Immunodeficiency and Autoimmune Disorders (42)
Chronic Lymphocytic Leukemia Research (23)
Acute Lymphoblastic Leukemia research (21)
Immunotherapy and Immune Responses (19)
Autoimmune and Inflammatory Disorders Research (18)
Lymphadenopathies can be part of the clinical spectrum of several primary immunodeficiencies, including diseases with immune dysregulation and autoinflammatory disorders, as the clinical expression of benign polyclonal lymphoproliferation, granulomatous disease or lymphoid malignancy. Lymphadenopathy poses a significant diagnostic dilemma when it represents the first sign of a disorder of the immune system, leading to a consequently delayed diagnosis. Additionally, the finding of lymphadenopathy in a patient with diagnosed immunodeficiency raises the question of the differential diagnosis between benign lymphoproliferation and malignancies. Lymphadenopathies are evidenced in 15-20% of the patients with common variable immunodeficiency, while in other antibody deficiencies the prevalence is lower. They are also evidenced in different combined immunodeficiency disorders, including Omenn syndrome, which presents in the first months of life. Interestingly, in the activated phosphoinositide 3-kinase delta syndrome, autoimmune lymphoproliferative syndrome, Epstein-Barr virus (EBV)-related lymphoproliferative disorders and regulatory T cell disorders, lymphadenopathy is one of the leading signs of the entire clinical picture. Among autoinflammatory diseases, the highest prevalence of lymphadenopathies is observed in patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) and hyper-immunoglobulin (Ig)D syndrome. The mechanisms underlying lymphoproliferation in the different disorders of the immune system are multiple and not completely elucidated. The advances in genetic techniques provide the opportunity of identifying new monogenic disorders, allowing genotype-phenotype correlations to be made and to provide adequate follow-up and treatment in the single diseases. In this work, we provide an overview of the most relevant immune disorders associated with lymphadenopathy, focusing on their diagnostic and prognostic implications.
To show the different physician's approaches and the difficulties in the diagnosis and management of the Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) syndrome, and to quantify the impact of the disease on the families and on the healthcare system. Retrospective analysis on 40 patients diagnosed with PFAPA, focusing on the clinical phenotype, the process of diagnosis, and the management of the febrile episodes. The direct and indirect annual economic cost related to PFAPA in the period preceding the diagnosis were also investigated. The median age of patients at disease onset was 1.75 years and the median time to diagnosis was 14.5 months. During the diagnostic process, only 45% of our patients was firstly addressed to rheumatologic consultation, 32.5% to otorinolaryngologist (ORL), and 22.5% to immunologic consultation. Genetic investigations were performed in the 20% of the cohort. Overall population experienced a median of 60 annual days of fever and, during the critical phase, 40% of patients received more than 5 cycles of antibiotic/year. Seventy five percent required laboratory investigations, 18 (45%) needed to access to emergency department and 15 (37.5%) have been hospitalized. The annual mean direct cost was 1659.5 € for each patient, and the estimated mean indirect cost was 5811.6 € for each parent. Despite a benign clinical course, PFAPA syndrome is associated with a significant impact on the patients, their families and the national healthcare system. PFAPA patients require a large number of medical examinations and laboratory or instrumental investigations during the diagnostic approach and often receive inappropriate treatments. Therefore, we suggest the necessity of a greater awareness and knowledge of the disease among primary care physicians and, finally, of the adoption of more specific diagnostic criteria.
Gattorno M, Caorsi R, Meini A, Cattalini M, Federici S , et al.
Pediatrics •
To analyze whether there were clinical differences between genetically positive and negative patients fulfilling periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome criteria and to test the accuracy of the Gaslini diagnostic score for identifying patients with PFAPA syndrome with higher probabilities of carrying relevant mutations in genes associated with periodic fevers. Complete clinical and genetic information was available for 393 children with periodic fever; 82 had positive genetic test results, 75 had incomplete genetic test results, and 236 had negative results for MVK, TNFRSF1A, and MEFV mutations. Current diagnostic criteria for PFAPA syndrome were applied. Of 393 children, 210 satisfied PFAPA syndrome criteria; 43 carried diagnostic mutations (mevalonate kinase deficiency: n = 33; tumor necrosis factor receptor-associated periodic syndrome: n = 3; familial Mediterranean fever: n = 7), 37 displayed low-penetrance mutations or incomplete genotypes, and 130 demonstrated negative genetic testing results. Genetically positive patients had higher frequencies of abdominal pain and diarrhea (P < .001), vomiting (P = .006), and cutaneous rash and arthralgia (P = .01). Genetically negative patients had a higher frequency of exudative pharyngitis (P = .010). Genetically undetermined patients showed the same pattern of symptom frequency as genetically negative patients. The Gaslini diagnostic score was able to identify 91% of genetically positive patients correctly, with a global accuracy of 66%. The Gaslini diagnostic score represents a useful tool to identify patients meeting PFAPA syndrome criteria and at low risk of carrying relevant mutations in genes associated with periodic fevers.