Cerebrovascular complications of coccidioidomycosis meningitis: Case report and systematic review.

Coccidioidomycosis exposure is common in the southwest United States and northern Mexico. Dissemination to the meninges is the most severe form of progression. Although ischemic strokes are well-reported in these patients, other cerebrovascular complications of coccidioidomycosis meningitis (CM), as well as their treatment options and outcomes, have not been systematically studied. We present a uniquely severe case of CM with several cerebrovascular complications. We also systematically queried PubMed and EMBASE databases, including articles published before April 2020 reporting human patients with CM-induced cerebrovascular pathology other than ischemic infarcts. Sixteen articles met inclusion criteria, which describe 6 patients with aneurysmal hemorrhage, 10 with non-aneurysmal hemorrhage, one with vasospasm, and one with transient ischemic attacks. CM-associated aneurysms invariably presented with hemorrhage. These were universally fatal until the past decade, when advances in surgical clipping and/or combined surgical and endovascular treatment have improved outcomes. We found that non-aneurysmal intracranial hemorrhages were limited to male patients, involved a diverse set of intracranial vasculature, and had a mortality rate surpassing 80%. Vasospasm was reported once, and was treated with percutaneous transluminal angioplasty. Transient ischemic attacks were reported once, and were successfully treated with fluconazole and dexamethasone. This review suggests that CM can present with a wide array of cerebrovascular complications, including ischemic infarcts, aneurysmogenesis, non-aneurysmal intracranial hemorrhage, vasospasm, and transient ischemic attacks. Mortality has improved over time due to advances in surgical and endovascular treatment modalities. The exception is non-aneurysmal intracranial hemorrhage, which remains associated with high mortality rates and few targeted therapeutic options.

Endemic Fungi Presenting as Community-Acquired Pneumonia: A Review.

In endemic areas, dimorphic fungal infections due to Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides posadasii/immitis account for up to 30% of cases of community-acquired pneumonia. Because respiratory manifestations are often indistinguishable from common bacterial causes of pneumonia, the diagnosis of pulmonary histoplasmosis, blastomycosis, and coccidioidomycosis is often delayed and associated with antibiotics overuse. In addition to being highly endemic to certain regions of North America, dimorphic fungi have global significance due to established areas of endemicity in all six inhabited continents, an increasingly interconnected world of travelers and transported goods, and a changing epidemiology as a result of global heating and anthropomorphic land utilization. In this review, we discuss the epidemiology, pathogenesis, clinical presentation, diagnostic modalities, and treatment strategies for histoplasmosis, blastomycosis, and coccidioidomycosis.

Coccidioidomycosis (Valley Fever) in Primary Care.

Primary pulmonary coccidioidomycosis (valley fever) is caused by inhaling airborne spores of the fungus Coccidioides immitis or Coccidioides posadasii. Residing in or traveling to areas endemic for Coccidioides is required for the diagnosis; no person-to-person or zoonotic contagion occurs. The incidence of coccidioidomycosis is increasing in endemic areas, and it has been identified as the cause of as many as 17% to 29% of all cases of community-acquired pneumonia in some regions. Obtaining a travel history is recommended when evaluating patients with community-acquired pneumonia. Diagnosis usually relies on enzyme immunoassay with immunodiffusion confirmation, but these tests may not be positive for one to three weeks after disease onset. Antifungal agents are not recommended for treatment unless the patient is at risk of or shows signs of complicated or disseminated infection. When antifungals are used, fluconazole and itraconazole are most commonly recommended, except during pregnancy. Treatment may continue for as long as three to 12 months, although lifetime treatment is indicated for patients with coccidioidal meningitis. Monitoring of complement fixation titers and chest radiography is recommended until patients stabilize and symptoms resolve. In patients who are treated with antifungals, complement fixation titers should be followed for at least two years.

Charles Edward Smith: Coccidioidomycologist and public health leader.

Although Charles Edward Smith did not discover coccidioidomycosis, he defined the disease through his infatigueable studies of the epidemiology, clinical findings, and immunology of this infection. He became its preeminent authority. He also had an important role in the development of public health, and for the last 16 years of his life he was the Dean of the School of Public Health at the University of California at Berkeley, where he was a revered and energetic leader.

Clinical features of cats diagnosed with coccidioidomycosis in Arizona, 2004-2018.

OBJECTIVES: The goal of this study was to describe the clinical presentation, diagnosis and treatment of coccidioidomycosis in cats residing in a region endemic for Coccidioides species. METHODS: A retrospective review of records was performed at both primary and tertiary care veterinary practices in Tucson and Phoenix, Arizona, USA. Data collected included signalment, clinical signs, physical examination findings, diagnostic test results, treatment and outcome. RESULTS: Fifty-one feline cases were identified from six veterinary hospitals. Cats presented with clinical signs and laboratory abnormalities similar to what has been seen in dogs, including respiratory illness (n = 20/51), neutrophilia (n = 24/31), monocytosis (n = 17/31) and hyperglobulinemia (n = 16/30). However, cats at diagnosis were typically significantly ill, with 31/51 having disseminated infection, most commonly to the skin (n = 22). Additionally, 43/44 cats that had serum antibody tests performed were positive, and median titer at diagnosis was 1:32 (range 1:4 to ⩾1:256). Serum antibody titers were significantly reduced (P ⩽0.001) in cats that responded to treatment compared with cats that did not clinically improve. Forty of 46 cats that were treated with oral fluconazole responded and did not require additional therapy. Fourteen cats developed recurrent disease and all but one had antifungal therapy successfully reinstituted. CONCLUSIONS AND RELEVANCE: Coccidioidomycosis is a disease of concern for cats residing in the regions endemic for Coccidioides species. Disease is most often disseminated at the time of diagnosis, possibly due to delays in presentation for care and recognition of the infection. Suspicion of disease, serum chemistries, blood cell counts, presence of antibody and imaging aid in the diagnosis of coccidioidomycosis in cats. Serum antibody reduction during treatment frequently correlated with an adequate response to medication. Consideration of coccidioidomycosis as a cause of illness will lead to earlier diagnosis and potentially better treatment outcomes in cats.

[Clinical Features of Coccidioidomycosis:Analysis of 33 Chinese Cases].

Objective To summarize the characteristics of Chinese coccidioidomycosis cases, improve the diagnosis and treatment of this disease and prevent misdiagnosis as well as therapeutic error.Methods Search in databases including Medline,Wanfang,and CNKI using "Coccidioidomycosis" and "China" as index words yielded 23 articles that reported a total of 32 Chinese coccidioidomycosis cases.In addition,one patient with disseminated coccidioidomycos was treated in our center in April 2016.The demographic data,site of infection,clinical manifestations,past medical history,exposure history,imaging and laboratory findings,and pathological features of these 33 patients were analyzed.Results Among these 33 patients,7(21.2%)had visited an epidemic area and 6(18.2%)were immunocompromised.The disease involved the respiratory system,skin,bone,central nervous system,cornea,and stomach in 24,6,3,2,1,and 1 patients,respectively.Eight patients (24.2%) had multiple system involvement,and three of them died.The imaging findings included pulmonary nodules(n=14),mediastinal lymphadenopathy(n=5),solid shadow(n=4),cavity(n=4),pleural effusion(n=3),multiple plaques(n=2)and masses(n=2).Coccidiolys cysts were detected in the affected tissues(n=28)or in pus,exudate or pleural smear(n=3);in addition,coccidioides mycelium and spores were found in the sputum,pus,and tissue cultures in 4 cases,among whom only 2 cases were confirmed by serological examination.The treatments included triazoles(n=20),systemic or local administration of amphotericin B(n=13),surgical resection of the lesion(n=8),and intravenous gamma globulin(n=1).Five patients died,among whom three had underlying diseases that caused immunosuppression and one was an infant.The prognoses were relatively good in the remaining patients.Conclusions Early diagnosis and proper treatment can achieve good prognosis in coccidioidomycosis patients.Multi-system involvement and immunosuppression are risk factors for poor prognosis of coccidioidomycosis.For these patients,adequate and full-course medication may prevent rapid disease progression.

Early Events in Coccidioidomycosis.

Since its description nearly 130 years ago, hundreds of studies have deepened our understanding of coccidioidomycosis, also known as valley fever (VF), and provided useful diagnostic tests and treatments for the disease caused by the dimorphic fungi Coccidioides spp. In general, most of the literature has addressed well-established infections and has described patients who have experienced major complications. In contrast, little attention has been given to the earliest consequences of the pathogen-host interaction and its implications for disease manifestation, progression, and resolution. The purpose of this review is to highlight published studies on early coccidioidomycosis, identify gaps in our knowledge, and suggest new or former research areas that might be or remain fertile ground for insight into the early stages of this invasive fungal disease.

A 37-Year-Old Man With Pleuritic Chest Pain.

CASE PRESENTATION: A 37-year-old man with poorly controlled type 2 diabetes presented with severe right-sided pleuritic chest pain, respiratory splinting, and cough. Two weeks earlier, he had been evaluated at an urgent care for cough and was prescribed a 5-day course of azithromycin for bronchitis. He then presented to our ED reporting mild, right-sided pleuritic chest pain. Vital signs were normal, and his chest radiograph showed a trace right pleural effusion (Fig 1A). He was discharged with naproxen for pleurisy. Three days later, he returned, reporting a dramatic increase in the severity of his pleuritic chest pain and a cough that had become productive of yellow-brown sputum. He denied fever, but endorsed chills and night sweats. His medications included atorvastatin, lisinopril, metformin, and saxagliptin. His parents were from Guam, although he was born and raised in San Diego, CA. He was employed as a social worker and denied any history of cigarette smoking, alcohol, or drug use.

The role of extracorporeal membrane oxygenation in severe pulmonary coccidioidomycosis.

BACKGROUND: Severe coccidioidal pneumonia with acute respiratory distress syndrome (ARDS) is associated with high mortality. Extracorporeal membrane oxygenation (ECMO) has been applied successfully to other severe fungal pneumonia associated with ARDS. We review our experience with the use of ECMO in severe coccidioidal ARDS. OBJECTIVES: To review indications and outcome of ECMO in severe pulmonary coccidioidomycosis. METHODS: Three cases of severe ARDS caused by coccidioidomycosis are presented. All were managed with ECMO. Clinical course, complications, antifungal therapy and outcome are reviewed. RESULTS: Three cases of severe coccidioidal ARDS survived after treatment with ECMO. Common complications included bacterial pneumonia, encephalopathy and critical illness myopathy. They received liposomal amphotericin during ECMO, and transitioned to azole therapy. All required prolonged hospitalization and rehabilitation. CONCLUSIONS: ECMO was life-saving in cases of coccidioidal ARDS. Common complications included pneumonia, encephalopathy and critical illness myopathy. All cases were successfully managed with liposomal amphotericin followed by azole therapy. They required prolonged hospitalization and rehabilitation.

Coccidioidomycosis, immunoglobulin deficiency: safety challenges with CAR T cells therapy for relapsed lymphoma.

Treatment of patients with relapsed or refractory lymphoma may require allogenic hematopoietic stem cell transplant (HSCT), but treatment of post-transplant relapse disease remains very challenging. Donor lymphocyte infusion and blinatumomab have been used with limited success for the treatment of relapse. Initial data on donor-derived CAR T cells has shown this modality to be safe and highly effective in various hematological malignancies. We present a case of a patient with highly refractory, transformed follicular lymphoma who failed both autologous and allogenic HSCT. Patient achieved long-lasting complete remission with the use of donor origin CD19 CAR T-cell therapy, without any evidence of graft-versus-host disease flare. Our patient later developed disseminated coccidioidomycosis and persistent hypogammaglobulinemia. Immunotherapy using CD19 CAR T cells can be a highly effective salvage modality, especially in cases of focal lymphoma relapse. Long-term immunosuppression secondary to B cell lymphopenia, hypogammaglobulinemia, immunoglobulin subclass deficiency, fungal infections and other infectious complications need to be monitored and promptly treated as indicated.

A 62-Year-Old Woman With Wheezing, Respiratory Failure, and an Abnormal CT Scan.

CASE PRESENTATION: A previously healthy 62-year-old woman was transferred to the ICU from the medical ward with acute bronchospastic respiratory failure requiring intubation and mechanical ventilation. Four weeks before, the patient was vacationing in Arizona and acquired a mildly productive cough as well as mild dyspnea. She presented to an urgent care facility and was diagnosed with community-acquired pneumonia. She received a 5-day course of azithromycin, with partial improvement of her symptoms. The patient returned home 1 week prior to admission, reporting worsening dyspnea, chest pressure, cough, and fever. The patient was admitted to the medical ward, and treatment for unresolved pneumonia was begun with levofloxacin, an inhaled short-acting beta agonist, and oral prednisone. Despite this treatment, the patient experienced severe respiratory distress with audible wheezing as well as increased work of breathing. She was intubated for acute hypoxemic respiratory failure and transferred to the ICU.

Favorable Outcome in Coccidioides Endophthalmitis-A Combined Medical and Surgical Treatment Approach.

PURPOSE: To describe a case of Coccidioides endophthalmitis that resulted in a favorable visual outcome after a combined medical and surgical approach. METHODS: A 33-year-old previously healthy woman was referred for evaluation of dyspnea and left-sided vision loss, which began 3 months before, after a trip to Nevada. She was found to have a pulmonary cavitary lesion and fluffy white material in the anterior chamber. An aqueous and vitreous paracentesis grew Coccidioides species. She was managed medically with a total of 7 weekly intravitreal injections of amphotericin B and intravenous liposomal amphotericin B followed by transition to oral posaconazole. Seven months after presentation, to ensure ocular sterilization and to clear the visual axis, she underwent temporary keratoprosthesis implantation, anterior segment reconstruction, removal of a cyclitic membrane and the crystalline lens, pars plana vitrectomy, placement of a pars plana Ahmed drainage device, and penetrating keratoplasty. RESULTS: After surgical intervention and with maintenance posaconazole therapy, the patient had resolution of her dyspnea and improved uncorrected (aphakic) vision with a clear corneal graft, quiet anterior chamber, and normal optic nerve and retina. CONCLUSIONS: A combined medical and surgical approach resulted in a favorable visual outcome and avoided the need for enucleation.

Diagnosis and Management of Coccidioidomycosis.

Coccidioidomycosis is a leading cause of community-acquired pneumonia within its traditional endemic zone in the Southwestern United States and portions of Mexico and Central and South America. Its incidence has increased dramatically within the endemic region; its presence outside of the region, facilitated by a mobile society, is also now substantial. Although only a fraction of the incident disease progresses beyond subclinical illness, this proportion is large in absolute terms and causes substantial disease burden. Diagnosis often depends on serologic interpretation. Treatment has been revolutionized by azole therapy. Controversy remains regarding the decision to treat in less severe disease.

Spinal Coccidioidomycosis: A Current Review of Diagnosis and Management.

OBJECTIVE: Coccidioidomycosis is an invasive fungal disease that may present with extrathoracic dissemination. Patients with spinal coccidioidomycosis require unique medical and surgical management. We review the risk factors and clinical presentations, discuss the indications for surgical intervention, and evaluate outcomes and complications after medical and surgical management. METHODS: A review of the English-language literature was performed. Eighteen articles included the management of 140 patients with spinal coccidioidomycosis. RESULTS: For the 140 patients, risk factors included male sex (95%), African American ethnicity (52%), and a recent visit to endemic areas (16%). The most frequent clinical presentation was pain (n = 80, 57%), followed by neurologic compression (52%). One-third of patients had concurrent pulmonary disease. The sensitivity of culture and histology for coccidioidomycosis was 80% and 90%, respectively. Complement fixation titers >1:128 suggest extensive or refractory vertebral infection. The most commonly affected spinal segments were the thoracic and lumbar spine (69%); an additional 40 patients (29%) had epidural and paravertebral abscesses. All patients received therapy with azoles (60%) and/or amphotericin B (43%). Surgical and medical management were used conjunctively to treat 110 patients (79%), with debridement (95% [105/110]) and fusion (64% [70/110]) being the most common surgical procedures. Clinical outcome improved/remained unchanged in 83 patients (59%) and worsened in 4 patients (3%). The mortality was 7%. Infection recurrence and disease progression were the most frequent complications. CONCLUSIONS: Emphasis should be placed on continuous and lifelong appropriate azole therapy. Spinal instability and neurologic compromise are surgical indications for decompression and fusion.

Integrative Medicine Preferences Among Coccidioidomycosis (Valley Fever) Patients.

OBJECTIVES: To understand the extent and modalities of integrative medicine strategies that patients with coccidioidomycosis (valley fever) have incorporated into their treatment regimens. DESIGN: A direct patient survey was distributed, with 100 unique responses, at a single infectious diseases clinic at an academic medical center in Arizona. Eligible patients, defined as those with confirmed coccidioidomycosis or currently under evaluation, were polled on their personal use of 36 integrative medicine modalities. Patients were also asked to indicate their level of fatigue on a 10-point scale in an attempt to correlate levels of fatigue to use of specific integrative medicine modalities. RESULTS: Of the patients surveyed, 64% had used at least one integrative medicine modality, and 53% used two or more, along with conventional medical therapy. The top three modalities were nutrition (39%), massage (27%), and breathing exercises (26%). The mean reported fatigue level was 4.7 on a 10-point scale, with a standard deviation of 3.0. There was no statistically significant association between use of a specific modality and reported level of fatigue. CONCLUSIONS: Nearly two thirds of patients (64%) surveyed had used at least one integrative medicine modality throughout the course of their therapy. Clinicians are probably unaware of the extent to which many patients, including this population, have embraced integrative medicine. Awareness of patients' goal and preferences is valuable in shared clinical decision making.