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Mastocytosis is characterized by abnormal clonal mast cell proliferation. Given the paucity of data in patients with mastocytosis, it is crucial to assess the safety of COVID-19 vaccines in this population. We aimed to assess the risk of allergic reactions and the effect of COVID-19 infection among patients with mastocytosis. Participants were recruited from Canada and Israel between December 2021 and May 2022. Consenting participants were administered standardized questionnaires querying whether they were infected with COVID-19, if they received the first and second dose vaccines, and post-vaccination side effects including allergic reactions (urticaria/angioedema, current rash flaring, need for updosing medications, or respiratory symptoms) and common side effects including injection site reaction (ISR) and flu-like symptoms. Forty participants with mastocytosis were administered a standardized questionnaire (median age = 9, 59% male). Amongst all participants, 16 (39%) reported COVID-19 infection and most (75%) reported flu-like symptoms, 3 (19%) were asymptomatic, 1 suffered from shortness of breath/chest pain and 1 from facial flushing. Of the 25 participants who were eligible for vaccination (≥ 5 years old), 80% received a first-dose vaccine and 68% received a second-dose vaccine. Of those who received the first-dose vaccine, most (60%) remained asymptomatic, 20% developed flu-like symptoms, 20% had an ISR, and 1 patient had an allergic reaction (urticaria and swelling). Of those who received the second-dose vaccine, most (53%) were asymptomatic, and 1 had an allergic reaction. No significant difference was found between side effects of both vaccine doses. No reactions fulfilled the criteria for anaphylaxis in either dose. This study reveals that among patients with mastocytosis, COVID-19 vaccine and infection were well-tolerated in the majority of cases. [ABSTRACT FROM AUTHOR]

Objective: Juvenile psoriatic arthritis (JPsA) is a severe inflammatory arthritis, which is associated with psoriasis in most cases. While there are few validated screening tools for diagnosis of arthritis for adult patients with psoriasis, those screening tools were never evaluated in children. The aims of this study were to evaluate two screening tools among pediatric patients with psoriasis. Methods: Thirty-nine patients with the diagnosis of psoriasis completed two screening questionnaires: The Psoriasis Epidemiology Screening Tool (PEST) questionnaire and the new Early Arthritis for Psoriatic Patients (EARP) questionnaire. All patients were evaluated by a rheumatologist for the diagnosis of JPsA, and the accuracy of the two questionnaires was compared. Results: The 4/39 (10.1%) patients diagnosed with JPsA had a PEST questionnaire score of ≥ 3, compared to a median PEST score of the patients without the diagnosis of JPsA of 0 (0–2). Thus, both the sensitivity and specificity of the PEST in diagnosing JPsA were 100%. For the EARP questionnaire, 8/39 patients had a screening questionnaire score of ≥ 3, suggestive of JPsA, four were true positive, and four false positive. Thus, the sensitivity and specificity of EARP in diagnosing JPsA were 100% and 89%, respectively. Conclusion: Both the PEST and EARP questionnaires were easy to use and had high sensitivity for the diagnosis of JPsA in the pediatric population with psoriasis. The PEST questionnaire had a higher specificity than the EARP. Key Points: • EARP and PEST are good screening tools for diagnosis of arthritis in pediatric population with psoriasis. [ABSTRACT FROM AUTHOR]

Aim: We aimed to describe the experience of a large single-center cohort for the clinical, radiological, and genetic characteristics, as well as to determine the efficacy of different anti-epileptic strategies in children and adults with tuberous sclerosis complex (TSC). Methods: We carried out a historical cohort study on 91 TSC patients treated in a single center between 2008 and 2018. Results: Our cohort comprised 46 males and 45 females, with a median age of 15.6 years at the last follow-up. Mean follow-up time was 2.5 ± 0.75–5.5 years (range 0–9.5 years). Of those tested, a disease-causing mutation was identified in 90% of patients, 53% in TSC2, and 37% in TSC1. Epilepsy prevalence was similar among TSC1 and TSC2 mutated patients. The most common radiological finding were cortical tubers in 95% of patients, while subependymal giant cell astrocytoma (SEGA) were detected in 36% of patients. Notably, infantile spasms (IS) were diagnosed in 29%, with SEGA representing the only finding significantly different in prevalence between those with and without IS (62% vs. 28%, respectively, p = 0.009). Lastly, we did not find any difference in efficacy between three anti-epileptic treatments: Vagus nerve stimulation (VNS), CBD-based products, and the ketogenic diet, all showing approximately 30%–40% response rates. Significance: Altogether, we provide a comprehensive description of our experience in treating TSC, which could serve to expand current knowledge of the disease and its treatments. [ABSTRACT FROM AUTHOR]

MALT1 (mucosa-associated lymphoid tissue lymphoma-translocation gene 1) is an intracellular signaling protein that activates NFκB and is crucial for both the adaptive and innate immune responses. Only 6 patients with immune deficiencies secondary to inherited mutations in the MALT1 gene have been described. Purpose: To provide clinical and immunological insights from 2 patients diagnosed with MALT1 immunodeficiency syndrome due to a novel MALT1 mutation. Methods: Two cousins with suspected combined immunodeficiency underwent immunological and genetic work-up, including lymphocyte phenotyping, lymphocyte activation by mitogen stimulation, and next-generation sequencing (NGS) of T cell receptor gamma chain (TRG) repertoire. Whole exome sequencing was performed to identify the underlying genetic defect. Results: Clinical findings included recurrent infections, failure to thrive, lymphadenopathy, dermatitis, and autoimmunity. Immune work-up revealed lymphocytosis, low to normal levels of immunoglobulins, absence of regulatory T cells, and low Th17 cells. A normal proliferative response was induced by phytohemagglutinin and IL-2 but was diminished with anti-CD3. TRG repertoire was diverse with a clonal expansion pattern. Genetic analysis identified a novel autosomal recessive homozygous c.1799T>A; p. I600N missense mutation in MALT1. MALT1 protein expression was markedly reduced, and in vitro IL-2 production and NFκB signaling pathway were significantly impaired. Conclusions: Two patients harboring a novel MALT1 mutation presented with signs of immune deficiency and dysregulation and were found to have an abnormal T cell receptor repertoire. These findings reinforce the link between MALT1 deficiency and combined immunodeficiency. Early diagnosis is crucial, and curative treatment by hematopoietic stem cell transplantation may be warranted. [ABSTRACT FROM AUTHOR]

Generalized lymphatic anomaly (GLA or lymphangiomatosis) is a rare disease characterized by a diffuse proliferation of lymphatic vessels in skin and internal organs. It often leads to progressive respiratory failure and death, but its etiology is unknown. Here, we isolated lymphangiomatosis endothelial cells from GLA tissue. These cells were characterized by high proliferation and survival rates, but displayed impaired capacities for migration and tube formation. We employed whole exome sequencing to search for disease-causing genes and identified a somatic mutation in NRAS. We used mouse and zebrafish model systems to initially evaluate the role of this mutation in the development of the lymphatic system, and we studied the effect of drugs blocking the downstream effectors, mTOR and ERK, on this disease. [ABSTRACT FROM AUTHOR]

Background: Infantile hemangioma (IH) is a most common tumor of infancy. Using infantile hemangioma-derived stem cells (HemSCs), we recently demonstrated that corticosteroids suppress the expression of VEGF-A, monocyte chemoattractant protein-1 (MCP-1), urokinase plasminogen activator receptor (uPAR), and interleukin-6 (IL-6); each of these are known targets of the transcription factor nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB). In the present study, we examined the expression of these NF-κB target genes in IH tissue specimens and the effect of NF-κB regulation on the expression of pro-angiogenic cytokines, and in particular VEGF-A, in HemSCs. Materials and methods: RNA extracted from IH tissue and hemangioma-derived stem cells (HemSCs) was used to analyze NF-κB target gene expression by reverse transcription-quantitative PCR (RT-qPCR). The effects of NF-κB blockade were examined in HemSCs. Immunostaining, immunoblotting and ELISA were used to assess protein expression. Results: MCP-1, uPAR, and IL-6 were found to be differentially expressed in proliferating versus involuting IH. Corticosteroids suppressed NF-κB activity of HemSCs. Velcade (Bortezomib), a proteosome inhibitor that can indirectly inhibit NF-κB, impaired HemSCs viability and expression of pro-angiogenic factors. Furthermore, specific inhibition of NF-κB resulted in suppression of VEGF-A. Conclusions: We demonstrate expression of NF-κB target genes in proliferating IH. In addition, we show that the expression of several pro-angiogenic factors in HemSCs, and in particular VEGF-A, is regulated by NF-B activity. [ABSTRACT FROM AUTHOR]