Retinal Occlusive Vasculitis in a Patient with Hyperimmunoglobulin E Syndrome

Background. Hyperimmunoglobulin E syndrome (HIES), or Job’s syndrome, is a primary immunodeficiency disorder that is characterized by an elevated level of IgE with values reaching over 2000 IU ( normal < 200 IU ), eczema, and recurrent staphylococcus infection. Affected individuals are predisposed to infection, autoimmunity, and inflammation. Herein, we report a case of HIES with clinical findings of retinal occlusive vasculitis. Case Presentation. A 10-year-old boy with a known case of hyperimmunoglobulin E syndrome had exhibited loss of vision and bilateral dilated fixed pupil. Fundoscopic examination revealed peripheral retinal hemorrhaging, vascular sheathing around the retinal arteries and veins, and vascular occlusion in both eyes. A fluorescein angiography of the right eye showed hyper- and hypofluorescence in the macula and hypofluorescence in the periphery of the retina, peripheral arterial narrowing, and arterial occlusion. A fluorescein angiography of the left eye showed hyper- and hypofluorescence in the supranasal area of the optic disc. Macular optical coherence tomography of the right eye showed inner and outer retinal layer distortion. A genetic study was performed that confirmed mutations of the dedicator of cytokinesis 8 (DOCK 8). HSV polymerase chain reaction testing on aqueous humor and vitreous was negative, and finally, the patient was diagnosed with retinal occlusive vasculitis. Conclusion. Occlusive retinal vasculitis should be considered as a differential diagnosis in patients with hyperimmunoglobulin E syndrome presenting with visual loss.

Human immune globulin 10% with recombinant human Hyaluronidase- A Review

Primary immunodeficiency disorder (PID) refers to a heterogeneous cluster of over 350 syndromes that upshot from defects in the immune system development or function. PIDs are broadly classified as disorders of adaptive immunity or innate immunity. The enhanced efficacy of human immune serum globulin 10% with recombinant human Hyaluronidase with comparison to blood vessel human gamma globulin is a very prospective open-label study for PID. Treatment of primary immunological disorder diseases (PIDD) with Subcutaneous(SC) infusions of immune gamma globulin headed by an injection of hyazyme to extend SC tissue porousness was evaluated in two consecutive, prospective, non-controlled, multi-center studies. HYQVIA could be a subcutaneously mediated medication to treat the primary immunological disorder in adults. ENHANZE® drug delivery technology relies on the proprietary rHuPH20 macromolecule that facilitates the SC delivery of co administered medical specialty. Recombinant Human Hyaluronidase works by degrading the glycosaminoglycan hyaluronan, which plays a role in resistance to excessive flow of fluid within the Subcutaneous matrix, limiting massive volume SC drug delivery, dispersion, and absorption. Co-administration of recombinant Hyazyme with partner therapies can overcome administration time and volume barriers associated with existing SC therapeutic formulations.

Whole genome sequencing identifies novel structural variant in a large Indian family affected with X-linked agammaglobulinemia

X—linked agammaglobulinemia (XLA, OMIM #300755) is a primary immunodeficiency disorder caused by pathogenic variations in the BTK gene, characterized by failure of development and maturation of B lymphocytes. The estimated prevalence worldwide is 1 in 190,000 male births. Recently, genome sequencing has been widely used in difficult to diagnose and familial cases. We report a large Indian family suffering from XLA with five affected individuals. We performed complete blood count, immunoglobulin assay, and lymphocyte subset analysis for all patients and analyzed Btk expression for one patient and his mother. Whole exome sequencing (WES) for four patients, and whole genome sequencing (WGS) for two patients have been performed. Carrier screening was done for 17 family members using Multiplex Ligation-dependent Probe Amplification (MLPA) and haplotype ancestry mapping using fineSTRUCTURE was performed. All patients had hypogammaglobulinemia and low CD19+ B cells. One patient who underwent Btk estimation had low expression and his mother showed a mosaic pattern. We could not identify any single nucleotide variants or small insertion/ deletions from the WES dataset that correlates with the clinical feature of the patient. Structural variant analysis through WGS data identifies a novel large deletion of 5,296 bp at loci chrX:100,624,323–100,629,619 encompassing exons 3–5 of the BTK gene. Family screening revealed seven carriers for the deletion. Two patients had a successful HSCT. Haplotype mapping revealed a South Asian ancestry. WGS led to identification of the accurate genetic mutation which could help in early diagnosis leading to improved outcomes, prevention of permanent organ damage and improved quality of life, as well as enabling genetic counselling and prenatal diagnosis in the family.

Republican registry of primary immune deficiencies in the chuvash republic and description of postvaccinal immunity disorders in a pregnant patient with common variable immune deficiency

In recent years, primary immunodeficiencies have turned from the class of rare diseases to the category of more common disorders which may be encountered by doctors of any clinical discipline. The first case of primary immunodeficiency disorder (PID) in Chuvashia was detected in 1993. Since that time, the Department of Internal Diseases with the Course of Clinical Immunology at the I. Ulyanov Chuvash State University registered all the cases of PID diagnosed in the region, introducing them into the Republican Registry of PID. The study was aimed for searching epidemiological indexes, clinical and laboratory manifestations of PID in Chuvash region. The study was based on the patient data obtained by retrospective analysis of 85 case histories of PID patients, treated at different departments of the Republican Clinical Hospital, and the City Chuvash Pediatric Clinical Hospital of Public Health Ministry in 2000-2019, as well as on 49 outpatient records of the patients included into the Regional PID Registry. Various forms of PIDs were diagnosed according to the criteria developed by the European Society for Immunodeficiency and the Pan-American Group on Immunodeficiency (1999). The results of this study showed that the incidence of PID in the Chuivash Region is 3.4:100,000. The incidence of common variable immune deficiency (CVID), the most common form of PID in the region, was 1.58 per 100,000 population. The average age at the time of CVID diagnosis in Chuvash patients was 30.4±16.1 years, and the age of CVID debut was 11.3±15.0 years. The delay in proper diagnosis from the moment of clinical manifestation of CVID was, on average, 17.9 years in the region. At the time of CVID diagnosis, the patients showed marked decrease in the levels of 3 or 2 immunoglobulin classes (IgG and IgA), and T-helper cell contents (CD3+CD4+) in peripheral blood. Prevalence of selective IgA deficiency with сlinical symptoms was 0.83 per 100,000 population of the region, and the incidence of the asymptomatic form of this PID was 1 : 167. In patients with selective IgA deficiency, there were also disorders in the T cell system manifesting as decreased relative number of cytotoxic T-cells as well as elevated IgG and IgM levels. The age of diagnosis of X-linked agammaglobulinemia in the region was 3.5±3.0 years. In addition to disturbances of humoral adaptive immunity in children with this disease, a decrease in absolute T cell numbers was detected. In conclusion, the article describes disturbances of postvaccinal immunity in a pregnant patient with CVID, with asymptomatic clinical course, thus leading to false interpretation of the serological markers of TORCH infections and wrong strategy of pregnancy management.

A chronic granulomatous disease masked by tuberculosis in a 2-year, 2-month old child: a case report

Chronic granulomatous disorder is a rare primary immunodeficiency disorder with phagocytic defect resulting in recurrent bacterial infections. Here we report a 2-year 2-month old male child, who presented with recurrent lymphadenitis and recurrent pneumonia since early infancy. In recent episode he presented with right cervical lymphadenopathy. Biopsy of lymph node revealed confluent necrotizing epithelioid cell granulomas and occasional giant cells but without evidence of tuberculosis and atypical organisms. His dihydrorhodamine 1,2,3 assay (DHR) was positive. Later he responded to prolonged parenteral antibiotics and discharged on itraconazole and trimethoprim-sulhamethaxazole prophylaxis. Here we are going to report a rare case of chronic granulomatous disease whose diagnosis was masked by tuberculosis

Recurrent somatic mutations and low germline predisposition mutations in Korean ALL patients

In addition to somatic mutations, germline genetic predisposition to hematologic malignancies is currently emerging as an area attracting high research interest. In this study, we investigated genetic alterations in Korean acute lymphoblastic leukemia/lymphoma (ALL) patients using targeted gene panel sequencing. To this end, a gene panel consisting of 81 genes that are known to be associated with 23 predisposition syndromes was investigated. In addition to sequence variants, gene-level copy number variations (CNVs) were investigated as well. We identified 197 somatic sequence variants and 223 somatic CNVs. The IKZF1 alteration was found to have an adverse effect on overall survival (OS) and relapse-free survival (RFS) in childhood ALL. We found recurrent somatic alterations in Korean ALL patients similar to previous studies on both prevalence and prognostic impact. Six patients were found to be carriers of variants in six genes associated with primary immunodeficiency disorder (PID). Of the 81 genes associated with 23 predisposition syndromes, this study found only one predisposition germline mutation (TP53) (1.1%). Altogether, our study demonstrated a low probability of germline mutation predisposition to ALL in Korean ALL patients.

Wiskott-Aldrich Syndrome

The Wiskott-Aldrich syndrome (WAS) could be a rare X-linked primary immunodeficiency disorder characterized by recurrent infections, eczema, and bleeding following thrombocytopenia. Despite the rarity of this syndrome, today our understanding of the cellular and molecular basis of the pathogenesis of this disease has increased and it’s well established that this disorder encompasses a wide range of clinical disorders including immunodeficiency, atopy, autoimmunity, and cancer. Wiskott–Aldrich Syndrome protein (WASP) mutations are located throughout the gene and inhibit or regulate the conventional function of WASP. Thus classic WAS occurs when WASP is absent, X-linked thrombocytopenia when mutated WASP is expressed, and X-linked neutropenia when missense mutations occur within the Cdc42-binding site. Developments within the use of diagnostic tools, supportive care, and advances in allogeneic hematopoietic cell transplantation have remarkably reduced the mortality related to this disorder. Besides, gene therapy has provided optimistic perspectives on the treatment approaches of those patients.

Chronic Diarrhea in Children: Experience at A Tertiary Hospital of Bangladesh

Background: Chronic diarrhea is insidious onset that persists for 14 days and more, usually of noninfectious origin. Chronic diarrhea in children is not an uncommon problem in our country. Objectives: Objective of this study was to evaluate children with chronic diarrhea by clinical-biochemical profile and outcome. Methods: It was a retrospective observational study done in the department of paediatric gastroenterology and nutrition, BSMMU. The study was done during January 2017 through December 2018. Forty-five patients diagnosed as chronic diarrhea between the ages of 6 months to 18 years were included in this study. We Clinical, laboratory data and outcome of patients were analyzed. Results: Mean age of children was 5.96±2.3 year, 60%(27) were male and 40% (18) were female. Among them under 5 years were 55%(25). All children presented with diarrhea (100%) along with fever (24%), FTT (22%), abdominal pain (20%) and weight loss (20%). About 58% of children had anemia and 14% had hepatomegaly and/or splenomegaly. Raised ESR (40%), leukocytosis (20%), thrombocytosis (16%), raised CRP (13%) and electrolyte imbalance (16%) were observed. Intestinal TB (18%) was the most common etiology of chronic diarrhea. Moreover, chronic constipation with fecal incontinence mimicking diarrhea (11%), IBD (9%), coeliac disease (8%), IBS (7%), HIV enteropathy (4%), primary immunodeficiency disorder (4%) were also found. Improvement of diarrhea was observed in 96% children, 4% patient died due to diarrhea-related complications. Conclusion: Chronic diarrhea in children is not uncommon in Bangladesh and diagnosis of etiologies are challenging. Intestinal tuberculosis found to be an important cause of chronic diarrhea in this study. Although in the majority of the cases, etiology could not be identified, some remote etiologies were found on this study, like chronic constipation with fecal incontinence mimicking diarrhea, IBD, HIV enteropathy, primary immunodeficiency. DS (Child) H J 2020; 36(1) : 46-51

Clinical and Laboratory Findings in Patients with Leukocyte Adhesion Deficiency Type I: A Multicenter Study in Turkey

Leukocyte adhesion deficiency type I is rare primary immunodeficiency disorder characterized by mutations in the ITGB2 gene encoding CD18. We present clinical and immunological features of 15 patients with leukocyte adhesion deficiency type I (LAD-I). Targeted next-generation sequencing was performed with either a primary immunodeficiency gene panel comprising 266 genes or a small LAD-panel consisting of five genes for genetic analysis. To measure the expression level of integrins on the leukocyte surface, flow cytometry analysis was performed. The median age of the patients at diagnosis was 3 (1-48) months. Eleven (73%) of the 15 patients had LAD-I diagnosis in their first 6 months, and fourteen (93%) patients had consanguineous parents. Delayed separation of the umbilical cord was present in 80% (n=12) of the patients in our cohort, whereas omphalitis was observed in 53% (n=8) of the patients. Leukocytosis with neutrophil predominance was observed in 73% (n=11) patients. Nine distinct variants in the ITGB2 gene in 13 of the 15 patients with LAD-I were characterized, of which two (c.305_306delAA and c.779_786dup) are novel homozygous mutations of ITGB2 . Four unrelated patients from Syria had a novel c.305_306delAA mutation that might be a founder effect for patients of Syrian origin. Four (27%) patients underwent HSCT. Two of them died because of HSCT complications, and the other two are alive and well. Early differential diagnosis of the patients is critical in the management of the disease and genetic evaluation provides a basis for family studies and genetic counseling.

Turning walking pneumonia into recurrent abscesses: a curious case of CVID and review of the literature

Background: common variable immunodeficiency (CVID) is a primary immunodeficiency disorder associated with a broad symptom presentation that is still being characterized. We report a rare case of recurrent mycoplasma skin abscesses in a patient with a history of autoimmune disorders and prolonged mycoplasma pneumonia who was diagnosed with CVID.Case presentation: a 34-year-old woman presented with a history of recurrent abscesses previously confirmed positive for Mycoplasma pneumoniae. Her past medical history of recurrent mycoplasma abscesses, prolonged mycoplasma pneumonia, and autoimmune disorders (mixed connective tissue disease and immune thrombocytopenia) raised suspicion of CVID. Workup included negative anti-mycoplasma antibody titers, hypogammaglobulinemia, and negative anti-pneumococcal antibody titers despite prior vaccination, solidifying the diagnosis of CVID. The patient was discharged on antibiotic and intravenous immunoglobulin therapy with improvement and now follows allergy and immunology long-term for treatment.Conclusions: her diagnostic history underscores the importance of considering the various criteria of CVID for diagnosis, and her unique presentation of M. pneumoniae skin abscesses highlights the broad sequelae patients with CVID can manifest.