Successful management of colchicine resistant familial Mediterranean fever patients with a standardized canakinumab treatment protocol: a case series and literature review.

Familial Mediterranean fever (FMF) is the most common monogenic auto-inflammatory disease characterized by recurrent attacks of fever and serositis. Although colchicine is the first line treatment in FMF, 5-10% of patients do not respond to colchicine. Canakinumab, an anti-IL-1ß monoclonal antibody, has been reported to be effective and safe in colchicine-resistant FMF patients, but the adequate duration and interval of treatment is still a matter of debate. Aim of this study was to evaluate the success of the standardized treatment protocol for canakinumab applied in our Pediatric Rheumatology Department in colchicine-resistant FMF cases with a review of the literature. Nine patients included in this study had indications for canakinumab use as colchicine resistance and recurrent corticosteroid need for pleural/pericardial effusions. Canakinumab was administered monthly for 6 months (initial treatment), bimonthly for 6 months (maintenance treatment), then treatment was discontinued. For the patients who developed a new attack after one-year treatment period, canakinumab was readministered with 3-month intervals (continuation treatment). The mean follow-up time beginning from the first canakinumab injection was 24.3 ± 10.2 (6-33) months. None of the patients had an attack during the first-year treatment. Four of the patients developed an attack 9.0 ± 2.9 (6-12) months after discontinuation of treatment and switched to the continuation treatment period, with no more attacks. We suggest that this standard protocol may be used successfully in colchicine-resistant FMF patients.

Evaluation of the Impact of Environmental Changes on Asthma Control in Children, Access to Health Care, and Treatment Adherence in Early COVID-19 Lockdown.

OBJECTIVE: During the coronavirus disease 2019 pandemic, lockdown measures and difficulties in accessing healthcare have impacted asthma management in children. This study aimed to determine the evaluation of the impact of environmental changes on asthma control in children, access to health care, and treatment adherence in early coronavirus disease 2019 lockdown. MATERIALS AND METHODS: The study included children with asthma aged 6-11 years. A survey form was administered to the patients who visited the pediatric allergy outpatient clinic between June 1 and 30, 2020. The survey acquired demographic information about the children and their families as well as information about their asthma symptoms, how they reached healthcare services, and adherence. The childhood asthma control test was administered. The P values <.05 were considered significant. RESULTS: The study included a total of 123 children (female/male : 48/75) with a mean age of 8.4 ± 1.9 years. According to the mothers' self-report, it was found that 78% of the patients were not able to follow-up routinely, 19.5% were non-adherence to treatment, and 16.2% were poorly controlled asthma. It was found that, based on childhood asthma control test scores, asthma control was better during the pandemic lockdown period (P = .001). Asthma symptoms were better in 41.5% of the patients compared to the previous months and in 53.7% compared to the same period last year. CONCLUSION: Our study found that the children's asthma was controlled although most of them did not have their follow-up visits, and poorly controlled asthma was higher in older children in early coronavirus disease 2019 lockdown.

Anxiety Levels and Changes in Health and Hygiene Behaviors in Mothers of Children with Asthma in Early COVID-19 Lockdown in Turkey.

Objective: The restrictions imposed by the coronavirus disease 2019 (COVID-19) pandemic have caused significant changes in people's lives. This study aimed to investigate anxiety levels and changes in health and hygiene behaviors in mothers of children with asthma in early COVID-19 lockdown in Turkey. Materials and Methods: This study was a cross-sectional survey conducted on children with asthma, 6 to 11 years of age, between June 1 and 30, 2020, in Turkey. A sociodemographic data form, health and hygiene behavior form, childhood asthma control test, and state-trait anxiety inventory were administered to the mothers of the children. Results: The asthma group included 123 children (Female: 39.0%) and median age, interquartile range (IQR) [minimum-maximum]: 8.0 (6) [6-12] years; the control group included 88 children (Female: 47.7%) median age, IQR [minimum-maximum]: 8.0 (7) [5-12] years. Increased hygiene behaviors and high compliance with social isolation measures were recorded in the early lockdown, with no difference between the groups. Before the pandemic, the most frequently used cleaning products were general-purpose cleaners. During the early lockdown, however, the most frequently used product was disinfectants and was similar in both groups. In both groups, the rate of using nutritional supplements increased during the pandemic period, but the rate was higher in children with asthma both before and during the early lockdown (P < 0.001). The anxiety levels of the mothers in asthma and control groups were similar. Conclusion: This study is the first in Turkey demonstrating that, in mothers of children with asthma, lifestyle changes related to health and hygiene and anxiety levels are similar to those of other children and their mothers during the early lockdown period of COVID-19 pandemic.

Cut-Off Values of Specific IgE and Skin Prick Test to Predict Oral Food Challenge Positivity in Children with Cow's Milk Allergy.

OBJECTIVE: The cut-off values for the skin prick test diameters and cow's milk-specific IgE measurements are used to predict the result of the oral food challenge test for the diagnosis of cow's milk allergy. This study aimed to determine the diagnostic values of skin prick test and cow's milk-specific IgE according to age groups and compare the diagnostic powers of these 2 methods. MATERIALS AND METHODS: In total, 153 children who had a preliminary diagnosis of cow's milk allergy were evaluated. Group A (n = 90) consisted of cow's milk allergy patients whose diagnosis was confirmed by a positive oral food challenge or a history of anaphylaxis. Group B (n = 63) was composed of patients with a negative oral food challenge. The demographic, clinical, and laboratory findings of 2 groups were compared. RESULTS: The cut-off points for cow's milk-specific IgE and cow's milk-skin prick test were determined as >2.12 kUA/L and >5 mm, respectively. The area under the curve was 0.844 for cow's milk-skin prick test (sensitivity 73%, specificity 84%) and 0.745 for cow's milk-specific IgE (sensitivity 67%, specificity 86%). The diagnostic power of skin prick test was determined to be higher when compared to cow's milk-specific IgE (P = .02). According to the predicted probability curves, decision points for cow's milk-specific IgE and cow's milk-skin prick test with 95% probability were determined as follows, respectively: for ≤24 months: 22 kUA/L, 11.3 mm; for >24 months: 44.1 kUA/, 15.1 mm. The lowest cut-off value with a positive predictive value of 95% and a specificity of 96% was found in patients 3.3 kUA/L) Conclusion: The use of high probability diagnostic values of communities for specific IgE and skin prick test along with a significant clinical history may provide accurate and rapid diagnosis of cow's milk allergy and facilitate patient follow-up.

Deficiency of Interleukin-1 Receptor Antagonist: A Case with Late Onset Severe Inflammatory Arthritis, Nail Psoriasis with Onychomycosis and Well Responsive to Adalimumab Therapy.

DIRA (deficiency of the IL-1Ra) is a rare condition that usually presents in the neonatal period. Patients with DIRA present with systemic inflammation, respiratory distress, joint swelling, pustular rash, multifocal osteomyelitis, and periostitis. Previously, we reported a patient with a novel mutation in IL1RN with a healthy neonatal period, a late-onset of pustular dermatosis, inflammatory arthritis, and excellent response to canakinumab treatment. Herein, we are presenting a new case of late-onset DIRA syndrome, carrying a different mutation and showing different clinical findings. This patient is the first one in the literature with the inflammatory arthritis, nail psoriasis, and onychomycosis and with her remarkable response to monoclonal antibodies. The case responded well and fully recovered after treatment with adalimumab, but not with canakinumab. The DIRA disease can lead to death from multiple organ failures and if recognized early, the treatment with replacement of the deficient protein with biologic agents induces rapid and complete remission. Therefore, clinical symptoms should be learned exactly by the pediatricians, pediatric rheumatologists, and immunologists; and molecular analysis targeting this defect must be performed as early as possible.

Two male siblings with a novel LRBA mutation presenting with different findings of IPEX syndrome.

INTRODUCTION: LPS-responsive beige-like anchor (LRBA) protein deficiency is a disease of immune dysregulation with autoimmunity affecting various systems. CASE PRESENTATION: Two male siblings with a novel LRBA mutation had different primary findings at admission: the younger sibling had chronic early-onset diarrhoea and the elder one had autoimmune haemolytic anaemia. During long-term follow-up for IPEX phenotype, both developed hypogammaglobulinaemia, enteropathy and lung involvement. The patients partially responded to immunosuppressive therapies. A homozygous c.2496C>A, p.Cys832Ter (p.C832*) mutation in the LRBA gene causing a premature stop codon was detected. After molecular diagnosis, abatacept, as a target-specific molecule, was used with promising results. CONCLUSION: LRBA deficiency is a recently defined defect, with variable presentations in different patients; a single, definitive treatment option is thus not yet available.

Necrotizing Liver Granuloma/Abscess and Constrictive Aspergillosis Pericarditis with Central Nervous System Involvement: Different Remarkable Phenotypes in Different Chronic Granulomatous Disease Genotypes.

Chronic granulomatous disease (CGD) is a primary immune deficiency causing predisposition to infections with specific microorganisms, Aspergillus species and Staphylococcus aureus being the most common ones. A 16-year-old boy with a mutation in CYBB gene coding gp91phox protein (X-linked disease) developed a liver abscess due to Staphylococcus aureus. In addition to medical therapy, surgical treatment was necessary for the management of the disease. A 30-month-old girl with an autosomal recessive form of chronic granulomatous disease (CYBA gene mutation affecting p22phox protein) had invasive aspergillosis causing pericarditis, pulmonary abscess, and central nervous system involvement. The devastating course of disease regardless of the mutation emphasizes the importance of early diagnosis and intervention of hematopoietic stem cell transplantation as soon as possible in children with CGD.

Gain-of-Function Mutations in STAT1: A Recently Defined Cause for Chronic Mucocutaneous Candidiasis Disease Mimicking Combined Immunodeficiencies.

Chronic Mucocutaneous Candidiasis (CMC) is the chronic, recurrent, noninvasive Candida infections of the skin, mucous membranes, and nails. A 26-month-old girl was admitted with the complaints of recurrent oral Candidiasis, diarrhea, and respiratory infections. Candida albicans grew in oral mucosa swab. CMV and EBV DNA titers were elevated. She had hypergammaglobulinemia; IgE level, percentages of lymphocyte subgroups, and in vitro T-cell proliferation responses were normal. She had parenchymal nodules within the lungs and a calcific nodule in the liver. Chronic-recurrent infections with different pathogens leading to significant morbidity suggested combined immunodeficiency, CMC, or Mendelian susceptibility to mycobacterial diseases. Genetic analysis revealed a predefined heterozygous gain-of-function mutation (GOF) (c.1154 C>T, p.Thr385Met) in the gene coding STAT1 molecule. Hematopoietic stem cell transplantation (HSCT) was planned because of severe recurring infections. Patients with STAT1 GOF mutations may exhibit diverse phenotypes including infectious and noninfectious findings. HSCT should be considered as an early treatment option before permanent organ damage leading to morbidity and mortality develops. This case is presented to prompt clinicians to consider STAT1 GOF mutations in the differential diagnosis of patients with chronic Candidiasis and recurrent infections with multiple organisms, since these mutations are responsible for nearly half of CMC cases reported.