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- OPEN ACCESSIntroduction: The epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), continues to affect most of the world’s population. In children, the respiratory and systemic involvement appears to have a much more benign course in comparison to adults, with almost no fatalities reported. However, we are now encountering a post-infectious immune mediated condition, termed, multisystem inflammatory syndrome in children (MIS-C). In most cases the main features are prolonged fever and elevated inflammatory markers. Many of the patients present with abdominal pain and varying degrees of myocardial involvement, from mild reduction in cardiac output to the most alarming manifestation of cardiovascular shock.Results: We present two patients with unusual manifestations of MIS-C related to post COVID-19 infection: an infant born to a mother who was severely ill at the very end of pregnancy, presenting with prolonged fever, rash, pericardial effusion, and evidence of coronary arteries wall dilation thickening as a result of inflammation, and, a teenage girl with severe cardiac tamponade without the more common cardiac manifestations of myocardial involvement.Discussion: Post COVID-19 MIS-C can present with a wide variety of manifestations. The pathophysiologic mechanisms underlying these inflammatory responses in infants are yet to be elucidated. Physicians should be aware of such presentations since rapid diagnosis and treatment are key for a favourable outcome.Statement of novelty: We present two unique manifestations of post COVID-19 infection which, to date, are not discussed frequently in the literature.
- OPEN ACCESSIntroduction: Common Variable Immune Deficiency (CVID) is the most prevalent form of severe antibody deficiency in children and adults. Most patients suffer recurrent, mainly sinopulmonary, infections. Despite adequate IVIG replacement therapy, chronic lung disease continues to be a main cause of morbidity and mortality. The term granulomatous-lymphocytic interstitial lung disease (GLILD) is frequently used to describe interstitial lung disease associated with immune dysregulation in primary antibody deficiency, such as CVID.Aim: To describe the case of a 10-year-old male with CVID who developed GLILD and his response to treatment with Rituximab.Discussion: Our patient is a young male with CVID and no genetic diagnosis, whose lung functions and general condition continued to deteriorate despite adequate intravenous immunoglobulin replacement therapy and mycophenolate mofetil treatment. After the diagnosis of GLILD, we initiated treatment with a 4-dose weekly course of Rituximab with prompt resolution of his interstitial disease. Although GLILD is a well described condition that accompanies CVID as a manifestation of immune dysregulation, it is still under recognized, especially in the pediatric population. Among experts, there is little uniformity when it comes to diagnostic and treatment approaches. Recent studies showed improved outcomes when using combination therapy with Rituximab, such as in our patient.Statement of Novelty: We shed light on GLILD, an important condition that accompanies CVID, and demonstrate an excellent response to the steroid sparing agent Rituximab. This is a crucial aspect when considering therapeutic choices for the pediatric population.
- OPEN ACCESS
- Adebayo Lawrence Adedeji,
- Dauda Jimoh,
- Jelili Abiodun Badmus,
- Ibrahim Olabanji Bello,
- Ibrahim Eleha Suleiman, and
- Olubunmi Gloria Ayelagbe
Background: Serum protein abnormalities, particularly elevated gamma globulins (hypergammaglobulinemia, HGG), have been reported in apparently healthy Nigerians living in Ogbomoso and elsewhere. Since the mechanisms for this phenomenon have not been fully substantiated, we hypothesized that impaired neutrophil phagocytosis could contribute to this condition.Methods: Healthy humans exhibiting HGG were identified using serum protein electrophoresis performed on cellulose acetate gel in barbital buffer (pH 8.6). GelQuant image analysis and quantitation software were further employed to quantify the gamma globulin fraction. Neutrophils were isolated from K3EDTA anticoagulated peripheral blood using Histopaque neutrophil isolation reagent. Neutrophil phagocytic activity was analyzed using a non-subjective commercial colorimetric phagocytosis assay kit.Results: The purity and viability of isolated neutrophils were approximately 94% and 92%, respectively. Ex-vivo phagocytic activity of neutrophils isolated from apparently healthy subjects exhibiting HGG, expressed as a percentage of the average absorbance of the control group, was 48.1 ± 8.6% which was significantly lower (p < 0.05) compared to the controls (98.9 ± 14.3%).Conclusion: Since neutrophils play crucial roles in innate immune responses, impairment of neutrophil phagocytic activity may lead to persistent antigenic stimulations of the adaptive immune system. This could in turn orchestrate gamma globulins expression leading to HGG.Statement of novelty: We demonstrated reduced neutrophil phagocytic activity as a possible basis for hypergammaglobulinemia in healthy Nigerians, perhaps for the first time. - OPEN ACCESSIntroduction: The impact of SARS-CoV-2 infections in children has generally been described as relatively benign. However, since April 2020, there have been reports of a new multisystem inflammatory illness affecting children and related to COVID-19 termed multisystem inflammatory syndrome in children (MIS-C).Aim: To describe 3 cases of children diagnosed with MIS-C and discuss the disease spectrum.Methods: We collected and reviewed data from 3 cases diagnosed with MIS-C admitted to our pediatric ward between October 2020 and January 2021.Discussion: MIS-C is a newly described disease that spans a spectrum of phenotypes and severity, and while it shares clinical similarities with Kawasaki disease, it has a unique set of epidemiological, laboratory, and prognostic characteristics. In this review, we hope to add to the understanding of this new entity.Statement of Novelty: This report discusses 3 cases of MIS-C and elaborates on the spectrum and immunology of this entity. Our cases are unique in their relatively wide spectrum and variability. We hope our own experience with MIS-C adds to the accumulating knowledge and understanding of this emerging disease.
- OPEN ACCESSBackground: Coronavirus disease 2019 (Covid-19) remains a pandemic with multiple challenges to confirm patient infectivity: lack of sufficient tests, accurate results, validated quality, and timeliness of results. We hypothesize that a rapid 15-minute Point-Of-Care serological test to evaluate past infection complements diagnostic testing for Covid-19 and significantly enhances testing availability.Method: A three arm observational study at Sharp Healthcare, San Diego, California was conducted using the Clungene® lateral flow immunoassay (LFI) and compared with the Cobas® Roche real-time polymerase chain reaction (RT-PCR) results. Arm 1: Thirty-five (35) subjects with confirmed Covid-19 using RT-PCR were tested twice: prior to 14 days following symptom onset and once between 12 and 70 days. Arm 2: Thirty (30) subjects with confirmed Covid-19 using RT-PCR were tested 12-70 days post symptom onset. Arm 3: Thirty (30) subjects with a negative RT-PCR for Covid-19 were tested 1–10 days following the RT-PCR test date.Results: Specificity of confirmed negative Covid-19 by RT-PCR was 100% (95% CI, 88.4%–100.0%); meaning there was 100% negative positive agreement between the RT-PCR and the Clungene® serological test results. Covid-19 subjects tested prior to day 7 of symptom onset were antibody negative. In subjects 7–12 days following symptom onset with a confirmed positive Covid-19 by RT-PCR, the combined sensitivity of IgM and IgG was 58.6% (95% CI, 38.9%–76.5%). In subjects 13–70 days following symptom onset with a confirmed positive Covid-19 by RT-PCR, the combined sensitivity of IgM and IgG was 90.5% (95% CI, 80.4%–96.4%).Conclusion: The Clungene® lateral flow immunoassay (LFI) is a useful tool to confirm individuals with an adaptive immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) indicating past infection. Providing Point-Of-Care results within 15 minutes without any laboratory instrumentation or specialized software has an added value of increasing test availability to patients who have been symptomatic for more than 1 week to confirm past infection. Performance characteristics are optimal after 13 days with a sensitivity and specificity of 90% and 100%, respectively.Statement of novelty: Formal controlled clinical studies of Covid-19 antibody tests have been limited. This study demonstrates the utility of the 15 minute rapid Clungene® test and the potential for expanded use where Covid-19 RT-PCR testing and vaccination is limited.
- OPEN ACCESSBackground: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The application of point of care serological testing can help determine past infection and assist healthcare workers assess patient risk.Method: An observational study of 114 subjects in North Suburban Chicago, Illinois, was performed using the Clungene® lateral flow immunoassay (LFI). Patients’ PCR test results and clinical symptoms were used to compare the seroconversion rate of this patient population with the surrounding community.Results: Excluding 1 aberrant result, there was 100% positive agreement (10) between PCR and antibody (IgG or IgM) test results. There were 7 patients who did not have a prior PCR test who were positive for IgG; 5 of the 7 had clinical symptoms consistent with possible exposure and 2 were asymptomatic. There was 1 person with a suspected exposure to an infected person who was IgM positive. Ninety-five asymptomatic patients were seronegative. The overall rate of 15.9% seroconversion (IgG or IgM) is consistent with other community-based testing results in the North Suburban Chicago, Illinois area.Conclusion: Rapid screening tests to identify antibody positive patients recovered from coronavirus disease-2019 can be a useful tool for healthcare professionals to determine or confirm past infection.Statement of novelty: Limited data is available on the use of point of care serological testing to assist healthcare professionals with the assessment of their patient population regarding past SARS-CoV-2 infectivity and seroconversion. The present study successfully investigated the use of a point of care antibody test in a physician’s office to determine which patients have developed antibodies, indicating an immune response to SARS-CoV-2, and to assist with decisions on whether patients should pursue normal social and workplace activities.
- OPEN ACCESSObjectives: To assess the psychological effects of systemic lupus erythematosus (SLE), including perception of aging, in a cohort of participants who were either diagnosed with SLE or had an affected family member.Methods: Over a period of 1 year, we conducted once-monthly face-to-face interviews with 12 participants. The participants were from 4 related families and include 7 females and 5 males. Three participants had a confirmed diagnosis of SLE. Spouses were also included in this study to assess transitivity of the psychological signs of SLE. Responses to structured interview questions were analyzed to assess the perception of aging.Results: The major complaints in participants diagnosed with SLE were pain and psychological stress. Nephrotic syndrome, urinary tract infection, weight disorders and increased need for psychosocial support were common in the participants’ medical history. Qualitative analysis of questionnaires completed by participants with SLE revealed a correlation of “feeling old” with the non-resolution of health complaints. Family members who did not have SLE also reported “feeling old”. Complaints of stress, anxiety, nervousness and lack of enjoyment of life were common in those who were diagnosed with SLE, as well as those who were not. All spouses reported experiencing digestive disorders, hemorrhoids as well as various phobias, regardless of whether their partners had a confirmed SLE diagnosis.Conclusions: In this study, we found that participants with SLE or those who had a close family member with SLE displayed psychological signs of aging. All participants had a predisposition to anxiety, while spouses developed various phobias.Statement of novelty: We show that individuals with SLE and close family members have an increased self-perception of aging.
- OPEN ACCESS
- Mehdi Yeganeh,
- Tallal Basha,
- Lina Sobhi Abdrabo,
- Sophie Ran Wang,
- Joël Lafond-Lapalme,
- Jean-Baptiste Rivière,
- Duncan Lejtenyi,
- David S. Rosenblatt,
- Christine McCusker,
- Reza Alizadehfar, and
- Bruce D. Mazer
Background: Patients with chromosome 18 abnormalities can present with an immune phenotype that resembles common variable immunodeficiency. Knowledge of the genes underlying the immune defects related to chromosome 18 aberrations could improve our understanding of the molecular basis of primary antibody deficiencies. Here we present a patient with ring chromosome 18 affected by primary antibody deficiency and autoimmunity.Methods: Lymphocyte populations were determined by flow cytometry. Specific antibody response to protein vaccines and pneumococcal capsule antigen were measured by ELISA. Genome sequencing was performed using a PCR-free protocol.Case: The patient was diagnosed with ring chromosome 18 for delayed growth and dysmorphic features at the age of 1 month. Array comparative genomic hybridization showed deletions of 18p11.21-pter and 18q21.31-qter. At the age of 10 months, she started having recurrent episodes of otitis media and pneumonia, as well as autoimmune arthritis. Serum immunoglobulins and specific antibody levels were low. The CD19+CD27+ memory B cell and CD45RO+ T cell populations were decreased. Recurrent infections were controlled with parenteral immunoglobulin and autoimmune arthritis was treated with systemic and intra-articular therapies.Conclusions: Selective IgA deficiency is the most common form of immunodeficiency associated with chromosome 18 abnormalities, however patients with ring chromosome 18 may also be affected by specific antibody deficiency and require immunoglobulin replacement for optimal care. These patients might partially share the same genomic loss as in patients with non-syndromic primary antibody deficiency.Statement of novelty: This report highlights an important teaching point about immune deficiency in a chromosomal anomaly that is not infrequently encountered in pediatric hospitals. Furthermore, our investigations provide more insight into the pathogenesis of immunodeficiency among patients with chromosome 18 abnormalities. - OPEN ACCESSIntroduction: Serum sickness is a type III hypersensitivity reaction. Immune complex deposition activates complement pathways resulting in fever, vasculitic rash, arthritis and lymphadenopathy. Medications are known to trigger serum sickness-like reactions which clinically resemble serum sickness, however, are not thought to involve circulating immune complexes. The full pathophysiology is not clear. Risperidone is an atypical antipsychotic drug commonly used in the paediatric population.Aim: To describe the diagnosis, disease course and outcome of a patient who developed serum sickness-like reaction secondary to risperidone.Methods: Review of patient chart and medical interview in accordance with institutional research ethics board approval.Results: The patient, a 7 year old male with Attention Deficit Hyperactivity Disorder, was started on risperidone 0.25 mg once daily. Within a week the dose was increased to 0.5 mg once daily. During the third week after initiation of medication, the patient developed generalized purpuric, confluent, maculopapular rash. Although the patient did not have any signs and symptoms of a viral illness, he was diagnosed with viral-induced exanthema and continued on risperidone. On day 28, he developed significant, bilateral swelling of upper and lower extremities, facial angioedema, lymphadenopathy, arthralgia and arthritis in ankles, knees, hands and elbows without fever. Investigations showed normal complement C3 and C4 levels. C1 esterase inhibitor, anti-nuclear antibody and urinalysis were normal. Erythrocyte sedimentation rate, C-reactive protein and leukocyte levels were elevated. The diagnosis of serum sickness-like reaction to risperidone was made and the patient subsequently treated with cetirizine, hydrocortisone, and prednisone for 1 week with significant improvement. Skin biopsy was declined by the patients’ parents and therefore was not performed. Provocative oral challenge to risperidone was not considered because of clear suggestive history and ethical consideration.Conclusion: Psychotropic medications are known to cause cutaneous eruptions. Serum sickness-like reactions can happen upon exposure to risperidone. Clinicians should be aware of this potential adverse reaction that can develop weeks after therapy initiation, and be encouraged to discontinue risperidone when the suggestive symptoms emerges.Statement of novelty: We describe a case of serum sickness-like reaction to risperidone in a paediatric patient. To our knowledge, this is the first case of serum sickness-like reaction to risperidone.
- OPEN ACCESSObjective: The objectives of this study are to present a case series of immunodeficient children who underwent a transcervical thymic biopsy and to describe the transcervical approach to the thymus gland.Design: Case series.Setting: Pediatric otolaryngology practice in an academic setting.Patients: Consecutive sample of immunodeficient children (≤18 years old) who underwent thymic biopsies from 1996 to 2019 for the purpose of confirming or excluding profound T cell immunodeficiency.Intervention: Diagnostic transcervical thymic biopsy.Results: A total of 14 patients with atypical combined immunodeficiency underwent the procedure during the study period, with minimal post-operative complication. The thymus was found to be abnormal histologically in 9 children and normal in another 5 patients. In all cases, thymus morphology helped define the extent of the immunodeficiency, resulting in either supporting a decision to perform a bone marrow transplant (8 patients) or avoid this high risk procedure (3 patients).Conclusion: Thymus biopsy is helpful in the characterization of childhood immunodeficiency and provides critical information that affects the medical management. The transcervical approach to the thymus is feasible in children and can be accomplished with minimal morbidity.Statement of novelty: Biopsies of the thymus have assisted in the characterization of new entities of primary immunodeficiency.
- OPEN ACCESSIntroduction: Coronin 1A is part of a family of highly conserved actin regulatory proteins with key roles in T cell homeostasis and T cell receptor signaling. Null mutations in coronin 1A result in severe combined immunodeficiency, whereas hypomorphic mutations have been associated with a somewhat milder immunological phenotype. Nevertheless, all patients described so far have markedly reduced naïve peripheral T cells, impaired T cell responses to mitogens, and limited T cell receptor diversity. Interestingly, despite poor thymic output, thymus architecture appears normal. To date, only 2 cases of hematopoietic stem cell transplantation (HSCT) have been reported in coronin 1A deficiency.Aim: To describe the identification, transplantation course, and long term outcome of a Canadian Inuit patient diagnosed with coronin 1A deficiency.Methods: Patient chart review was performed in accordance with institutional research ethics approval. A combination of immunological investigations and molecular genetic analyses were utilized to identify a novel mutation in the tryptophan-aspartate repeat region of coronin 1A. Based on the patient’s profound T cell dysfunction, the decision was made to proceed with HSCT.Results: The patient presented with a history of recurrent urinary tract infections, otitis media, and developmental delay involving poor axial and peripheral muscle tone. Axillary lymphadenopathy was noted and subsequent thymus biopsy revealed aberrant CD7+ T cell deficiency. Lymphocyte responses to mitogens and T cell receptor excision circle levels were markedly reduced, consistent with the diagnosis of severe combined immunodeficiency. Whole exome sequencing and Sanger confirmation revealed a novel mutation in coronin 1A. HSCT using a HLA-matched unrelated donor resulted in long term engraftment and solid immune reconstitution.Conclusion: Very few patients with coronin 1A deficiency have been described to date, making it difficult to evaluate its natural history and management. Here, we describe the presentation, identification, transplantation, and outcome in our patient.Statement of novelty: We describe the successful hematopoietic stem cell transplantation course and outcome in a patient with a novel mutation in coronin 1A.
- OPEN ACCESSBackground: Patient–physician shared decision making (SDM) can result in better care as well as reduced treatment costs. A better understanding of the factors predicting when physicians implement SDM during the treatment of primary immunodeficiency (PID) could provide insight for making recommendations to improve outcomes and reduce healthcare costs in PID and other long-term chronic conditions.Method: This study made use of grounded theory and was based on the interview responses of 15 immunologists in the United States. It focused on their decision making in the diagnosis and treatment of PID, how they interact with patients, and the circumstances under which they encourage SDM with patients.Results: All invited immunologists took part in the interviews and were included in the study. All but one had 10 or more years of experience in treating PID. The study found that SDM is bounded/limited by “nudging” bias, power balance considerations, and consideration of patient health literacy alignment. Immunologists also reported that they were mainly responsible for coordinating care and for allowing sufficient time for consultations.Conclusion: SDM occurs between the physician and patient throughout the treatment of PID. The study also shows the ways physicians influence SDM by guiding patients through the process.Statement of novelty: Little is known about the factors that influence SDM in the long-term management of chronic diseases. The present study investigated the extent to which immunologists experienced in the treatment of patients with PID include SDM in clinical practice. Findings such of these may be of use when formulating treatment guidelines and improving the effectiveness of long-term management of PID.
- OPEN ACCESS
- Alexandra Langlois,
- Bahar Torabi,
- Marieme Dembele,
- Marylin Desjardins,
- Reza Alizadehfar,
- Moshe Ben-Shohan,
- Isabelle De Bie,
- Ana Santanna,
- Christine McCusker, and
- Bruce Mazer
Background: Gastrointestinal defects and immunodeficiency syndrome (GIDID) is a severe neonatal disorder usually fatal within the first months of life. We report a case presenting with intestinal atresia, combined immunodeficiency, and a novel association with hypothyroidism and cardiac malformations. The immune phenotype was remarkable for agammaglobulinemia, lymphopenia, and mildly decreased lymphocyte proliferation. We present here the unique phenotype as well as studies to determine if the agammaglobulinemia was due to an intrinsic B lymphocyte defect.Methods: Peripheral blood mononuclear cells from the patient and a healthy control were isolated by Ficoll-Hypaque centrifugation and stimulated with anti-CD40, IL-4 and IL-21 for 7 days. Total IgG production was measured by ELISA in the supernatant of the stimulated sample on day 7. Cells were stained for CD19, CD27, IgM, CD11b, CD11c, and CD14.Results: At day 7, supernatant from the patient stimulated cells contained levels of total IgG comparable to the control (755 ng/mL vs. 658 ng/mL, respectively). B cell maturation appeared impaired, as morphologically the patient sample demonstrated fewer B cell clones and cells with dendritic projections.Conclusions: Despite this typical severe clinical picture of GIDID with agammaglobulinemia, IgG production was detected under optimal stimulation for induction of plasma cells. This suggests that there may not be an inherent defect in class switching and antibody production in B cells in this disorder. It is possible that the in vivo physical or cytokine milieu may be defective for optimal B cell function. Further studies assessing the function of the immune cells as well as possible gastrointestinal loss of immunoglobulins are needed in this disease.Statement of novelty: Despite much improvement in understanding the effects of TTC7A mutations in GIDID, the root cause of hypogammaglobulinemia in these patients is still unclear. The work portrayed in this study furthers the current knowledge. It suggests that when appropriately stimulated in vitro, this patient’s B cells were capable of adequate immunoglobulin production. Moreover, to the best of our knowledge, this patient is the first with this genetic defect to be reported with hypothyroidism and cardiac malformations. - OPEN ACCESSBackground: Inherited defects in the function of the purine nucleoside phosphorylase (PNP) enzyme can cause severe T cell immune deficiency and early death from infection, autoimmunity, or malignancy. In addition, more than 50% of patients suffer diverse non-infectious neurological complications. However the cause for the neurological abnormalities are not known.Objectives: Differentiate induced pluripotent stem cells (iPSC) from PNP-deficient patients into neuronal cells to better understand the effects of impaired purine metabolism on neuronal development.Methods: Sendai virus was used to generate pluripotent stem cells from PNP-deficient and healthy control lymphoblastoid cells. Cells were differentiated into neuronal cells through the formation of embryoid bodies.Results: After demonstration of pluripotency, normal karyotype, and retention of the PNP deficiency state, iPSC were differentiated into neuronal cells. PNP-deficient neuronal cells had reduced soma and nuclei size in comparison to cells derived from healthy controls. Spontaneous apoptosis, determined by Caspase-3 expression, was increased in PNP-deficient cells.Conclusions: iPSC from PNP-deficient patients can be differentiated into neuronal cells, thereby providing an important tool to study the effects of impaired purine metabolism on neuronal development and potential treatments.Statement of novelty: We report here the first generation and use of neuronal cells derived from induced pluripotent stem cells to model human PNP deficiency, thereby providing an important tool for better understanding and management of this condition.
- OPEN ACCESS
- Arnon Broides,
- Ronit Gavrieli,
- Jacov Levy,
- Rachel Levy,
- Nurit Hadad,
- Dirk Roos,
- Baruch Wolach, and
- Amit Nahum
Chronic granulomatous disease is a primary immunodeficiency disease caused by a genetic mutation in any of the 5 genes encoding the different components of the Nicotinamide Adenine Dinucleotide Phosphate reduced (NADPH)-Oxidase enzyme complex. Since primary immunodeficiency diseases are considered to be rare diseases, the genetic diagnosis of a certain primary immunodeficiency leads to the reasonable assumption that all patients with the same disease within the same family will have the same genetic mutation. We report 2 patients with chronic granulomatous disease from the same extended consanguineous family who had different genetic causes of their disease. Therefore, it is crucial to obtain a definitive genetic diagnosis of primary immunodeficiency disease even in patients from the same family, where the same genetic diagnosis is presumed to be the cause of the disease.Statement of novelty: Genetic causes of chronic granulomatous disease may be different in patients from the same family. - OPEN ACCESS
Psychosocial issues of the adolescent PI patient and the development of the PI Teen Outreach Program
Background: The effects of disruptions in the lives of the adolescent Primary Immunodeficiency (PI) patient require psychosocial staff involved in their care to find unique approaches to treatment. The demands of living with PI in adolescence complicates this already turbulent life cycle transition. Absence from school due to infections and treatment can lead to social isolation and in turn issues of self-esteem, creating challenges for teenagers with chronic diseases. The importance of maintaining social support with peers and developing a new network of social supports with teens with similar diagnoses is highlighted in the literature as an important factor in helping teens successfully cope with the demands of chronic illness.Methods: To best meet the complex needs of this population, the PI Teen Outreach Program was created in 2010. The goal was to connect teens with PI to one another in an environment that engages them in “normal” activities while providing an opportunity to discuss diagnosis, coping, and the impact of living with PI. The program consists of group teen events that involve an activity for peers to connect followed by a meal for sharing of life experiences. Community peers are invited to assist teens in demystifying their PI disease to their community friends.Results: At the conclusion of each outreach event, teens were given an anonymous evaluation utilizing both Likert scales and qualitative narrative comments. The positive feedback highlights the importance of providing creative and unique programs for this population.Conclusion: A diagnosis of PI can be difficult for teenagers as they cope with the developmental tasks of adolescence alongside a chronic illness. The Teen Outreach Program has been successful in enhancing the psychosocial support and normalizing the experience of teenagers with PI.Statement of novelty: There is a paucity of literature addressing the psychosocial issues that the PI teen population face and any novel programming to address their unique needs. - OPEN ACCESSBackground: Cartilage-hair hypoplasia (CHH), caused by mutations in the ribonuclease mitochondrial RNA-processing (RMRP) gene, is associated with diverse immune abnormalities including combined immune deficiency (CID). Most patients with CHH are managed with supportive measurements, while few have received allogeneic hematopoietic stem cell transplantations (HSCT). The progression of the immune abnormalities and the impact of HSCT in patients with CHH and CID have not been well characterized.Methods: The clinical and laboratory findings of 2 siblings diagnosed in infancy with CHH and CID due to the common 70A>G mutation in RMRP, including the effects of HSCT performed in 1 of them, were compared.Results: Both patients suffered from recurrent respiratory infections at early age with reduced T cells numbers and responses. Patient 1 immune function continued to deteriorate leading to HSCT from an HLA-matched sibling at 4.5 years of age. The patient suffered acute and chronic graft versus host disease of the skin with residual mild joint contractures and scleroderma-like skin changes. Seven years after HSCT patient 1 has normal immune function. Immune evaluations of patient 2 in the first years of life indicated mild improvement. The patient did not have a suitable related HSCT donor and the family elected to continue with supportive care. At 7 years of age, patient 2 is clinically well and thriving with persistent T cell abnormalities.Conclusions: Close monitoring of immune function in early life for patients with CHH and CID as well as the availability of suitable donors assists in determining management, including HSCT.Statement of novelty: The manuscript demonstrates the importance of close monitoring and personalized approach in the management of patients affected by CHH.
- OPEN ACCESSIndividuals with 22q11.2 deletion syndrome (22q11.2DS) have an embryological midline fusion defect, which can result in a syndrome including congenital heart disease, cleft palate, hypoparathyroidism, thymic hypoplasia, immunologic abnormalities, and developmental delay. The majority of patients have a 3 megabase deletion, which contains multiple genes, including the T-box transcription factor (TBX1) gene. Definitive diagnosis is made through fluorescent in situ hybridization (FISH) or chromosomal microarray (CMA). Newborn screening (NBS) for severe combined immune deficiency (SCID) via low T-cell receptor excision circles (TRECs) can also identify this population if thymic output is low. Samples from infants who screen positive undergo further testing, which includes a purine profile and TBX1 deletion analysis. Diagnostic follow-up testing is centre-dependent and may not include more definitive testing for 22q11.2DS by FISH or CMA. We report a case of a newborn with 22q11.2DS, detected by low TRECs on the SCID NBS, with a normal screening TBX1 result, who was subsequently found to have a TBX1 gene deletion on follow-up 22q11.2 FISH and CMA. This case highlights the limitations of the TBX1 screening assay and the importance of performing diagnostic testing with FISH and (or) CMA regardless of the initial TBX1 result. It also emphasizes the need for a standardized follow-up testing algorithm across institutions for newborns who screen positive for SCID.Statement of novelty: To our knowledge, this is the first case to be described in the literature where a newborn with 22q11.2DS with a typical deletion encompassing the TBX1 gene was not identified by initial TBX1 screening, highlighting the limitations of this test as a standalone screening assay.
- OPEN ACCESSHemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory condition believed to be caused by uncontrolled activation of macrophages and histiocytes. HLH may be triggered by infections or associated with malignancy, metabolic disorders and drug toxicity, or alternatively, by a variety of genetic defects. While this disorder has been reported to be associated with a growing number of primary immunodeficiencies, especially those with significant T cell and (or) NK cell dysfunction, it has never been reported in ataxia telangiectasia (AT). AT is characterized by truncal ataxia, dilatation of blood vessels, immunodeficiency and a high predisposition to cancer. Almost all cases of AT have at least 1 or a combination of more than 1 of the following features: low immunoglobulin levels, inability to produce specific antibodies in response to vaccination, T cell lymphopenia and (or) T cell dysfunction. In this report, we describe the first case of a fatal episode of HLH in a patient with AT. The overlapping laboratory anomalies of HLH and lymphoid malignancy poses a challenge for accurate diagnosis, and awareness of the phenomenon by clinicians may result in earlier treatment and resolution of inflammation.Statement of novelty: HLH can affect various types of immunodeficiency but has never been reported in patients with AT. Here, we report the first case of a fatal episode of HLH in a patient with AT.
- OPEN ACCESSBackground: Interleukin-12 Receptor β1 (IL-12Rβ1) deficiency causes susceptibility to weakly virulent atypical mycobacteria and Salmonella. Genotype–phenotype correlations are weak and penetrance is not complete. Most of the culture-recovered Salmonella are with the non typhi types.Case report: We describe an 11 year old male patient with IL-12Rβ1 deficiency. He had an erythematous rash resembling Henoch Schonlein Purpura, and initially presented with slightly elevated CRP. Skin biopsy revealed leukocytoclastic vasculitis. Due to lack of evidence of an active infection, positive ANA, and positive direct Coombs test, an autoimmune lupus-like disease was suspected. In conjunction with rash flares, he showed progressively elevated inflammatory markers, chronic anemia, and hypoalbuminemia. Extensive investigations for an infectious etiology were negative, and without isolation of any pathogens. However, the last of a series of abdominal ultrasound examinations revealed enlarged peritoneal and retroperitoneal lymph-nodes, and biopsy yielded slow-growing bacteria, identified as Salmonella typhi. Prolonged treatment with 2 antimicrobial agents resulted in resolution of skin rash and normalization of laboratory results.Conclusions: We describe an IL-12Rβ1 deficient patient with a progressive inflammatory process with a unique immune dermatological manifestation which was probably triggered by an unexpected pathogen, Salmonella typhi. This patient’s case demonstrates the need for invasive procedures to identify an infectious etiology when routine cultures and serology tests are negative.Statement of novelty: In this case report, we describe a unique presentation of infection with Salmonella typhi in a patient with IL-12Rβ1 deficiency, manifesting with bouts of leucocytoclastic vasculitis. We also report in the same patient, recurrent infection with an unusual pathogen, Kocuria kristinae. Both phenomena have not been reported in such constellation, and we believe this to be a useful and important description that could alert physicians, immunologists, and pediatricians alike to such manifestations. Further, it may help in a rapid and successful diagnosis, therefore benefiting such patients.
