Case report: Rapidly progressive neurocognitive disorder with a fatal outcome in a patient with PU.1 mutated agammaglobulinemia.

Introduction: PU.1-mutated agammaglobulinemia (PU.MA) represents a recently described autosomal-dominant form of agammaglobulinemia caused by mutation of the SPI1 gene. This gene codes for PU.1 pioneer transcription factor important for the maturation of monocytes, B lymphocytes, and conventional dendritic cells. Only six cases with PU.MA, presenting with chronic sinopulmonary and systemic enteroviral infections, have been previously described. Accumulating literature evidence suggests a possible relationship between SPI1 mutation, microglial phagocytic dysfunction, and the development of Alzheimer's disease (AD). Case description: We present a Caucasian female patient born from a non-consanguineous marriage, who was diagnosed with agammaglobulinemia at the age of 15 years when the immunoglobulin replacement therapy was started. During the following seventeen years, she was treated for recurrent respiratory and intestinal infections. At the age of 33 years, the diagnosis of celiac-like disease was established. Five years later progressive cognitive deterioration, unstable gait, speech disturbances, and behavioral changes developed. Comprehensive microbiological investigations were negative, excluding possible infective etiology. Brain MRI, 18FDG-PET-CT, and neuropsychological testing were suggestive for a diagnosis of a frontal variant of AD. Clinical exome sequencing revealed the presence of a novel frameshift heterozygous variant c.441dup in exon 4 of the SPI1 gene. Despite intensive therapy, the patient passed away a few months after the onset of the first neurological symptoms. Conclusion: We describe the first case of PU.MA patient presenting with a rapidly progressive neurocognitive deterioration. The possible role of microglial dysfunction in patients with SPI1 mutation could explain their susceptibility to neurodegenerative diseases thus highlighting the importance of genetic testing in patients with inborn errors of immunity. Since PU.MA represents a newly described form of agammaglobulinemia, our case expands the spectrum of manifestations associated with SPI1 mutation.

The Role of Echocardiography and Cardiac Computed Tomography in Diagnosis of Infective Endocarditis.

BACKGROUND: Infective endocarditis (IE) is a rare disease with a high mortality rate and rising incidence, requiring timely and precise diagnosis in order to choose appropriate therapy. Imaging of morphologic lesions is an integrative part of diagnosis. Artifacts and the patient's habitus make echocardiography difficult to visualize advanced-form IE. Cardiac computed tomography (CCT) constantly shows an additive diagnostic value due to high resolution of cardiac anatomy. Conjecturally, joint application of both diagnostic tests improves overall sensitivity and specificity in diagnosing IE. METHODS: Patients with definite IE underwent transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), and CCT. We analyzed valvular and paravalvular IE lesions in all three imaging methods and compared them to surgical or autopsy findings. We calculated sensitivity, specificity, diagnostic accuracy, and positive and negative predictive value of both imaging tests individually and jointly used. RESULTS: We examined 78 patients, male to female ratio 2:1, mean age 52.29 ± 16.62. We analyzed 85 valves, 70 native valves, 13 prosthetic valves, and 2 corrected valves due to Ozaki procedure, along with a central shunt and 4 pacemaker leads. As a single test, the sensitivity and specificity of CCT, TTE, and TEE for valvular lesions were 91.6/20%, 65.5/57.9%, and 60/84%, and paravalvular lesions were 100/0%, 46/10.5%, and 14.7/100%. When combined together, sensitivity and specificity for valvular lesions rose to 96.6/0% and paravalvular lesions to 100/0%. We also analyzed the diagnostic performance for each test in single and mutual application, per specific IE lesion. CONCLUSION: In the individual application, CCT in comparison to TTE and TEE shows better diagnostic performance in detection of valvular and paravalvular lesions. In joint application, there is a statistically significant difference in performance compared to their single use, especially in prosthetic valves and invasive forms of IE native valves.

Successful pregnancies in a patient with Takayasu arteritis and antiphospholipid syndrome, maintained on infliximab corticosteroid-free regimen: case-based review.

Takayasu arteritis (TA) is a large vessel vasculitis affecting predominantly females below the age of 40. Patients with TA seem to be at increased risk for adverse pregnancy outcomes, resulting in mother or child complications. Although few studies analyzed the presence of antiphospholipid antibodies (APLA) in TA patients, an association between antiphospholipid syndrome (APS) and TA is rarely reported in the literature, mainly in the form of case reports. In fact, very few data regarding pregnancy outcomes in patients with TA and APS are available. An active form of Crohn's disease (CD) might be another risk factor strongly affecting the fertility rate. Here, we would like to present a 33-year-old woman with TA, double-positive APS and Crohn's disease (CD). The report is followed by the literature review of the association of APLA and/or APS with TA, focusing on analyzing the pregnancy outcomes. To our knowledge, this is the first case describing two successful, naturally occurring pregnancies, in a patient suffering from TA, APS and CD, and maintained on infliximab, azathioprine, and a corticosteroid-free regimen.

Large-Vessel Giant Cell Arteritis following COVID-19-What Can HLA Typing Reveal?

Giant cell arteritis (GCA) is an immune-mediated vasculitis that affects large arteries. It has been hypothesized that viruses may trigger inflammation within the vessel walls. Genetic studies on human leukocyte antigens (HLAs) have previously reported HLA-DRB1*04 as a susceptible allele for GCA and HLA-DRB1*15 as a protective allele for GCA. Here, we discuss the clinical presentation, laboratory findings, HLA class I and class II analysis results, and management of patients with extracranial large-vessel (LV) GCA, detected at least six weeks after recovery from COVID-19. This case series encompassed three patients with LV-GCA (two males and a female with an age range of 63-69 years) whose leading clinical presentation included the presence of constitutional symptoms and significantly elevated inflammatory markers. The diagnosis of LV-GCA was confirmed by CT angiography and FDG-PET/CT, revealing inflammation in the large vessels. All were treated with corticosteroids, while two received adjunctive therapy. By analyzing HLA profiles, we found no presence of the susceptible HLA-DRB1*04 allele, while the HLA-DRB1*15 allele was detected in two patients. In conclusion, LV-GCA may be triggered by COVID-19. We highlight the importance of the early identification of LV-GCA following SARS-CoV-2 infection, which may be delayed due to the overlapping clinical features of GCA and COVID-19. The prompt initiation of therapy is necessary in order to avoid severe vascular complications. Future studies will better define the role of specific HLA alleles in patients who developed GCA following COVID-19.

The role of imaging in infective endocarditis.

Infective endocarditis (IE) poses a large diagnostic and therapeutical challenge. An early diagnosis is necessary for a positive outcome. Echocardiography is initial diagnostic method when there is a possibility of IE presence. TTE and TEE are useful in detection, accurate localisation and estimation of vegetation size, and also in detection of paravalvular spreading of infection. In certain situations, there is a need for usage of complementary methods like CCT and nuclear techniques. This article will outline advantages and limitations of certain diagnostic methods in diagnosis of IE.

Impact of the bronchopulmonary sequestration on endobronchial tuberculosis: the case report and the review of literature.

INTRODUCTION: We describe the rare case of endobronchial tuberculosis (EBTB) and chronic pulmonary atelectasis with mediastinal distortion. Finding of the concomitant venous anomaly of inferior vena cava revealed the diagnosis of bronchopulmonary sequestration. CASE REPORT: A 22-year-old Caucasian woman presented with a history of chronic cough, initially treated as bronchial asthma for a year. Chest X-ray showed fibrocaseous cavernous tuberculosis on the right lung. Acid Fast Bacilli (AFB) were found in sputum samples. Patient was treated for 6 months with usual antituberculous regiment. Control chest X-ray showed subatelectasis of the upper right lobe. Six months later the first thorax computed tomography (CT) showed complete atelectasis of the right lung. Patient was admitted to the hospital again after 6 years due to the persistent fever and cough. Endoscopic finding and histopathological analysis confirmed EBTB. Thoracic CT scan revealed duplication of inferior vena cava which led to profound vascular analysis and aberrant arterial vascularization of aortic origin that contributed to the diagnosis of bronchopulmonary sequestrations. Antituberculous treatment was initiated (streptomycin, isoniazid, rifampicin, ethambutol and pyrazinamide) and lasted for 8 months. After 8 months a follow-up fiberoptic bronchoscopy showed the progression of endoscopic finding with 60-70% tracheal stenosis. Histopathological finding of the mid-trachea showed non-specific granulations. During 7 years of follow-up repeated bronchoscopy and thoracic CT scans were unchanged and patient was well-shaped. CONCLUSIONS: The clinician should consider bronchopulmonary sequestration in the cases of recurrent EBTB.