Syndrome of inappropriate antidiuretic hormone release secondary to central nervous system coccidioidomycosis with vasculitis.

A man in his 60s presented to the clinic due to night sweats and weight loss following pneumonia. He was found to have hyponatraemia due to a syndrome of inappropriate antidiuretic hormone (SIADH). CT of the thorax was concerning for pulmonary nodules. He was ultimately diagnosed with pulmonary coccidioidomycosis (CM) and started on fluconazole 400 mg daily with improvement in symptoms. Due to the report of headaches, head MRI was conducted which suggested central nervous system (CNS) involvement. Cerebrospinal fluid analysis was consistent with CNS CM and head magnetic resonance angiography confirmed the presence of CNS vasculitis. Fluconazole dose was increased to 800 mg daily which the patient continued to tolerate and showed improvement. This report depicts a case of SIADH associated with CNS CM with vasculitis and demonstrates the importance of high clinical suspicion for SIADH secondary to CNS CM in the setting of hyponatraemia and headache.

"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.

Non-shunt Management of Communicating Hydrocephalus in an Immunocompetent Host With Disseminated Central Nervous System Coccidioidomycosis.

Disseminated coccidioidomycosis is associated with significant morbidity and mortality. Involvement of the meninges is often fatal if untreated, typically requiring lifelong antifungal therapy and neurosurgical intervention. We present the case of a young male without any known immunocompromising conditions who opted exclusively for medical management of newly diagnosed coccidioidomycosis meningitis with communicating hydrocephalus and discuss the controversy associated with this approach. This case highlights the importance of shared decision-making between patient and clinician, even if the plan diverges from available guidelines. Furthermore, we discuss clinical considerations in approaching the close outpatient monitoring of patients with central nervous system coccidioidomycosis with hydrocephalus.

Fatal septic shock due to disseminated coccidioidomycosis: a case series and review of the literature.

BACKGROUND: Coccidioidomycosis is a fungal infection endemic to the southwestern United States and regions of Latin America. Disseminated disease occurs in < 1% of cases. Septic shock is even rarer, with high mortality despite therapy. We describe two cases of coccidioidal septic shock. Both patients were older men of Filipino ancestry presenting with respiratory failure and vasopressor-dependent shock. Antifungal drugs were initiated after failure to improve with empiric antibiotics; in both, Coccidioides was isolated from respiratory cultures. Despite aggressive care, both patients ultimately died of their infections. We provide a review of the published literature on this topic. CONCLUSIONS: Most of the 33 reported cases of coccidioidal septic shock occurred in men (88%) of non-white race and ethnicity (78%). The overall mortality rate was 76%. All survivors received amphotericin B as part of their treatment. Coccidioidomycosis-related septic shock is a rare disease with poor outcomes; delays in diagnosis and treatment are common. Improved diagnostic testing for coccidioidomycosis could enhance recognition of this disease in the future. Although data are limited, early treatment with amphotericin B in cases of coccidioidal septic shock may reduce mortality.

Asymptomatic Coccidioidal Meningitis Relapse: A Demon in Disguise.

Coccidioides spp is a soil-dwelling, dimorphic fungus that causes coccidioidomycosis. It is endemic to the western hemisphere. Although primarily a respiratory disease, it can also cause a myriad of clinical manifestations, from asymptomatic disease to meningitis. In fact, Coccidioides species is probably the most common etiologic agent of long-term meningitis in California and Arizona. Early diagnosis and treatment are critical to avoid fatal complications. With treatment, the cerebral spinal fluid analysis may return to normal. Relapse of coccidioidal meningitis is usually suspected with recurrence of meningitis symptoms. The patient is a 53-year-old man with a 2-decade history of coccidioidal meningitis who was diagnosed with an asymptomatic relapse of coccidioidal meningitis.

Fatal Disseminated Coccidioidomycosis in Cirrhosis: A Case Series.

PURPOSE: Coccidioidomycosis is endemic to the Southwest United States and Mexico. In this case series we describe 3 cases, occurring in the Southwest United States, of patients with disseminated coccidioidomycosis infection in cirrhosis, all with a miliary pattern present on chest imaging. METHODS: This case series was performed conducting a review of patients' electronic health records and thorough review of the literature for coccidioidomycosis infection in patients with liver disease. RESULTS: Three patients with different etiology of liver disease with Model for End-stage Liver Disease - Sodium (MELD-Na) scores >20 had chest imaging findings indicative of a miliary pattern on presentation. Each patient subsequently had extensive infectious disease workup that showed evidence of disseminated coccidioidomycosis. All 3 patients clinically worsened and eventually died. CONCLUSIONS: This case series highlights the severity of disseminated coccidioidomycosis in patients with cirrhosis in an endemic area, as well as potential early clues such as miliary patterns on chest imaging. A review of the literature found a significant connection among potential mechanisms describing why patients with cirrhosis have such adverse outcomes in the setting of disseminated coccidioidomycosis, including cirrhosis-associated immune dysfunction and genetic defects in immune functioning.

Cerebrovascular Accident Caused by Coccidioides immitis Basilar Meningitis in a Patient with Stroke Risk Factors.

A 57-year-old female with a history of type 2 diabetes mellitus and hypertension presented to the emergency department on multiple occasions with neurologic symptoms due to multiple embolic strokes of unclear etiology. While participating in inpatient rehabilitation, she subsequently developed fever and shaking chills. Infectious disease consultation was obtained, during which the patient reported travel to Mexico two months prior. Further diagnostic testing revealed basilar-predominant leptomeningeal enhancement and serum fungal antibody testing returned positive for Coccidioides immitis. This led to a diagnosis of Coccidioides immitis with secondary vasculitis causing multifocal ischemic stroke. The patient's neurologic function has returned to normal after treatment with fluconazole, and life-long treatment with fluconazole is planned. This case underscores the importance of obtaining a travel history.

Angiolymphoid Hyperplasia with Eosinophilia in a Patient With Coccidioidomycosis.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare nodular mass that has not commonly been reported in the literature in association with coccidioidomycosis (CM). Coccidioidomycosis has other known skin manifestations including erythema nodosum and interstitial granulomatous dermatitis. Pulmonary CM is the most common form of the disease and the most common cause of CM-associated rash. This is an important clinical consideration for patients with ALHE who reside in CM-endemic areas, which notably include the southwestern region of the United States, Mexico, and South America. We report the case of an ALHE lesion that resolved following treatment for CM.

Controversies in the Management of Central Nervous System Coccidioidomycosis.

Central nervous system infection with Coccidioides spp. is fatal if untreated and complications occur even when therapy is directed by experienced clinicians. We convened a panel of clinicians experienced in the management of coccidioidal meningitis to summarize current controversies and provide consensus for the management of this difficult infection.

A Case of Concurrent Disseminated Coccidioidomycosis and Embryonal Carcinoma When Lice and Fleas Coexist.

Coccidioidomycosis (CM) is a fungal infection endemic to the southwestern United States with a wide range of clinical presentations depending on the infected organ systems. Most infections are asymptomatic. Coccidioidomycosis causes a primary pulmonary infection and when symptoms occur, they most often resemble community-acquired pneumonia. One percent of cases disseminate, typically via hematogenous or lymphatic spread. It is in these cases that more severe symptoms may present and potentially overlap with those characteristics of other systemic illnesses. This is a case of CM disseminated to lymph nodes in a 24-year-old man with concomitant metastatic embryonal carcinoma. It is difficult to identify the primary etiology for many components of this patient's presentation, including diffuse lymphadenopathy and multiple pulmonary nodules. Furthermore, the relationship between these 2 concurrent disease processes is not entirely clear. Factors that may contribute include the well-known phenomenon of locus minoris resistentiae (LMR) or potentially a shared immune failure between infectious organisms and malignant cells.

Comparison of Shunt Outcomes for Nonbacterial Infection Hydrocephalus with Common Hydrocephalus Etiologies: A Retrospective Case-Control Study.

BACKGROUND: Shunting is an established treatment for hydrocephalus, yet reports on shunt outcomes for nonbacterial infection (NBI) hydrocephalus are limited. Furthermore, comparison of mechanisms and rates of failure for shunted NBI hydrocephalus versus more typical etiologies remains undetermined. METHODS: Patients who underwent shunting for hydrocephalus at 2 centers (1995-2020) were included. Indications for shunting were grouped as "typical" (congenital, posthemorrhagic, normal pressure hydrocephalus, malignancy-related, trauma, and idiopathic) and NBI hydrocephalus (coccidioidomycosis, cryptococcosis, and neurocysticercosis). Rates of shunt malfunction were compared. RESULTS: There were 261 patients shunted for typical hydrocephalus (48.7% male; age = 50.7 ± 21.7) and 93 patients for NBI hydrocephalus (72.0% male; age = 41.8 ± 13.2). For patients with typical hydrocephalus, 29.5% required ≥1 shunt revision, compared with 64.5% with NBI hydrocephalus (P < 1E-5). Of those with malfunction, NBI shunts required more revision operations (median = 3.0; max = 21) than typical shunts (median = 2.0; max = 6; P < 0.05). The censored median time to shunt failure for NBI hydrocephalus was 26.9 months and was not reached for typical etiologies by 180 months. Multivariate analysis showed shunts for NBI hydrocephalus were significantly more likely to fail (hazard ratio = 2.25; 95% confidence interval = 1.58-3.19). A distal pseudocyst was implicated in 30.0% and 2.6% of shunt failures for NBI and typical hydrocephalus, respectively (P < 1E-5). Sixteen (26.7%) NBI shunt failures required revision to lower-resistance systems compared to 6 (7.8%) typical failures (P < 0.05). CONCLUSIONS: Shunts placed for hydrocephalus secondary to nonbacterial infections are complicated by significantly higher rates of malfunction. These patients are prone to develop distal abdominal pseudocysts and often require revision to low-resistance systems.

A Case of Thyroidal Coccidioidal Infection.

Infection of the thyroid gland with Coccidioides immitis is rare. We report a case with disseminated coccidiomycosis involving thyroid gland as a thyroid nodule. Although historical autopsy studies have indicated that coccidioidal involvement of the thyroid gland can infrequently occur as part of disseminated infection, to our knowledge, only less than 10 other cases have been reported. Optimal treatment duration and dosage of medication are uncertain in literature of this rare involvement of thyroid gland with coccidioidomycosis.

Pulmonary Giant Cavitary Coccidioides With Fungal Ball and Hemoptysis.

Coccidioidomycosis (CM) is a fungal disease that results from inhalation of spores of Coccidioides immitis and C posadasii. If symptomatic, disease primarily manifests as community-acquired pneumonia; however, additional pulmonary manifestations such as pleural effusion, empyema, and cavitation may occur. Diabetic patients have an increased risk of severe and cavitary CM. Cavitary disease may erode vasculature and pulmonary parenchyma leading to further complications. Furthermore, chronic cavities can become colonized as well and develop superimposed infections. This is a case of cavitary CM in uncontrolled diabetic nonadherent to treatment presenting with hemoptysis and mycetoma.

Coccidioidomycosis Resulting in a Prosthetic Joint Infection in an Immunocompetent Patient after a Total Hip Arthroplasty: A Case Report and Review of the Literature.

INTRODUCTION/BACKGROUND: Coccidioidomycosis is a fungal infection that is a rare cause of prosthetic joint infection (PJI) in patients. CASE PRESENTATION: This case report describes an immunocompetent patient who had a right total hip arthroplasty (THA) complicated with Coccidioidomycosis. This patient is the 9th reported case of Coccidioidomycosis, causing a PJI and only the second case to be reported in a THA. Once progressed, it can be difficult to treat, often reoccurring and requiring repeat surgical and prolonged therapy. CONCLUSION: This study discusses the clinical presentation in this patient and reviews the literature on the currently published cases.

Disseminated Coccidioidomycosis as the First Presentation of a C-Terminal NFKB2 Pathogenic Variant: A Case Report and Review of the Literature.

INTRODUCTION: Although most cases of coccidioidomycosis are subclinical or self-limited respiratory disease, 1% lead to extrathoracic dissemination and become fatal, especially in patients with an associated immunodeficiency. Up to 30%-50% of patients with defects in cell-mediated immunity, those with AIDS and recipients of solid-organ transplants, may develop disseminated coccidioidomycosis (DC). Within the primary immunodeficiencies, an uncommon group is caused by C-terminal NFKB2 pathogenic variants. MATERIALS AND METHODS: We performed a literature search of core databases. Written informed consent for the study and for publication was obtained. CASE PRESENTATION: A 7-year-old Mexican girl, eldest of 3 sisters, no relevant family history, and a history of recurrent upper respiratory infections and alopecia totalis was admitted with DC involving pulmonary, soft tissue, skin, bone and joint compromise. The immunodeficiency assessment showed low IgM and NK cells. We found an NFKB2 de novo heterozygous nonsense mutation of c.2611C>T (p.Gln871*). She was treated with liposomal amphotericin B and itraconazole with surgical debridement. The clinical phenotype of this primary immunodeficiency is characterized by antibody deficiency and associated broncho-pulmonary predisposition to infection, but moreover also opportunistic infections and autoimmunity, most recognizable alopecia and adrenocorticotropic hormone-deficiency. After 1 year of her discharge, she continues under surveillance with antifungal therapy with itraconazole and replacement intravenous immunoglobulin until today. CONCLUSION: This is the first case report of DC in a patient with an NFKB2 pathogenic variant and it illustrates the importance of screening for primary immunodeficiencies in patients with disseminated fungal infections.

Coccidioidal Hepatic Abscess in a Patient With Disseminated Coccidioidomycosis: A Case Report.

Coccidioidomycosis is an infection caused by inhalation of arthroconidia of Coccidioides. Forty percent of patients will develop mild and self-limited respiratory infection, and a small fraction of these individuals will develop extrapulmonary disseminated disease. This is the case of a patient with a known history of disseminated coccidioidomycosis, who initially presented for symptoms of persistent pneumonia. On evaluation, the patient was found to have a hepatic abscess for which he underwent percutaneous drainage. Culture grew Coccidioides immitis, and the patient was treated with systemic antifungal. This is a rare case of disseminated coccidioidomycosis in the liver.

Accelerated Progression of Disseminated Coccidioidomycosis Following SARS-CoV-2 Infection: A Case Report.

We describe a patient with subclinical coccidioidomycosis who experienced rapid disease dissemination shortly after SARS-CoV-2 infection, suggesting host immune response dysregulation to coccidioidomycosis by SARS-CoV-2. We hypothesize that disrupted cell-mediated signaling may result after SARS-CoV-2 infection leading to functional exhaustion and CD8+ T-cell senescence with impairment in host cellular response to Coccidioides infection.

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.