"It's Not Just Bacteria": A Cavitary Lung Lesion in a Patient Living in the Coachella Valley.

Cavitary pulmonary coccidioidomycosis is rare diagnosis with an incidence of 13% to 15% of pulmonary coccidioidomycosis cases. High clinical suspicion is necessary in the setting of geographical location endemicity. We present a 49-year-old male who has lived in the Coachella Valley of California for several years, with a medical history of uncontrolled type 2 diabetes who noted 1 week of right-sided chest pain with shortness of breath, fever, chills, night sweats, and weight loss. A chest X-ray revealed a 4- to 5-cm mass in the right lung. Initial workup revealed negative sputum cultures (aerobic/anaerobic, acid-fast bacilli). However, dedicated fungal cultures (samples from sputum, lymph nodes, lung right lower lobe bronchial swabs), bronchial washings, and surgical tissue biopsy of the right lower lobe revealed mold. The patient underwent right thoracotomy with right lower lobectomy and right mediastinal lymph node dissection for both diagnostic (lung specimen) and therapeutic (removing necrotic lung tissue, source control) purposes. Finally, serum Coccidioides antigens were positive and antibody titers were positive at 1:8; surgical biopsy of the right lower lobe grew mold that came back positive for Coccidioides posadasii. Targeted pharmacotherapy was commenced using intravenous fluconazole and then oral fluconazole for 3 months was prescribed upon discharge. The patient had gradual improvement of his shortness of breath and was instructed to follow-up at an infectious disease clinic.

What You See Is Not What You Get: Germ Cell Tumor Mimicking Disseminated Coccidioidomycosis.

We present the case of a 30-year-old man with no prior medical history who presented to the hospital with a myriad of symptoms such as shortness of breath, generalized weakness, lower limb weakness, and urinary retention. He was recently diagnosed with "disseminated coccidioidomycosis" by an outside provider on an outpatient basis and started on fluconazole orally. However, due to a lack of improvement and significant symptoms, he was sent to the hospital to initiate liposomal amphotericin B treatment. After a comprehensive workup, an alternative diagnosis was suspected and eventually confirmed as metastatic germ cell carcinoma. Due to the vast dissemination and his poor functional status despite chemotherapy initiation, the patient elected for palliative care and expired shortly after at hospice. This case demonstrates the similarity of clinical findings between disseminated infections and malignancies.

Coccidioidomycosis lymphadenopathy: an unusual presentation.

Coccidioidomycosis is known to occur around the western hemisphere. In tropical countries, the clinical presentation is atypical presenting with a superficial abscess preceded by respiratory tract involvement often mimicking tuberculosis. Eliciting a history of exposure and high suspicion is imperative for early diagnosis.In the present case report, a man in his early 30s presented with complaints of swelling over the neck for the past 2 months with a recent travel history. With a provisional clinical diagnosis of tuberculosis, a biopsy of the swelling revealed features of granulomas with non-caseating necrosis with Coccidioidomycosis organisms demonstrated by fungal stains. Fungal culture and serology reiterated Coccidioides and he recovered after a course of fluconazole.The case report concludes with a statement that Coccidioidomycosis is known to manifest with lymphadenitis mimicking tuberculosis and must be taken into account as one of the differentials. The current report is presented for its rarity in India with atypical presentation.

Coccidioidomycosis where you least expect it.

An elderly man without history of travel presented with complaints of intermittent fever for 2 months, cough with scanty expectoration for 15 days and history of weight loss of 5 kg in 1 year. The chest X-ray and CT scan of the thorax showed dispersed centrilobular nodules and patchy subpleural consolidation in both lungs with mediastinal lymphadenopathy. He underwent bronchoscopy and bronchoalveolar lavage culture grew Pseudomonas aeruginosa He was prescribed antibiotics based on culture sensitivity; however, patient continued to have symptoms. All relevant blood investigations were within normal limits. He underwent CT-guided biopsy of the right lung lesion during which clearing of the radio-opacities present in the initial CT scan and appearance of fresh lesions in different locations were observed. Migratory shadows were suspected. Fine-needle aspiration cytology showed features suggestive of coccidioidomycosis for which antifungals were started. After 1 month, he improved symptomatically and chest X-ray showed clearance of shadows.

Clinical characteristics, magnetic resonance imaging features, treatment, and outcome for presumed intracranial coccidioidomycosis in 45 dogs (2009-2019).

BACKGROUND: Knowledge of the clinical and magnetic resonance imaging (MRI) features of intracranial Coccidioides infection in dogs is essential for prompt diagnosis to limit disease-associated morbidity and death. OBJECTIVES: To describe the MRI appearance of intracranial coccidioidomycosis in dogs, identify associated clinical and clinicopathologic findings, and report outcomes of medical treatment. ANIMALS: Forty-five client-owned dogs with presumed intracranial Coccidioides infection. METHODS: Retrospective case series. Medical records and images were reviewed. Clinical history, examination findings, serology, imaging characteristics, treatment, and outcome were recorded. Included cases had an abnormal brain MRI and positive Coccidioides serology by agar-gel-immunodiffusion (AGID). RESULTS: Median age was 7-years. Generalized tonic-clonic seizures were the most common presenting sign (25/45). Two lesion categories were identified: a granulomatous form with 1 or more distinct, intra-axial, contrast-enhancing foci (37/45), and a second variation with diffuse, bilateral, symmetrical lesions of the caudate nuclei and frontal lobes (8/45). Serum IgG titers ranged from 1 : 1 to ≥ 1 : 256; 2 dogs had positive IgM titers at 1 : 2. All dogs with follow-up serology (34/45) had a reduction in titer. Mean duration of follow-up was 22.4 ± 20.5 months (median 16 months). Six dogs were lost to follow-up <1-year after diagnosis (median 9 months). Five dogs were clinically well but had yet to be followed for >1-year. Of the remaining 34 dogs, 28 (82%) were alive ≥ 1-year after diagnosis. Thirteen of these dogs had follow-up times ≥ 2-years. CONCLUSIONS AND CLINICAL IMPORTANCE: The prognosis for intracranial Coccidioides infection is generally more favorable with medical treatment than in earlier reports.

Disseminated coccidioidomycosis in a patient with juvenile idiopathic arthritis receiving infliximab.

BACKGROUND: Coccidioides immitis is a dimorphic fungus endemic to the arid climates of the Southwest United States, Mexico and parts of Central and South America. Human infection occurs through inhalation of spores with less than half of exposures progressing to a symptomatic state that primarily consists of pulmonary manifestations. Disseminated coccidioidomycosis is exceedingly rare, occurring in fewer than 1 % of symptomatic infections. Through hematogenous spread, the fungus can infect most organ systems and may be fatal without systemic antifungal treatment. Individuals with impaired cell-mediated immunity either from primary immunodeficiency disorders or secondary to immunosuppression with medications such as tumor necrosis factor alpha (TNF-α) inhibitors have increased risk of disseminated coccidioidomycosis and previous cases of coccidioidomycosis have been reported with biologic therapy. CASE PRESENTATION: We present a case of disseminated coccidioidomycosis in a 16-year-old female with polyarticular juvenile idiopathic arthritis (JIA) being treated with prednisone, methotrexate, and infliximab. The patient presented with symptoms of meningeal irritation, bilateral choroidal lesions, and necrotizing peripheral pneumonia. Her infection was thought to be a reactivation of coccidioidomycosis given her history of resolved pneumonia that occurred after traveling to Arizona, New Mexico, and El Paso one year prior to presentation. Following diagnosis, she improved with discontinuation of her immunosuppressive medications and two weeks of intravenous amphotericin B and fluconazole with plans for lifetime treatment with fluconazole while immunosuppressed. Due to worsening arthritis, she will begin tofacitinib and continue close monitoring of chest x-rays and coccidioides antibody. CONCLUSIONS: Patients undergoing immunosuppressive therapy for rheumatological conditions are at increased risk of disseminated coccidioidomycosis and should be evaluated with high suspicion when presenting with atypical symptoms and history of travel to endemic regions.

Cavitary Coccidioidomycosis: Impact of azole antifungal therapy.

Approximately 5 to 15% of patients with pulmonary coccidioidomycosis subsequently develop pulmonary cavities. These cavities may resolve spontaneously over a number of years; however, some cavities never close, and a small proportion causes complications such as hemorrhage, pneumothorax or empyema. The impact of azole antifungal treatment on coccidioidal cavities has not been studied. Because azoles are a common treatment for symptomatic pulmonary coccidioidomycosis, we aimed to assess the impact of azole therapy on cavity closure. From January 1, 2004, through December 31, 2014, we retrospectively identified 313 patients with cavitary coccidioidomycosis and excluded 42 who had the cavity removed surgically, leaving 271 data sets available for study. Of the 271 patients, 221 (81.5%) received azole therapy during 5-year follow-up; 50 patients did not receive antifungal treatment. Among the 271 patients, cavities closed in 38 (14.0%). Statistical modeling showed that cavities were more likely to close in patients in the treated group than in the nontreated group (hazard ratio, 2.14 [95% CI: 1.45-5.66]). Cavities were less likely to close in active smokers than nonsmokers (11/41 [26.8%] vs 97/182 [53.3%]; P = 0.002) or in persons with than without diabetes (27/74 [36.5%] vs 81/149 [54.4%]; P = 0.01).We did not find an association between cavity size and closure. Our findings provide rationale for further study of treatment protocols in this subset of patients with coccidioidomycosis. LAY SUMMARY: Coccidioidomycosis, known as valley fever, is a fungal infection that infrequently causes cavities to form in the lungs, which potentially results in long-term lung symptoms. We learned that cavities closed more often in persons who received antifungal drugs, but most cavities never closed completely.

TNFα Blockade Inhibits Both Initial and Continued Control of Pulmonary Coccidioides.

Tumor necrosis factor alpha (TNFα) is a pluripotent cytokine that is important in many infections, though its role in Coccidioides infection remains poorly understood. The need to understand TNFα in Coccidioides infection has increased recently with the widespread use of TNFα inhibitors for a wide variety of autoimmune conditions. Here, we couple the newly developed Coccidioides infection model using strain Cp1038 and C57BL/6 × DBA/2J F1 (B6D2F1) mice. B6D2F1 mice develop long-lasting control of Cp1038. Treatment of B6D2F1 mice with anti-TNFα antibodies permits significant fungal proliferation and death. Additionally, we show that antibody treatment limited to the first 2 weeks of infection was sufficient to induce this same loss of fungal control. Importantly, anti-TNFα antibody treatment initiated after fungal control leads to a loss of host control. These results highlight the importance of TNFα in both the initial control of murine Coccidioides and ongoing suppression of the fungal disease.

An Acute Pulmonary Coccidioidomycosis Coinfection in a Patient Presenting With Multifocal Pneumonia With COVID-19.

The ongoing coronavirus disease-2019 (COVID-19) pandemic has been the focus of health care workers as it has affected millions of people and cost hundreds of thousands of lives around the world. As hospitals struggle to identify and care for those afflicted with COVID-19, it is easy to overlook endemic diseases that potentially worsen or mimic the pulmonary manifestations or may coinfect those with COVID-19. In this case report, we present the case of a 48-year-old Hispanic female who was admitted with respiratory distress from an acute COVID-19 infection but was also found to have acute pulmonary coccidioidomycosis infection and was treated successfully.

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.

Simultaneous coccidioidomycosis and phaeohyphomycosis in a kidney transplant recipient: A case report and literature review.

Advances in solid organ transplantation have improved the survival of end-stage organ disease at the expense of an increased risk for opportunistic infections. Unusual clinical presentations and the possibility of concurrent infections make diagnosing invasive fungal infection (IFI) more difficult. Here, we present a case of simultaneous vertebral infection caused by Coccidioides immitis-posadasii and subcutaneous phaeohyphomycosis due to Nigrograna mackinnonii in a kidney transplant recipient. The diagnosis of both infections required invasive procedures to obtain tissue and a high index of suspicion that more than one IFI could be present. A multidisciplinary team approach for the management of immunocompromised patients with suspected or diagnosed IFI is warranted.

Opportunistic coinfection with Pneumocystis jirovecii and Coccidioides immitis associated with idelalisib treatment in a patient with chronic lymphocytic leukaemia.

We describe a case of opportunistic coinfections with Coccidioides immitis and Pneumocystis jirovecii following treatment with idelalisib, a phosphoinositide 3-kinase inhibitor, for chronic lymphocytic leukaemia. This is the first case of pulmonary coccidioidomycosis reported in association with idelalisib. We review challenges related to diagnosis of opportunistic infections in this context. This report illustrates (1) the uncommon occurrence of two opportunistic infections concurrently or in rapid succession, (2) the importance of maintaining a broad differential diagnosis in the setting of an atypical imaging finding, slow clinical response or when immunomodulatory drugs are used, and (3) the challenges associated with non-invasive serological testing in individuals with haematological malignancy on immunomodulatory therapy.

Coccidioides in lung transplant: case report.

A middle-aged woman was hospitalised for generalised, painful skin lesions 6 weeks after a successful double-lung transplant. She had end-stage lung disease associated with chronic obstructive pulmonary disease due to alpha-1 antitrypsin deficiency, and she had been treated with itraconazole for 16 months because of lung infection associated with Malbranchea spp. Results of a skin biopsy of the initial lesion on her arm showed non-specific dermal inflammation, presumably due to reactivation of the Malbranchea spp infection. Follow-up cervical lymph node biopsy and culture showed Coccidioides posadasii/C. immitis A detailed review of her travel history showed a 4-month stay in Arizona as a teenager that she barely remembered. Coccidioides spp were likely misidentified as Malbranchea spp owing to similar morphological characteristics. Dosages of immunosuppressive medications were reduced, and antifungal therapy was changed to posaconazole. Her skin lesions resolved.

Coccidioidomycosis in a reference center in Northeast Brazil: clinical/epidemiological profile and most common radiological findings

Abstract INTRODUCTION: Coccidioidomycosis, a disease caused by Coccidioides immitis or Coccidioides posadasii, is endemic in arid climatic regions in Northeast Brazil. Its prevalence is higher among young adult males living in rural areas. Existing literature about this disease in Ceará, a Northeast Brazilian state, are scarce. Here, we aimed to outline the clinical and epidemiological profiles, radiological patterns, and therapeutic responses of patients with coccidioidomycosis in a reference center in Ceará, Brazil. METHODS This is a descriptive study with quantitative analysis. Patients who underwent medical follow-up in São José Hospital of Infectious Diseases and received confirmed mycological diagnosis of coccidioidomycosis between January, 2007 and December 2017 were included. Epidemiological, clinical, radiological, and therapeutic response data were collected from medical charts. RESULTS Thirty patients were included. The patients were males with median age of 30 years, and 73% were considered to have high-risk exposure to Coccidioides owing to professional activities. Cough (96.7%), dyspnea (63.3%), fever (86.7%), and pleuritic pain (60%) were the most prevalent clinical manifestations. Interstitial pattern (91.3%) was the most frequent pulmonary radiological finding. Fluconazole, amphotericin B, and itraconazole were administered for treatment (in 82.1%, 42.8%, and 21.4% of cases, respectively). A favorable outcome was observed in 83.8% of patients. CONCLUSIONS Coccidioidomycosis was more prevalent in the central and southern regions of the State of Ceará. Understanding the local epidemiology and clinical manifestations of the disease, in addition to the pulmonary radiologic findings, may aid the early detection of coccidioidomycosis and facilitate early diagnosis.

Selected Clinical Features of Coccidioidomycosis in Dogs.

Canine coccidioidomycosis, a systemic fungal infection endemic to arid and semiarid regions of North, Central, and South America, is commonly diagnosed in dogs living in or traveling through lower Sonoran life zones in the states of California and Arizona. Canine and human cases have geographic overlap. Similarities between clinical coccidioidomycosis in dogs and humans include asymptomatic infection, primary respiratory disease and disseminated disease. Differences include a high rate of dissemination in dogs, differences in predilection of dissemination sites, and a granulomatous or diffuse meningoencephalopathic form in the canine central nervous system (CNS) without the obstructive component seen in humans. Dogs presenting with CNS coccidioidomycosis most commonly experience seizures. Prior disease history and serology are unreliable indicators of CNS coccidioidomycosis. Magnetic resonance imaging (MRI) is advantageous for diagnosis of CNS coccidioidomycosis in dogs. Long-term administration of antifungal medication is promoted for treatment of both primary and disseminated coccidioidomycosis in dogs. Supportive treatment addressing pain, fever, inappetance, coughing, and other clinical signs improves patient care. Glucocorticoids and or anticonvulsants are also recommended for canine disseminated CNS disease. Protracted treatment times, lack of owner compliance, failure of the disease to respond to the first antifungal drug selected, and high cost are challenges of successfully treating dogs.

Coccidioidomycosis: What a long strange trip it's been.

The recorded history of coccidioidomycosis began in 1892 with the report of the illness of Domingo Escurra by Alejandro Posadas followed by a description of the first North American cases by Rixford and Gilchrist. Originally considered a protozoan, William Ophüls determined that Coccidioides was a fungus and that the lungs were the apparent initial site of infection. During the 1930s, both Gifford and Dickson determined that a self-limited illness, Valley Fever, was caused by the same fungus that caused the often fatal coccidioidal granuloma. Charles Smith, over a period of approximately 2 decades, comprehensively described the clinical and geographic epidemiology of coccidioidomycosis in California. Demosthenes Pappagianis continued this work after Smith's death. In 1957, one year before Marshall Fiese published his masterful monograph on coccidioidomycosis, the use of the first effective agent for the therapy of coccidioidomycosis, amphotericin B, was reported. This was followed by descriptions of its appropriate clinical use by William Winn and by Hans Einstein, among others. The development of the much less toxic azole antifungal agents greatly simplified therapy in many cases, but much of the management of patients with coccidioidomycosis still relies more on art than science. The search for the "Holy Grail" - a vaccine capable of preventing this disease-continues.

Prolonged voriconazole treatment in a patient with chronic lymphocytic leukemia resulting in a litany of chronic overlapping toxicities.

Voriconazole is a triazole antifungal with activity against a number of yeast and mold species including Candida, Aspergillosis, Fusarium, and Coccidioides. Invasive fungal infections are associated with high morbidity and mortality, prolonged treatment courses, and occasionally lifelong suppressive therapy. Voriconazole therapy can result in a number of acute toxicities that clinicians are frequently aware of including hepatotoxicity, visual disturbances, and hallucinations; however, there is limited experience with extended durations of voriconazole therapy. We describe the case of a 62-year-old man who developed Coccidioides meningitis as a result of prolonged neutropenia from treatment for chronic lymphocytic leukemia. He was initially treated with a number of different antifungal agents including voriconazole, liposomal amphotericin B, fluconazole, and itraconazole; however, he developed acute toxicity due to those agents. He was successfully re-challenged with voriconazole, and maintained therapeutic serum concentrations throughout treatment. As a result of prolonged voriconazole exposure of over 14 years, he has suffered a number of toxicities, most significantly including actinic keratosis, squamous cell carcinoma, and skeletal fluorosis. To our knowledge, this is the longest continuous use of voriconazole therapy currently in the literature.

Coccidioidomycosis in selected immunosuppressed hosts.

After contracting coccidioidomycosis, persons with impaired cellular immunity are more likely than healthy persons to have severe infection, disseminated infection, and higher mortality rates. In this brief review, we summarize the clinical manifestations, diagnosis, treatment, and prevention of coccidioidomycosis in persons infected with human immunodeficiency virus (HIV), recipients of solid organ or hematopoietic stem cell transplants, and recipients of biologic response modifiers. Among individuals infected with HIV, a diagnosis of acquired immunodeficiency syndrome (AIDS) and a CD4 T-lymphocyte count <250 cells/µl were associated with more severe coccidioidomycosis, whereas less severe disease occurred among those with undetectable HIV-RNA and higher CD4 T-lymphocyte counts, indicating that controlled HIV viremia and improved cellular immune status are important in limiting disease. For transplant recipients whose immunosuppression typically peaks in the first 3 to 6 months and tapers thereafter, the greatest risk of acute coccidioidomycosis occurs 6 to 12 months after transplantation. Relapses of recent coccidioidomycosis may occur during ongoing immunosuppression when patients are not taking suppressive antifungal medication. Recipients of biologic agents, especially those that impair tumor necrosis factor α (TNF-α), may be at increased risk for poorly controlled coccidioidomycosis; however, the best way to prevent and treat such infections has yet to be defined.