Neurological Manifestations of Primary Immunodeficiencies

Primary immunodeficiencies (PID) are a heterogeneous group of disorders  with a variable clinical spectrum of manifestations. The central nervous system may be involved in PIDs with symptoms which may present initially or develop at later stages. Neurological manifestations of primary immunodeficiencies are common with diverse pathologic mechanisms. Neurological deficits may be mild or they may greatly influence the course of the disease with major impacts on the quality of life of the patients. Physical examination may give the clinician valuable clues to the cause of PIDs that underlie the neurological signs. Certain neurological abnormalities may later signify a PID. Therefore physicians should be aware of the neurological features accompanying immunodeficiencies.  Neuromascular abnormality presenting with ataxia(ataxia-telangiectasia) , flaccid paralysis after live poliovirus immunization (combined or antibody deficiencies) ,pernicious anaemia (CVID), cognitive impairment, nystagmus and cerebellar, spinal and peripheral neuropathies(Chediac-Higashi syndrome), seizures, ataxia and occulomotor and reflex abnormalities(Griscelli syndrome) are examples of neurologic features seen in different immunodeficiency syndromes. Early recognition and treatment is important to prevent or reduce future irreversible neurological sequelae. The aim of this study is to review the neurological manifestations of different primary immunodeficiency syndromes

Disseminated Bacille Calmette-Guérin infection at a glance: a mini review of the literature

Introduction: Immunodeficient children are at a high risk of disseminated Bacillus Calmette-Guérin [BCG] infection. We assessed the literature on clinical manifestations of BCGosis in children with specific primary immunodeficiencies. Material and methods: We conducted a systematic review of clinical practice articles by searching Medline, PubMed, Embase, Scopus, Web of Science and Google Scholar from their inception to date. Results: Thirty-seven articles were included regarding BCG vaccination and its dissemination in children with primary immunodeficiencies. Articles on dissemination after intravesicular BCG were excluded from the study. Conclusions: Since disseminated BCG vaccination may be the first manifestation of a primary immunodeficiency disease, a comprehensive search for immunological defects in children developing these problems after BCG vaccination seems rational

Long term outcome of cystic fibrosis patients with multisystem evaluation

  INTRODUCTION: Cystic fibrosis is a chronic disease with multiple organ involvement and chiefly results in chronic respiratory infections, pancreatic insufficiency and associated complications. The age at diagnosis, clinical presentation, rate of disease progression and prognosis is variable among patients. This study is designed to evaluate the behavior of disease to provide epidemiologic data for early recognition and proper management. MATERIAL AND METHODS: The study was designed as an active surveillance of 192 patients diagnosed with cystic fibrosis in a tertiary lung disease centre between 2008 and 2015. The diagnosis of cystic fibrosis was established in all patients accordingly to conventional criteria, including two positive sweat chloride tests and clinical signs and symptoms. Demographic, clinical and laboratory data were obtained from these patients in each hospitalization and also every follow-up visit and carefully evaluated for complications of this chronic disease. RESULTS: The majority of patients showed positive culture for Pseudomonas aeroginosa. Bronchiectasis was the most prevalent finding in chest CT scan. 44.3% of patients had been treated for allergic bronchopulmonary aspergillosis and all had sinus disease. Increased pulmonary artery pressure was observed in 40% of patients with cystic fibrosis. 33 patients died which consisted 17.1% of all the patients.The mean age of mortaliy was 18.15 year. CONCLUSIONS: The clinical outcome of cystic fibrosis is variable in different countries which may reflect environmental influences and the role of early diagnosis on long term outcomes. However, the role of early diagnosis in long-term outcomes of the disease can not be ignored.

Kompleksowa ocena długoterminowa chorych na mukowiscydozę

WSTĘP: Mukowiscydoza jest wielonarządową chorobą przewlekłą, której głównymi następstwami są infekcje układu oddechowego, niewydolność trzustki i inne pokrewne powikłania. Wiek w czasie rozpoznania, przebieg kliniczny, tempo progresji i rokowanie są różne u różnych chorych. Celem prezentowanego badania była ocena przebiegu choroby i wpływu uwarunkowań epidemiologicznych na wczesne rozpoznanie i właściwe leczenie. MATERIAŁ I METODY: Przeprowadzono aktywną ocenę prospektywną 192 chorych na mukowiscydozę, leczonych w ośrodku referencyjnym w latach 2008–2015. U wszystkich chorych rozpoznanie mukowiscydozy postawiono na podstawie obowiązujących kryteriów, w tym stwierdzenia dwóch dodatnich wyników potowego testu chlorkowego oraz obecności typowych objawów klinicznych. Dane demograficzne, kliniczne i laboratoryjne uzyskiwano od pacjentów podczas kolejnych hospitalizacji i wizyt kontrolnych. Dane te były szczegółowo oceniane pod kątem powikłań choroby podstawowej. WYNIKI: U większości chorych stwierdzono dodatni wynik hodowli plwociny w kierunku Pseudomonas aeroginosa. Rozstrzenia oskrzeli były najczęściej występującym objawem w badaniu tomograficznym klatki piersiowej. W badanej grupie 44,3% chorych było leczonych z powodu alergicznej aspergilozy oskrzelowo-płucnej a u wszystkich chorych stwierdzono chorobę zatok przynosowych. Podwyższone ciśnienie w tętnicy płucnej stwierdzono u 40% chorych na mukowiscydozę. Zmarło 33 chorych, co stanowi 17,1% badanej grupy. Średni czas przeżycia wynosił 18,15 roku. WNIOSKI: Wyniki leczenia chorych na mukowiscydozę są różne w różnych krajach, co może odzwierciedlać wpływy środowiska, a także znaczenie wczesnego rozpoznania dla odległego rokowania. Znaczenie wczesnego rozpoznania dla odległych wyników leczenia nie powinno być lekceważone.WSTĘP: Mukowiscydoza jest wielonarządową chorobą przewlekłą, której głównymi następstwami są infekcje układu oddechowego, niewydolność trzustki i inne pokrewne powikłania. Wiek w czasie rozpoznania, przebieg kliniczny, tempo progresji i rokowanie są różne u różnych chorych. Celem prezentowanego badania była ocena przebiegu choroby i wpływu uwarunkowań epidemiologicznych na wczesne rozpoznanie i właściwe leczenie. MATERIAŁ I METODY: Przeprowadzono aktywną ocenę prospektywną 192 chorych na mukowiscydozę, leczonych w ośrodku referencyjnym w latach 2008–2015. U wszystkich chorych rozpoznanie mukowiscydozy postawiono na podstawie obowiązujących kryteriów, w tym stwierdzenia dwóch dodatnich wyników potowego testu chlorkowego oraz obecności typowych objawów klinicznych. Dane demograficzne, kliniczne i laboratoryjne uzyskiwano od pacjentów podczas kolejnych hospitalizacji i wizyt kontrolnych. Dane te były szczegółowo oceniane pod kątem powikłań choroby podstawowej. WYNIKI: U większości chorych stwierdzono dodatni wynik hodowli plwociny w kierunku Pseudomonas aeroginosa. Rozstrzenia oskrzeli były najczęściej występującym objawem w badaniu tomograficznym klatki piersiowej. W badanej grupie 44,3% chorych było leczonych z powodu alergicznej aspergilozy oskrzelowo-płucnej a u wszystkich chorych stwierdzono chorobę zatok przynosowych. Podwyższone ciśnienie w tętnicy płucnej stwierdzono u 40% chorych na mukowiscydozę. Zmarło 33 chorych, co stanowi 17,1% badanej grupy. Średni czas przeżycia wynosił 18,15 roku. WNIOSKI: Wyniki leczenia chorych na mukowiscydozę są różne w różnych krajach, co może odzwierciedlać wpływy środowiska, a także znaczenie wczesnego rozpoznania dla odległego rokowania. Znaczenie wczesnego rozpoznania dla odległych wyników leczenia nie powinno być lekceważone

Janus-kinase Inhibitors in Pathogenesis and Management of Chronic Urticaria: A Review of the Literature

Background: Chronic urticaria is a long-lasting condition, sometimes with serious comorbidities, severely affecting the quality of life, which makes the patients seek efficient therapies to achieve sustained remissions. The complex nature of urticaria greatly complicates the patients’ responses to appropriate treatments.  Objectives: This review was conducted to focus on the Janus kinase (JAK) pathway, evaluate its role as a new biomarker, and discover the efficacy of its inhibitors as novel therapeutic agents in the treatment of refractory chronic urticaria. Methods: Electronic databases of PubMed and SCOPUS were searched to find and evaluate all the reports describing “Janus kinase,” “JAK-STAT pathway,” “chronic urticaria,” “JAK inhibitors,” and “pruritus.” Because itching is the most annoying symptom of chronic urticaria and due to the scarcity of articles conducted on the use of JAK inhibitors in the treatment of this disease, we also reviewed quite a few articles performed on applying JAK inhibitors in the treatment of dermatologic disorders and also pruritus in atopic dermatitis. Results: From the initially retrieved articles, only five were exclusively about the use of JAK inhibitors in the treatment of chronic urticaria. Conclusions: Although JAK inhibitors are widely known as effective therapies in the treatment of some dermatological diseases, we found out that there are not currently sufficient eligible studies confirming the role of JAK inhibitors in the treatment of chronic urticaria. There is therefore a need for more studies regarding the efficacy and safety of these medications in the treatment of refractory chronic urticaria

Disseminated Bacille Calmette-Guérin Infection at a Glance: A Mini Review of the Literature

Introduction: Immunodeficient children are at a high risk of disseminated Bacillus Calmette-Guérin [BCG] infection. We assessed the literature on clinical manifestations of BCGosis in children with specific primary immunodeficiencies. Material and methods: We conducted a systematic review of clinical practice articles by searching Medline, PubMed, Embase, Scopus, Web of Science and Google Scholar from their inception to date. Results: Thirty-seven articles were included regarding BCG vaccination and its dissemination in children with primary immunodeficiencies. Articles on dissemination after intravesicular BCG were excluded from the study. Conclusions: Since disseminated BCG vaccination may be the first manifestation of a primary immunodeficiency disease, a comprehensive search for immunological defects in children developing these problems after BCG vaccination seems rational

Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort

Background: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses. Objective: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings. Methods: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID. Results: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 μ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with μ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with μ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008). Conclusions: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment

Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort

Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses