemente de un paciente a otro. Los antimicóticos más utilizados son la amfotericina B, el fluconazol y el itraconazol.

Coccidioidomycosis is a fungal disease caused by two nearly identical species, Coccidioides immitis and C. posadasii. It is endemic in the semiarid zones of the western hemisphere, especially in the southern United States of America and northern Mexico, although there are definite endemic regions in Central and South America; occasionally, it is diagnosed outside the endemic areas. In México most of the reported cases come from the northern states; however, not being a reportable disease, its true incidence is unknown. More than 60 percent of the primary infections are asymptomatic; in the rest, the typical presentation includes systemic, dermatologic and respiratory signs and symptoms ("Valley Fever"). The acute pulmonary presentation is indistinguishable from a community acquired bacterial pneumonia. Extrapulmonary coccidioidomycosis occurs in one out of 200 primary infections. The most commonly affected sites include the central nervous system, bone, joints, skin and soft tissues. Diagnosis is based in the isolation of the fungus by culture; direct observation of the spherules in exudates or in tissue is also considered diagnostic. There are serologic essays available for diagnosis. Coccidioidomycosis includes a wide spectrum of clinical presentations, from the primary non complicated self-limited infection that usually resolves without specific treatment, to the acute disseminated forms usually fatal despite therapy. For this reason, the therapeutic strategies vary considerably from patient to patient. The most frequently used antimycotic drugs are amphotericin B, itraconazole and fluconazole.