ADA2 deficiency (DADA2) misdiagnosed as systemic onset juvenile idiopathic arthritis in a child carrying a novel compound heterozygous ADA2 mutation: a case report.

Background: The deficiency of adenosine deaminase 2 (DADA2) is caused by an autosomal recessive bi-allelic loss-of-function mutation in the adenosine deaminase 2 (ADA2) gene. DADA2 is a monogenic inherited autoinflammatory disorder characterized by early-onset vasculopathy for which the symptoms range from skin lesions to very severe multiorgan involvement, including life-threatening ischemia and/or hemorrhagic strokes. Owing to the diversity of clinical presentation and the absence of suggestive features, differentiating DADA2 from other inflammatory disorders in the early stages of disease presentation is difficult. Here, we describe the case of a 3-year-old boy who had been misdiagnosed for nearly 2 years before he was definitively diagnosed with DADA2. Case Description: A previously healthy 3-year-old boy was initially diagnosed with systemic onset juvenile idiopathic arthritis (soJIA) owing to recurrent unprovoked fever and elevated acute phase reactants. He developed intractable hypertension during treatment, which his doctor considered an adverse drug reaction. Monogenic inherited autoinflammatory disorders were not suspected until the patient developed intestinal perforation and ensuing recurrent abdominal pain that coincided with fever. Gene sequence analysis revealed a novel compound heterozygous mutation in ADA2. The ADA2 enzyme activity was almost completely lost in the patient. Conclusions: The broad phenotypic spectrum of DADA2 makes early diagnosis challenging. DADA2 should be considered in case of early-onset vasculitis, which is the most common phenotype of DADA2. Early identification and treatment will result in significant improvement of the disease.

X-linked hyper IgM syndrome with severe eosinophilia: a case report and review of the literature.

BACKGROUND: Hyper IgM syndromes (HIGMS) are a group of rare primary immunodeficiency disorders. There are limited reports about HIGMS combined with severe eosinophilia. CASE PRESENTATION: In this report, we described a 2-year-old boy with chronic cough and symptoms of hypoxia. Lung computed tomography (CT) scan showed that diffuse ground-glass changes and eosinophils in peripheral blood increased significantly. Subsequent tests revealed a notable decrease in serum IgG and IgA. The lymphocyte subgroup classification was basically normal. Pneumocystis jirovecii were detected from the bronchoalveolar lavage fluid (BALF) of the patient by metagenomic next-generation sequencing (mNGS). After treatments of caspofungin combined with sulfamethoxazole, intravenous immunoglobulin (IVIG) replacement and anti-inflammatory steroid, the clinical symptoms and pulmonary imaging noticeably improved. The absolute eosinophil count (AEC) also returned to normal range. X-linked hyper IgM syndrome was confirmed by gene test. Two months after the diagnosis, the patient underwent allogeneic stem cell transplantation (HSCT) and has recovered well. CONCLUSIONS: Children with HIGMS are prone to opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). Diffuse interstitial lung disease and hypoglobulinemia in a young child predict the diagnosis of a primary immunodeficiency (PID). mNGS has obvious advantages for obtaining etiological diagnosis of children with PIDs. Severe eosinophilia is rarely reported in this kind of PIDs. Considering literature review and the corresponding reaction to steroid, we proposed that eosinophilia in HIGMS might be related to infections. Steroid therapy can quickly relieve eosinophilia but is easy to rebound if the reduction is too fast. Once the diagnosis of HIGMS is confirmed, the earlier the HSCT, the better the prognosis.

De novo mutation of CYBB gene in a boy presenting as intra-abdominal infection of Burkholderia contaminans: a case report.

BACKGROUND: Chronic granulomatous disease (CGD) is an inborn error of immunity. It is characterized by recurrent bacterial or fungal infections, including infections by Burkholderia species. This is due to respiratory burst dysfunction of phagocytes. Currently, there is no report on Burkholderia contaminans (B. Contaminans) infection in children with CGD. CASE PRESENTATION: We present a previously healthy, 17-month-old Chinese boy infected with B. Contaminans in the intra-abdominal regions. Immunological screening, including assessment of cellular immunity and humoral immunity did not yield conclusive results. The level of nicotinamide adenine dinucleotide phosphatase (NADPH) activity was decreased and whole-exome sequencing identified a de novo mutation in the CYBB gene. CONCLUSIONS: For specific pathogens such as B. Contaminans, immune assessment should be carried out even if there is no positive medical history or specificity in basic immunity screening.

Activated PI3Kδ syndrome 1 mimicking systemic lupus erythematosus and secondary Sjögren's syndrome-like phenotype without recurrent infections: A case report.

Activated phosphoinositide 3-kinase-δ syndrome 1 (APDS1) is a combined immunodeficiency caused by a heterozygous gain-of-function mutation in PIK3CD, encoding the p110δ catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ). APDS1 is characterized by recurrent sinopulmonary infections, leading to airway damage, chronic herpes viremia, lymphoproliferation, and autoimmune and inflammatory diseases. Several cases of systemic lupus erythematosus (SLE) have been reported in APDS1; however, Sjögren's syndrome (SS) or an SS-like phenotype is rarely described in patients with APDS1. In this study, we report a 4-year-old girl with APDS1 who did not experience recurrent sinopulmonary infections and chronic viremia but presented with cytopenia, proteinuria, hypocomplementemia, and positive antinuclear antibodies that met the classification criteria for SLE. Additionally, the patient also mimicked a secondary SS-like phenotype based on recurrent parotitis and labial salivary gland biopsy. The patient achieved remission after treatment with sirolimus and immunosuppressive therapy. This case report enriches the clinical phenotype of APDS1 and provides a reference for the diagnosis and therapy of patients with APDS1.

Percutaneous Transhepatic Papillary Balloon Dilation versus Endoscopic Retrograde Cholangiopancreatography for Common Bile Duct Stones: A Multicenter Prospective Study.

Background Endoscopic retrograde cholangiopancreatography (ERCP) is recommended by major guidelines for the removal of common bile duct (CBD) stones but is technically challenging in patients with low cardiopulmonary reserve and anatomic abnormalities of the upper gastrointestinal (GI) tract. Purpose To compare percutaneous transhepatic papillary balloon dilation (PTPBD) with ERCP for CBD stone removal. Materials and Methods Participants with one to three CBD stones (largest stone ≤30 mm) and without intrahepatic bile duct or gallbladder stones were eligible for this prospective cohort study. PTPBD was recommended in participants with low cardiopulmonary reserve or definitive anatomic abnormalities of the upper GI tract. Otherwise, both procedures were offered without preference. Follow-up, including abdominal CT, was conducted at 1-week and 1-, 3- and 6-month follow-up, and every 6 months thereafter. US and MR cholangiopancreatography were conducted if recurrence could not be confirmed with CT. Technical success rate was the primary outcome. Results A total of 531 participants were analyzed: there were 360 undergoing PTPBD (median age, 76 years; interquartile range [IQR], 64-82 years; 163 men) and 171 undergoing ERCP (median age, 66 years; IQR, 57-74 years; 94 men). The technical success rate was 99% (355 of 360) in the PTPBD group and 98% (167 of 171) in the ERCP group (relative risk, 1.02; P = .12). The incidence of overall complications was 4% (13 of 360) for PTPBD and 8% (13 of 171) for ERCP (relative risk, 0.27; 95% CI: 0.12, 0.61; P < .001). The PTPBD group showed a longer fluoroscopy time and a higher radiation exposure, with adjusted differences of 28.7 minutes (95% CI: 22.2, 35.2) and 384.3 mGy (95% CI: 296.5, 472), respectively. A propensity score-matching analysis (n = 123 per group) indicated that PTPBD had a slightly higher technical success rate and significantly fewer complications. Conclusion When compared with endoscopic retrograde cholangiopancreatography, percutaneous transhepatic papillary balloon dilation has a similar technical success rate and fewer perioperative complications but a higher radiation exposure. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by van Sonnenberg and Mueller in this issue.

[A case of autoimmune lymphoproliferactive syndrome and literature review].

OBJECTIVE: To summarize the clinical characteristics, diagnosis and treatment of a case with autoimmune lymphoproliferative syndrome (ALPS) . METHOD: The patient was diagnosed as autoimmune lymphoproliferactive syndrome (ALPS) after being admitted to the Department of Rheumatism and Immunology of Tianjin Children's Hospital in February 20, 2014. The clinical characteristics, physical examination, laboratory tests, gene tests, and treatment process were analyzed and related literature was reviewed. RESULT: The patient was a 16-month- old boy.Since the first month of life, he started to have repeatedly fever, diarrhea, shortness of breath, lymphadenopathy, hepatosplenomegaly, anemia (HGBmin 50 g/L) and thrombocytopenia (min 35 × 109/L) . But multiple exams showed a normal peripheral blood leukocyte count, hypergammaglobulinemia (IgG 19 800 mg/L, IgA 1 710 mg/L, IgM 2 590 mg/L) and significantly increased serum vitamin B12. Flow cytometric measures showed that CD3⁺ CD4⁻ CD8⁻ T lymphocytes significantly increased ( > 10%) at four times. The count of CD3⁺ TCRαß⁺ CD4⁻ CD8⁻T lymphocytes (double negative T cells; DNTs) >3% twice. The genetic test showed that 309th FAS gene area showed heterozygous mutations, the boy was diagnosed as ALPS. Added examinations of lymphocytes apoptosis induced by FAS was positive. He was treated with prednisone 15 mg once daily and immunomodulator 150 mg three times a day, while in maintaining period with normal levels of hemoglobin and platelet, the dose of prednisone was reduced gradually. Till now, the patient has been treated and observed for 8 months. We retrieved the reports of ALPS in the databases at home and abroad published in recent 10 years, more than 400 cases reported from foreign countries, but there were only 5 domestic cases. Among those, 4 had onset in infancy and 1 at 6-years of age. All the cases presented servere lymphadenopathy and hepatosplenomegaly with anemia (4 of them with hemolytic anemia) and thrombocytopenia. Three cases had a history of frequent infection, one of them had glomerulonephritis. All patient with significant high level of serum immunoglobulin ( > 1.5 times upper limit of normal range), in 3 of them serum vitamin B12 was > 1.5 pg/L (the other 2 cases missed the exam). In 5 cases CD3⁺ CD4⁻ CD8⁻T cells > 10%, and in 2 case DNTs were 8.9% and 15.7% respectively (the other 3 cases missed the exam). Three cases were clearly detected with FAS mutations. All patients were treated with corticosteroid, 2 of them were added with mycophenolate mofetil. The therapy presented effective result in early 1-3 months, but no long-term follow-up reports were available. CONCLUSION: ALPS is a disorder of disrupted lymphocyte homeostasis caused by defective Fas-mediated apoptosis, and it is one of the primary immunodeficiency diseases. The onset of the disease occurs during infancy mainly. Clinical lymphoid hyperplasia and autoimmune phenomena are outstanding signs, which can be associated with frequent infections and allergies. The level of serum vitamin B12 > 1.5 pg/L and the count of CD3⁺ CD4⁻ CD8⁻ T cell show important significance. Exact diagnosis should depend on detecting DNTs and FAS gene.

[Macrophage activation syndrome in children with rheumatic disorders: a retrospective study on 6 patients].

OBJECTIVE: To study the clinical manifestations of rheumatic disorders with macrophage activation syndrome (MAS) in children. METHODS: The authors characterized MAS by carrying out a retrospective study on patients who were identified during the past 12 years in Tianjin Children's Hospital. RESULTS: Six cases (4 females, 2 males) were studied. Four had typical systemic onset juvenile idiopathic arthritis (SOJIA), two had systemic lupus erythematosus (SLE) with lupus nephritis. Clinical manifestations at diagnosis, which occurred in the lower activity state of these primary diseases, included high spiking fever (in 5 cases) or high fever (in 1), hepatosplenomegaly (in 6), lymphadenopathy (in 6), profound decrease of all 3 blood cell lines (in 6), significant injury of liver (in 6), diseminated intravascular coagulation (DIC)-like picture (in 2), and central nervous system dysfunction (in 3). Hypofibrinogenemia, elevated liver enzymes and hypertriglyceridemia were found consistently. The phagocytic histiocytes with plasmacytosis were found in 3 bone marrow smears (not done in others). MAS was presumed to have been precipitated by viral infections in 3 patients, two had evidences for herpes simplex virus infection and one for hepatitis A virus infection. The treatment regimen was tailored to each patient, as the clinical course was variable. CONCLUSIONS: MAS may not only be most frequently seen in children with SOJIA, but also in those with other rheumatic diseases, and may be a syndrome that is more common than previously thought. Infection may be main trigger factor for MAS. The immunoapheresis combined with immunochemotherapy may be optimal for severe injury of the liver in patients with MAS.