Manish Butte

Meningococcal pneumonia: a review.

Pneumonia (Nathan). 2019;11:3

Authors: Feldman C, Anderson R

Abstract
Background: Although Neisseria meningitidis is one of the major causes of meningitis, meningococcal pneumonia is the most common non-neurological organ disease caused by this pathogen.
Methods: We conducted a review of the literature to describe the risk factors, pathogenesis, clinical features, diagnosis, treatment and prevention of meningococcal pneumonia.
Results: Meningococcal pneumonia was first described in 1907 and during the 1918-1919 influenza pandemic large numbers of cases of meningococcal pneumonia occurred in patients following the initial viral infection. A number of publications, mainly case series or case reports, has subsequently appeared in the literature. Meningococcal pneumonia occurs mainly with serogroups Y, W-135 and B. Risk factors for meningococcal pneumonia have not been well characterised, but appear to include older age, smoking, people living in close contact (e.g. military recruits and students at university), preceding viral and bacterial infections, haematological malignancies, chronic respiratory conditions and various other non-communicable and primary and secondary immunodeficiency diseases. Primary meningococcal pneumonia occurs in 5-10% of patients with meningococcal infection and is indistinguishable clinically from pneumonia caused by other common pathogens. Fever, chills and pleuritic chest pain are the most common symptoms, occurring in > 50% of cases. Productive sputum and dyspnoea are less common. Diagnosis of meningococcal pneumonia may be made by the isolation of the organism in sputum, blood, or normally sterile site cultures, but is likely to underestimate the frequency of meningococcal pneumonia. If validated, PCR-based techniques may be of value for diagnosis in the future. While penicillin was the treatment of choice for meningococcal infection, including pneumonia, prior to 1991, a third generation cephalosporin has been more commonly used thereafter, because of concerns of penicillin resistance. Chemoprophylaxis, using one of a number of antibiotics, has been recommended for close contacts of patients with meningococcal meningitis, and similar benefits may be seen in contacts of patients with meningococcal pneumonia. Effective vaccines are available for the prevention of infection with certain meningococcal serogroups, but this field is still evolving.
Conclusion: Meningococcal pneumonia occurs fairly frequently and should be considered as a possible cause of pneumonia, particularly in patients with specific risk factors.

PMID: 31463180 [PubMed]

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Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network.

Front Immunol. 2019;10:1908

Authors: Cirillo E, Cancrini C, Azzari C, Martino S, Martire B, Pession A, Tommasini A, Naviglio S, Finocchi A, Consolini R, Pierani P, D’Alba I, Putti MC, Marzollo A, Giardino G, Prencipe R, Esposito F, Grasso F, Scarselli A, Di Matteo G, Attardi E, Ricci S, Montin D, Specchia F, Barzaghi F, Cicalese MP, Quaremba G, Lougaris V, Giliani S, Locatelli F, Rossi P, Aiuti A, Badolato R, Plebani A, Pignata C

Abstract
Severe combined immunodeficiencies (SCIDs) are a group of inborn errors of the immune system, usually associated with severe or life-threatening infections. Due to the variability of clinical phenotypes, the diagnostic complexity and the heterogeneity of the genetic basis, they are often difficult to recognize, leading to a significant diagnostic delay (DD). Aim of this study is to define presenting signs and natural history of SCID in a large cohort of patients, prior to hematopoietic stem cell or gene therapies. To this purpose, we conducted a 30-year retro-prospective multicenter study within the Italian Primary Immunodeficiency Network. One hundred eleven patients, diagnosed as typical or atypical SCID according to the European Society for Immune Deficiencies criteria, were included. Patients were subsequently classified based on the genetic alteration, pathogenic mechanism and immunological classification. A positive relationship between the age at onset and the DD was found. SCID patients with later onset were identified only in the last decade of observation. Syndromic SCIDs represented 28% of the cohort. Eight percent of the subjects were diagnosed in Intensive Care Units. Fifty-three percent had an atypical phenotype and most of them exhibited a discordant genotype-immunophenotype. Pre-treatment mortality was higher in atypical and syndromic patients. Our study broadens the knowledge of clinical and laboratory manifestations and genotype/phenotype correlation in patients with SCID and may facilitate the diagnosis of both typical and atypical forms of the disease in countries where newborn screening programs have not yet been implemented.

PMID: 31456805 [PubMed – in process]

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Diagnostic Approach to The Patients with Suspected Primary Immunodeficiency.

Endocr Metab Immune Disord Drug Targets. 2019 Aug 28;:

Authors: Tavakol M, Jamee M, Azizi G, Sadri H, Bagheri Y, Zaki-Dizaji M, Mahdavi FS, Jadidi-Niaragh F, Tajfirooz S, Kamali AN, Aghamahdi F, Noorian S, Kojidi HT, Mosavian M, Matani R, Dolatshahi E, Porrostami K, Elahimehr N, Fatemi-Abhari M, Sharifi L, Arjmand R, Haghi S, Zainaldain H, Yazdani R, Shaghaghi M, Abolhassani H, Aghamohammadi A

Abstract
BACKGROUND AND OBJECTIVE: Primary immunodeficiency diseases (PIDs) are a group of more than 350 disorders affecting distinct components of the innate and adaptive immune systems. In this review, the classic and advanced stepwise approach towards the diagnosis of PIDs are simplified and explained in detail.
RESULTS: Susceptibility to recurrent infections is the main hallmark of almost all PIDs. However, non-infectious complications attributable to immune dysregulation presenting with lymphoproliferative and/or autoimmune disorders are not uncommon. Moreover, PIDs could be associated with misleading presentations including allergic manifestations, enteropathies, and malignancies.
CONCLUSIONS: Timely diagnosis is the most essential element in improving outcome and reducing the morbidity and mortality in PIDs. This wouldn’t be possible unless the physicians keep the diagnosis of PID in mind and be sufficiently aware of the approach to these patients.

PMID: 31456526 [PubMed – as supplied by publisher]

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Clinical and Molecular Features of Chronic Granulomatous Disease in Mainland China and a XL-CGD Female Infant Patient After Prenatal Diagnosis.

J Clin Immunol. 2019 Aug 27;:

Authors: Wang S, Wang T, Xiang Q, Xiao M, Cao Y, Xu H, Li S, Tian W, Zhao X, Tang X, Jiang L

Abstract
PURPOSE: Chronic granulomatous disease (CGD) is the most common phagocyte defect disease. Here, we describe 114 CGD patients in our center and report a rare female infant with XL-CGD to provide a better understanding of diagnosis, treatment, and prenatal diagnosis of CGD.
METHOD: Patients were diagnosed by DHR-1,2,3 flow cytometry assays and gene analysis. X chromosome inactivation analysis and gp91phox protein test were used for a female infant with XL-CGD.
RESULTS: XL-CGD accounts for the majority of cases in China and results in higher susceptibility to some infections than AR-CGD. The DHR assay can help diagnose CGD quickly, and atypical results should be combined with clinical manifestations, genetic analysis, and regular follow-up. For prenatal diagnosis, both gDNA and cDNA genotypes of amniotic fluid cells should be identified, and cord blood DHR assays should be performed to identify female XL-CGD patients.

PMID: 31456102 [PubMed – as supplied by publisher]

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Acute cytomegalovirus infection in an immunocompetent patient with ulcerative colitis: A case report.

Exp Ther Med. 2019 Sep;18(3):2271-2277

Authors: Maeda T, Sakai H, Ozawa N, Sugiyama T, Takada J, Kubota M, Ibuka T, Shirakami Y, Araki H, Shimizu M

Abstract
Cytomegalovirus (CMV) is a ubiquitous member of the Herpesviridae family that can present with a variety of clinical manifestations, including encephalitis, retinitis, interstitial pneumonia and colitis. These serious symptoms are generally observed as opportunistic infections in immunocompromised hosts, including patients with acquired immunodeficiency syndrome and those receiving steroids and/or immunosuppressants. Symptomatic CMV infections in patients with ulcerative colitis are found in patients treated with steroids and/or immunosuppressants but rarely affect those who are not taking these agents. The present study reported the case of a young patient without concurrent use of immunosuppressive agents for the treatment of ulcerative colitis. The patient presented with acute mononucleosis and colitis caused by primary CMV infection. This was characterized by the presence of atypical lymphocytes and hepatosplenomegaly, elevation of transaminase levels, serology-positive anti-CMV IgM, and CMV antigenemia. Additionally, CMV-positive cells were histologically detected in colonic biopsy specimens. The patient’s symptoms and clinical parameters improved following initiation of intravenous ganciclovir. It was concluded that even if patients with ulcerative colitis are not treated with steroids and/or immunosuppressants, significant attention should be paid to acute CMV infections in the context of severe or persistent colonic inflammation.

PMID: 31452714 [PubMed]

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Malignancy in common variable immunodeficiency: a systematic review and meta-analysis.

Expert Rev Clin Immunol. 2019 Aug 27;:

Authors: Kiaee F, Azizi G, Rafiemanesh H, Zainaldain H, Sadaat Rizvi F, Alizadeh M, Jamee M, Mohammadi S, Habibi S, Sharifi L, Jadidi-Niaragh F, Yazdani R, Abolhassani H, Aghamohammadi A

Abstract
Background: Common variable immunodeficiency (CVID) is the most common clinically significant primary immunodeficiency (PID) disorder characterized by variable clinical manifestations including recurrent infections, autoimmune disorders, enteropathy, lymphoproliferative disorders and malignancy. The aim of this study is to estimate the overall prevalence of malignancy in patients with CVID. Methods: PubMed, Web of Science and Scopus were searched systemically to find eligible studies from the earliest available date to March 2019 with standard keywords. Pooled estimates of the malignancy prevalence and the corresponding 95% confidence intervals (CI) were calculated using random effects models. Results: Forty-eight studies with a total of 8123 CVID patients met the inclusion criteria and were finally included in the meta-analysis. Overall prevalence of malignancy was 8.6% (95% CI: 7.1-10.0; I2=79.2%). The prevalence of lymphoma, gastric cancer and breast cancer in CVID patients were 4.1% (95% CI: 3.3- 4.9; I2=62.6%), 1.5% (95% CI: 0.78-2.2; I2=68.9%), and 1.3% (95% CI: 0.64-1.9; I2=54.9%), respectively. Moreover, autoimmunity and malabsorption were more frequent in patients with malignancy than those without malignancy. Conclusion: The prevalence of malignancy has increased in CVID patients due to recent improvement in survival rate and the lymphoma is the most common type. This research highlighted the significance of malignancy screening and management in CVID patients.

PMID: 31452405 [PubMed – as supplied by publisher]

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Time-dependent decline of T cell receptor excision circle levels in ZAP-70 deficiency.

J Allergy Clin Immunol Pract. 2019 Aug 23;:

Authors: Suresh S, Dadi H, Reid B, Vong L, Bulman DE, Roifman CM

PMID: 31449923 [PubMed – as supplied by publisher]

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Polymerase δ deficiency causes syndromic immunodeficiency with replicative stress.

J Clin Invest. 2019 Aug 26;:

Authors: Conde CD, Petronczki ÖY, Baris S, Willmann KL, Girardi E, Salzer E, Weitzer S, Ardy RC, Krolo A, Ijspeert H, Kiykim A, Karakoc-Aydiner E, Förster-Waldl E, Kager L, Pickl WF, Superti-Furga G, Martínez J, Loizou JI, Ozen A, van der Burg M, Boztug K

Abstract
Polymerase δ is essential for eukaryotic genome duplication and synthesizes DNA at both the leading and lagging strands. The polymerase δ complex is a heterotetramer comprising the catalytic subunit POLD1 and the accessory subunits POLD2, POLD3, and POLD4. Beyond DNA replication, the polymerase δ complex has emerged as a central element in genome maintenance. The essentiality of polymerase δ has constrained the generation of polymerase δ-knockout cell lines or model organisms and, therefore, the understanding of the complexity of its activity and the function of its accessory subunits. To our knowledge, no germline biallelic mutations affecting this complex have been reported in humans. In patients from 2 independent pedigrees, we have identified what we believe to be a novel syndrome with reduced functionality of the polymerase δ complex caused by germline biallelic mutations in POLD1 or POLD2 as the underlying etiology of a previously unknown autosomal-recessive syndrome that combines replicative stress, neurodevelopmental abnormalities, and immunodeficiency. Patients’ cells showed impaired cell-cycle progression and replication-associated DNA lesions that were reversible upon overexpression of polymerase δ. The mutations affected the stability and interactions within the polymerase δ complex or its intrinsic polymerase activity. We believe our discovery of human polymerase δ deficiency identifies the central role of this complex in the prevention of replication-related DNA lesions, with particular relevance to adaptive immunity.

PMID: 31449058 [PubMed – as supplied by publisher]

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Consensus on updating immunizations in patients with primary immunodeficiencies

Arch Argent Pediatr. 2018 04 01;116(2):s20-s33

Authors: Comité Nacional de Infectología, Grupo de Trabajo de Inmunología

PMID: 29775036 [PubMed – indexed for MEDLINE]

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