Hematological Indices in Pediatric Diagnosed with Familial Mediterranean Fever

Clinical Criteria and Hematological Indices in Pediatrics Diagnosed with Familial Mediterranean Fever : a Single Center Study in Upper Egypt

To investigate the relationship between the hematological indices and subclinical inflammation in FMF patients during their attack-free period, additionally this study aims to assess the potential of these indices as predictive markers for ongoing inflammation in these patients population at Assuit university hospital of pediatrics.

Study Overview

• Status: Not yet recruiting
• Conditions: Familial Mediterranean Fever (FMF )

Detailed Description

Familial Mediterranean fever (FMF) is the most common hereditary auto inflammatory disease in the world. FMF is caused by gain of function mutations in the MEFV gene, which encodes a protein called pyrin which has regulatory functions on the innate immune system. [1] Mutations interfere with the function of the pyrin domain, initiating an uninterrupted inflammatory cascade [2] Familial Mediterranean fever affects the populations located on the Mediterranean basin. It is virtually limited to Armenians, Turks, Arabs and nonAshkenazi Jews. However, some cases have been described in European countries, including Italy, France, Spain, Portugal and Greece. [3] The clinical presentation of FMF can be variable, likely depending on its genetic heterogeneity and environmental factors. However, the clinical picture is usually very suggestive of the underlying disease. It is typically characterized by recurrent episodes of fever and systemic inflammation with (pleural and peritoneal) serositis and arthritis. Starting in childhood, patients present shortlasting, self-resolving attacks of fever and abdominal, chest, or joint pain with systemic inflammation. Periodicity is not strict and episodes may occur from once a week up to once every three to four months or more in untreated patients. These events are usually very disabling and in clear contrast with complete well-being in attack-free periods [4]. The diagnosis of FMF based on clinical findings is supported by ethnic origin, family history and genetic testing. Several criteria had been developed for the diagnosis of FMF: the most widely used Tel-Hashomer criteria, Most recently, adult and pediatric rheumatology experts have created a new set of classifcation criteria (Eurofever/PRINTO classifcation criteria) [5].

During FMF attacks, many acute phase reactants such as C-reactive protein (CRP), serum amyloid A, fibrinogen, and erythrocyte sedimentation rate (ESR) increase. It is known that a subclinical inflammation continues in FMF patients during the inter attack period and this increases the risk of developing amyloidosis. [6]. Therefore, the use of additional serum markers to evaluate disease activity may provide beneficial advantages for monitoring and preventing further complications. Systemic inflammation also causes changes in the number and composition of circulating blood cells [7] [8]. Neutrophils, lymphocytes and platelets play major roles in systemic inflammation [9]. Neutrophils and platelets secrete proinflammatory cytokines that augment of more neutrophils and platelets [10]. Microparticles released from activated platelets interact with neutrophils through platelet-like lipoxygenase expression and activation of eicosanoid pathway [11]. The platelet count, mean platelet volume (MPV) are the most important indices of platelet function and activation . MPV, a component of routine complete blood count (CBC) tests, is inversely affected by systemic inflammation. MPV levels were shown to be lower in active inflammatory bowel diseases, rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and increased MPV values were reported after treatment. Additionally, the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR), which are easily obtained from differential CBC, have been shown to not only increase in inflammation, but also, be correlated with disease activity and prognosis [12] We discuss the clinical criteria and the association of hematological indices with subclinical inflammation and to evaluate their usability as predictors of ongoing inflammation in FMF patients during their attack-free period

• Study Type: Observational
• Enrollment (Estimated): 93

Contacts and Locations

• Study Contact: Name: khaled mohamed Ahmed Aboelsaud, Bachelor of Medicine; Phone Number: 01111520361; Email: Km5651466@gmail.com
• Study Contact Backup: Name: Naglaa Samy Mohamed Osman, Lecturer of Pediatrics; Phone Number: 01002673103; Email: Naglaaosman84@edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Their clinical presentation and laboratory finding should fulfill the diagnostic criteria as mentioned by Tel Hashomer criteria in pediatrics (≥2 criteria) and Eurofever /PRINTO criteria (≥6 criteria) and confirmed by genetic testing of the most common 12 genetic variants in MEFV gene

Description

Inclusion Criteria:

1. Age at enrollment less than18 years.
2. Both sexes.
3. Diagnosed as familial Mediterranean fever according to Tel-Hashomer criteria in pediatrics and Eurofever /PRINTO criteria

Exclusion Criteria:

1- Patients with acute or chronic active infections. 2- Patients with pre-existing illness as chronic lung, liver or renal diseases. 3- Patients with diabetes mellitus, atherosclerotic vascular disease. 4- Patients with malignancy

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Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
investigate the association of haematological indices with subclinical inflammation	investigate the association of hematological indices with subclinical inflammation and to evaluate their usability as predictors of ongoing inflammation in FMF patients during their attack-free period in Assiut university hospital and to describe the clinical characteristics of patients diagnosed as FMF in Upper Egypt, and to find the most common presenting symptoms.	Baseline

Collaborators and Investigators

• Sponsor: Assiut University

Publications and helpful links

General Publications

• Lancieri M, Bustaffa M, Palmeri S, Prigione I, Penco F, Papa R, Volpi S, Caorsi R, Gattorno M. An Update on Familial Mediterranean Fever. Int J Mol Sci. 2023 May 31;24(11):9584. doi: 10.3390/ijms24119584.
• Assouad E, El Hage S, Safi S, El Kareh A, Mokled E, Salameh P. Familial Mediterranean fever research activity in the Arab world: the need for regional and international collaborations. East Mediterr Health J. 2021 Oct 27;27(10):984-992. doi: 10.26719/emhj.21.036.
• Tufan A, Lachmann HJ. Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review. Turk J Med Sci. 2020 Nov 3;50(SI-2):1591-1610. doi: 10.3906/sag-2008-11.

Study record dates

Study Major Dates

• Study Start (Estimated): October 13, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: September 1, 2024
• First Submitted That Met QC Criteria: September 1, 2024
• First Posted (Actual): September 4, 2024

Study Record Updates

• Last Update Posted (Actual): September 4, 2024
• Last Update Submitted That Met QC Criteria: September 1, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Infections; Genetic Diseases, Inborn; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Skin Diseases, Genetic; Body Temperature Changes; Fever; Brucellosis; Familial Mediterranean Fever; Hereditary Autoinflammatory Diseases
• Other Study ID Numbers: familial Mediterranean fever

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No