This article describes the background, clinical presentation, diagnosis, and treatment of selected etiologies of subacute and chronic meningitis. Key diagnostic considerations when evaluating a patient presenting with chronic inflammation of the CNS are discussed, and several specific infectious, neoplastic, and autoimmune etiologies are reviewed in detail.With recent advancement in serologic and CSF diagnostic testing, specific infectious, neoplastic, or autoimmune etiologies of chronic meningitis can be identified. Eliminating previous diagnostic uncertainty of chronic inflammation in the CNS has led to rapid and specific treatment regimens that ultimately improve patient outcomes. Recent advances in imaging have also aided clinicians in both their diagnostic approach and the detection of inflammatory complications such as hydrocephalus, hemorrhage, and ischemic stroke.Meningitis is defined as inflammation involving the meninges of the brain and spinal cord. Meningitis can be categorized as acute, subacute, or chronic based on duration of inflammation. This article focuses on the most common causes of subacute and chronic meningitis. Chronic meningitis is commonly defined as inflammation evolving during weeks to months without resolution of CSF abnormalities. Determining the time course of meningitis is important for creating a differential diagnosis. Most organisms causing acute meningitis rarely persist more than a few weeks. Although numerous etiologies of subacute and chronic meningitis have been identified, this article focuses on the most common etiologies: (1) infectious, (2) autoimmune, and (3) neoplastic.

Blastomycosis is a fungal disease that is endemic in parts of North America. It is very rare in China and also commonly misdiagnosed, often as cancer or other infectious diseases. The clinical profile of a case of disseminated blastomycosis with pulmonary changes and skin ulcers was described. He had been misdiagnosed with tuberculosis, after adequate therapy with a lipid formulation of amphotericin B, followed by itraconazole, the lung and skin lesions improved. Then the five cases reported in China and literatures were reviewed. The aim of this report was to improve the knowledge regarding blastomycosis for physicians in China to avoid delaying adequate therapy.

Blastomyces dermatitidis is acquired in almost all cases via inhalation, and pulmonary disease is the most frequent clinical manifestation of blastomycosis. Pulmonary disease can range from asymptomatic infection to rapidly severe and fatal disease. Most cases will present as pneumonia, either acute or chronic, or as a lung mass. In rare cases pulmonary blastomycosis is associated with the acute respiratory distress syndrome. Blastomycosis can present as isolated pulmonary disease or along with coexisting extrapulmonary disease that usually will involve the skin, bony structures, genitourinary tract, or central nervous system. Diagnosis is largely based on isolation of the organism via culture or visualization of the organism in clinical specimens. Detection of urinary Blastomyces antigen is a recent addition to diagnostic options. Itraconazole is the drug of choice for most forms of the disease; amphotericin B is reserved for the more severe forms. Newer azoles such as voriconazole and posaconazole have a limited role in the treatment of pulmonary blastomycosis.

The lipid formulation of amphotericin B is the initial drug of choice for central nervous system blastomycosis, but it is costly and associated with significant toxicity. This case report details a patient with primary pulmonary blastomycosis with dissemination to the skin, one joint, and the brainstem that was successfully treated solely with high-dose fluconazole.

Intraoperative consultation via frozen section is an important part of modern day surgical pathology. Recognizing fungi in tissues on frozen and permanent sections is not always a simple task, and correctly identifying the agent can be a significant challenge, even for experienced microscopists. We present a case of a 17-year-old boy with chronic osteomyelitis involving the right proximal ulna. During an irrigation and debridement operation, a frozen section was sent to surgical pathology for evaluation. A limited patient history coupled with sparse organisms present in the frozen section led to the diagnosis of fungal osteomyelitis, favor Coccidioides . Follow-up permanent sections with special staining and successful fungal culture clarified the causal agent to be Blastomyces dermatitidis . The role of frozen sections is not to perfectly speciate the fungal pathogen but to describe the morphology and infectious process and provide a differential diagnosis of the candidate fungi. The importance of intraoperative culture in infectious cases cannot be understated, and it is the responsibility of pathologists to inform surgeons that tissue is needed for culture. A brief overview of Blastomyces , including histopathologic features and key microscopic differences from Coccidioides and Cryptococcus , is discussed.

Blastomycosis is caused by a dimorphic fungus that can be difficult to diagnose in certain situations. The disease is sometimes serious and can be deadly. Diagnosis by fungal serology and urinary antigens is not easy to establish and unreliable. Culture is also time-consuming and is not easy to perform. Thus, documentation of such an organism on cytology offers a quick and cost-effective alternative. This report describes for the first time identification of the 'negative image' of Blastomyces budding yeast.A 79-year-old man presented with a left lung nodule associated with mediastinal and hilar lymphadenopathy. Fine needle aspiration was performed, and a 'negative image' of a yeast with wide base budding was noted on Diff-Quik (DQ)-stained smears. Blastomyces species were confirmed with periodic acid-Schiff fungal stain. Additionally, the fungal capsule contained focally polarizable material on Congo red stain and lacked mucin with mucicarmine stain.Blastomyces yeast forms can be easily identified with DQ staining by their 'negative image'. This feature can be utilized as a quick and cost-effective cytological characteristic to further triage these specimens for confirmation. The information can be of great value to clinicians in making appropriate clinical decisions.

Pulmonary blastomycosis is an uncommon but serious fungal infection endemic in Wisconsin. Clinician awareness of the protean presentations of this disease may reduce diagnostic delay. This study addressed the diagnostic accuracy of physicians responding to case vignettes of pulmonary blastomycosis and the primary care differential diagnosis of this disease.Eight pulmonary blastomycosis cases were developed from case files. From these, 2 vignettes were randomly selected and mailed to primary care physicians in the Wisconsin Network for Health Research. Respondents were asked to list the 3 most likely diagnoses for each case.Respondents listed Blastomycosis as the most likely diagnosis for 37/227 (16%) case vignettes, and 1 of the 3 most likely diagnoses for 43/227 (19%). When vignettes included patient activity in counties with an annual incidence rate of blastomycosis greater than 2/100,000, compared to counties with lower incidence rates, diagnosis was more accurate (28/61 [46%] vs 15/166 [9%]; P<0.001). Physicians with practice locations in counties with annual blastomycosis incidence rates >2/100,000 listed blastomycosis more commonly than physicians from other counties (16/36 [44%] vs 27/177 [15%]; P<0.001). This difference in accurate diagnosis remained significant in a multivariate model of practice demographics. Based on responses to the vignettes, pneumonia, cancer, non-infectious pulmonary disease, and tuberculosis emerged as the most-frequently noted diagnosis in the differential diagnosis of blastomycosis.Blastomycosis was not listed as 1of 3 primary diagnoses in a majority of cases when Wisconsin primary care physicians considered case vignettes of actual pulmonary blastomycosis cases. Diagnosis was more accurate if the patient vignette listed exposure to a higher incidence county, or if the physician practiced in a higher incidence county. In Wisconsin, failure to include blastomycosis in the differential diagnoses of illnesses associated with a wide variety of pulmonary symptoms suspected to represent infectious or non-infectious pulmonary, cardiac, or neoplastic disease, regardless of geographic exposure, could result in excess morbidity or mortality.

Histologic examination and microbiologic cultures are the gold standards for the diagnosis of infectious granulomatous lung diseases. Although biopsies require invasive procedures, they often yield information that cannot be obtained by other methods. The aims of this article are to outline the major infections that cause granulomatous inflammation in the lung and to familiarize clinicians with the utility of histologic examination in their diagnosis.The histopathologic features of acute pulmonary histoplasmosis and granulomatous Pneumocystis pneumonia have been described in detail, the relative contributions of histology and microbiologic cultures in the diagnosis of blastomycosis have been delineated, and Cryptococcus gattii has emerged as a significant cause of granulomatous pulmonary nodules.The major infectious causes of granulomatous lung disease are mycobacteria and fungi. Histologic examination is particularly important in the diagnosis of pulmonary granulomatous infections when clinical, radiologic and serologic findings are nonspecific. Histology and microbiology play complementary but distinct roles in diagnosis. For organisms that grow slowly in cultures, histology has the additional advantage of being able to provide a rapid diagnosis.

Blastomyces dermatitidis, a thermally dimorphic fungus endemic to areas of North America, causes a granulomatous infection which may affect any organ system. Since limited clinical data exist about pediatric blastomycosis, we conducted a retrospective review of medical records of pediatric patients with a laboratory-confirmed diagnosis of blastomycosis treated during a 30-year period at a tertiary care center. Thirty-four pediatric patients with blastomycosis were identified (20 [59%] male), with a mean age at diagnosis of 10 ± 5 years. Two patients were immunocompromised. Pulmonary disease was noted in 27 (79%) patients, and extrapulmonary disease was found in 13 (38%) patients (concurrent pulmonary and extrapulmonary disease, six patients), including five cases of central nervous system (CNS) disease. Delay in diagnosis was greater with extrapulmonary or central nervous system infections as compared with pulmonary blastomycosis. All patients received antifungal chemotherapy, with 19 (56%) patients receiving amphotericin B as initial therapy for 27.5 ± 17 days. Five patients required treatment in the intensive care unit. One patient died of non-Hodgkins lymphoma. Blastomycosis may occur in healthy children, including very young infants. Due to the frequency of extra-pulmonary disease, diagnosis may be difficult and frequently delayed, especially in cases of CNS infection.