Periodic Fever Syndrome: - PowerPoint Presentation

1. Periodic Fever Syndrome:A Literature ReviewSophie JohnsonPA-S2University of South Dakota Physician Assistant Studies ProgramPeriodic fever syndrome is a grouping of rare autoinflammatory conditions. Due to the rarity of these conditions, there is limited data. The purpose of this review was to compile information on etiology, characteristics and diagnosing periodic fever syndromes, as well as evaluating treatment options. Periodic fever syndrome involves autoinflammatory conditions that are alike in the fact that they have recurrent febrile episodes due to an unidentified trigger and without an infectious cause (1). There are 5 types of periodic fever syndrome including PFAPA, FMF, TRAPS, HIDS/MKD and CAPS. The episodes typically recur every 2-8 weeks and symptoms last 1-7 days (3). Sources:PubMedProQuest Research libraryEBSCOhostInterview and patient medical recordsRestrictions:2015-2021 *with a few exceptions*Key words:“Periodic fever syndrome””Recurrent fevers””Diagnosing periodic fevers””HIDS” ”PFAPA” MKD” “CAPS” ”TRAPS” FMF”Diagnosis is usually based on clinical presentation and elimination of other causes. Key findings include distinct sick episodes, with elevated ESR and CRP, separated by symptom free periods with normal biomarkers (2). Genetic testing can be done to confirm specific types. Familial Mediterranean Fever (FMF):Overall, FMF is the most common type of periodic fever syndrome, with higher incidence in Armenian, Turkish, Arab and Sephardic Jewish descent (4). It is caused by a gain of function mutation in MEFV gene, but more than 310 mutations have been found (2). It has an autosomal dominant inheritance pattern with varying penetrance (4). Key symptoms include serositis, gastrointestinal symptoms, peritonitis, arthritis and fevers lasting 1-3 days (5).Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA):Of the periodic fever syndromes, PFAPA is the most common in non-Mediterranean children. It is diagnosed using the Marshall Criteria (6). Key symptoms include arthralgia, headaches, myalgia and fevers lasting 3-7 days (7). Typically resolves in kids by the age of 6 but has been seen in adults (6). Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS)TRAPS is more common in the Caucasian population (8). It has an autosomal dominant inheritance with mutations in the TNFRSF1A gene (3). Symptoms of abdominal pain, myalgia, conjunctivitis, migratory rash, pleuritic chest pain and lymphadenopathy with fevers lasting longer than 5 days, usually start at age 7 (9).Hyperimmunoglobulin D syndrome/ Mevalonate Kinase Periodic Fever Syndrome (HIDS/MKD)HIDS/MKD is a rare type, with recessive inheritance pattern. Diagnosis used to be based on elevated serum IgD levels, but it is neither specific nor sensitive so no longer important (2). It is caused by a loss of function mutation in MVK gene. Symptoms present in infancy. Key symptoms include abdominal pain, diarrhea, aphthous ulcers, maculopapular rash, lymphadenopathy and fevers lasting 3-7 days (10).Cryopyrin-Associated Periodic syndrome (CAPS):There is 3 types with varying severity within CAPS including FCAS, MWS and CINCA/NOMID , from least to most severe(11). These conditions tend to have a seasonal component with worsening episodes in the winter (11). It is caused by a mutation in the NLRP3 gene with an autosomal dominant inheritance pattern (12). Symptoms include urticaria like rash, sensorineural hearing loss, skeletal abnormalities, chronic aseptic meningitis, fevers lasting 1-3 days (11). Treatment:IL-1 inhibitors: Anakinra, Canakinumab, Rilonacept Canakinumab has FDA approval for treatment of FMF, HIDS/MVK and TRAPS. Anakinra has approval for treatment of CAPS (13). ColchicineFDA approved for treatment of FMF (13). Prevents attacks, does not treat current episodeCorticosteroids: Prednisone Single dose at onset of symptomsNSAIDsTNF inhibitors: Adalimumab, Infliximab, EtanerceptTonsillectomyVitamin D supplementationLimited dataThere are multiple approaches to treat periodic fever syndromes. Some treatments focus on prevention and others on symptoms during attack as seen in figure 1. Prednisone and tonsillectomy were most common in the literature. The definition of success also differed between studies. Some studies looked at quality of life, while others looked at what they individually determined to be a complete response including number of episode per year and levels of inflammatory markers. Limitations:Small sample size due to the rarity of the conditions. Majority of information from outside of United StatesFew clinical studiesUnderdiagnosed Periodic fever syndromes are difficult to diagnose and manage. The varying symptoms, unknown origin or type, and lack of specific guidelines for diagnoses or treatment are challenging. Determining type of periodic fever syndrome is important because some treatments are specific to the type. What can we do?Awareness Knowledge of treatment optionsKnow when and where to referAbstractConclusionDiscussionResultsMethods & MaterialsIntroduction1- Graňák, K., Jeseňák, M., Vnučák, M., Skálová, P., Laca, Ľ., Mokáň, M., & Dedinská, I. (2021). Kidney transplantation as a treatment of choice for AA amyloidosis due to periodic fever syndrome. Clinical rheumatology, 40(2), 763–768. https://doi.org/10.1007/s10067-020-05283-2- Lachmann H. J. (2017). Periodic fever syndromes. Best practice & research. Clinical rheumatology, 31(4), 596–609. https://doi.org/10.1016/j.berh.2017.12.0013. Gupta, A., Tripathy, S. K., Phulware, R. H., Arava, S., & Bagri, N. K. (2020). Cryopyrin-associated periodic fever syndrome in children: A case-based review. International journal of rheumatic diseases, 23(2), 262–270. https://doi.org/10.1111/1756-185X.13772 4-  Hausmann J. S. (2019). Targeting cytokines to treat autoinflammatory diseases. Clinical immunology (Orlando, Fla.), 206, 23–32. https://doi.org/10.1016/j.clim.2018.10.0165- Ben-Zvi, I., Kukuy, O., Giat, E., Pras, E., Feld, O., Kivity, S., Perski, O., Bornstein, G., Grossman, C., Harari, G., Lidar, M., & Livneh, A. (2017). Anakinra for Colchicine-Resistant Familial Mediterranean Fever: A Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis & rheumatology (Hoboken, N.J.), 69(4), 854–862. https://doi.org/10.1002/art.399956- Batu E. D. (2019). Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome: main features and an algorithm for clinical practice. Rheumatology international, 39(6), 957–970. https://doi.org/10.1007/s00296-019-04257-0 7- Yildiz, M., Haslak, F., Adrovic, A., Gucuyener, N., Ulkersoy, I., Koker, O., Sahin, S., Unlu, G., Barut, K., & Kasapcopur, O. (2021). Independent risk factors for resolution of periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome within 4 years after the disease onset. Clinical rheumatology, 40(5), 1959–1965. https://doi.org/10.1007/s10067-020-05466-w8- Gaggiano, C., Rigante, D., Sota, J., Grosso, S., & Cantarini, L. (2019). Treatment options for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome in children and adults: a narrative review. Clinical rheumatology, 38(1), 11–17. https://doi.org/10.1007/s10067-018-4361-29- Delaleu, J., Deshayes, S., Rodrigues, F., Savey, L., Rivière, E., Martin Silva, N., Aouba, A., Amselem, S., Rabant, M., Grateau, G., Giurgea, I., & Georgin-Lavialle, S. (2021). Tumor necrosis factor receptor-1 assciated periodic syndrome (TRAPS) related AA amyloidosis: a national case series and systematic review. Rheumatology (Oxford, England), keab252. Advance online publication. https://doi.org/10.1093/rheumatology/keab25210- Hansmann, S., Lainka, E., Horneff, G., Holzinger, D., Rieber, N., Jansson, A. F., Rösen-Wolff, A., Erbis, G., Prelog, M., Brunner, J., Benseler, S. M., & Kuemmerle-Deschner, J. B. (2020). Consensus protocols for the diagnosis and management of the hereditary autoinflammatory syndromes CAPS, TRAPS and MKD/HIDS: a German PRO-KIND initiative. Pediatric rheumatology online journal, 18(1), 17. https://doi.org/10.1186/s12969-020-0409-311- Keddie, S., Parker, T., Lachmann, H. J., & Ginsberg, L. (2018). Cryopyrin-Associated Periodic Fever Syndrome and the Nervous System. Current treatment options in neurology, 20(10), 43. https://doi.org/10.1007/s11940-018-0526-112- Brogan, P. A., Hofer, M., Kuemmerle-Deschner, J. B., Koné-Paut, I., Roesler, J., Kallinich, T., Horneff, G., Calvo Penadés, I., Sevilla-Perez, B., Goffin, L., Lauwerys, B. R., Lachmann, H. J., Uziel, Y., Wei, X., & Laxer, R. M. (2019). Rapid and Sustained Long-Term Efficacy and Safety of Canakinumab in Patients With Cryopyrin-Associated Periodic Syndrome Ages Five Years and Younger. Arthritis & rheumatology (Hoboken, N.J.), 71(11), 1955–1963.13- FDA (2016). FDA approves expanded indications for Ilaris for three rare diseases. U.S. Food and Drug Administration. Retrieved April 30, 2022, from https://www.fda.gov/news-events/press-announcements/fda-approves-expanded-indications-ilaris-three-rare-diseases ReferencesCASE STUDY: A 20-year-old boy first presented with symptoms associated with periodic fever syndrome at the age of 19 months. His symptoms include five-day long episodes of fever, pharyngitis, significant cervical adenopathy, abdominal pain, headache and occasional arthralgias. HIs episodes would recur every 5 weeks. The episodes stopped at age eleven initially, returned at the age of fourteen and stopped again at age nineteen. Patient failed treatment with naproxen during teen years. Next step was short course prednisone (3 days) at onset of symptoms. He went through genetic testing to determine cause. He was negative for the known genetic variants causing periodic fever syndromes, but clinically presents as either PFAPA or HIDS/MKD. Figure 1(2)