Selcan Demir

Familial Mediterranean Fever: Recent Developments in Pathogenesis and New Recommendations for Management

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease (AID) affecting mainly the ethnic groups originating from Mediterranean basin. The disease is characterized by self-limited inflammatory attacks of fever and polyserositis along with elevated acute phase reactants. FMF is inherited autosomal recessively; however, a significant proportion of heterozygotes also express the phenotype. FMF is caused by mutations in the MEFV gene coding for pyrin, which is a component of inflammasome functioning in inflammatory response and production of interleukin-1β (IL-1β). Recent studies have shown that pyrin recognizes bacterial modifications in Rho GTPases, which results in inflammasome activation and increase in IL-1β. Pyrin does not directly recognize Rho modification but probably affected by Rho effector kinase, which is a downstream event in the actin cytoskeleton pathway. Recently, an international group of experts has published the recommendations for the management of FMF. Colchicine is the mainstay of FMF treatment, and its regular use prevents attacks and controls subclinical inflammation in the majority of patients. Furthermore, it decreases the long-term risk of amyloidosis. However, a minority of FMF patients fail to response or tolerate colchicine treatment. Anti-interleukin-1 drugs could be considered in these patients. One should keep in mind the possibility of non-compliance in colchicine-non-responders. Although FMF is a relatively well-described AID and almost 20 years has passed since the discovery of the MEFV gene, there are still a number of unsolved problems about it such as the exact mechanism of the disease, symptomatic heterozygotes and their treatment, and the optimal management of colchicine resistance.

Monogenic Periodic Fever Syndromes: Treatment Options for the Pediatric Patient

Autoinflammatory diseases are disorders of the innate immune system characterized by uncontrolled inflammation. The most commonly encountered autoinflammatory diseases are the hereditary periodic fever syndromes, which present with fever and other features of the skin, serosal membranes, and musculoskeletal system. The main inherited (monogenic) periodic fever syndromes are familial Mediterranean fever (FMF), cryopyrin-associated periodic syndrome (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), and hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD). Recent advances in our understanding of the molecular and pathophysiological basis of autoinflammatory diseases have provided new treatment strategies. Patients with periodic fever syndromes have clearly benefited from anti-interleukin (IL)-1 treatment. Colchicine is still the mainstay of FMF therapy, but IL-1 blockade is also effective if colchicine fails. Early diagnosis and effective treatment can prevent irreversible organ damage. The scope of pathogenic mutations and more targeted therapy for better management of these rare diseases remains to be defined.

Increased psoriasis frequency in patients with familial Mediterranean fever

Abstract Objective: Familial Mediterranean fever (FMF) is a periodic fever syndrome caused by MEFV mutations. FMF may be associated with psoriasis in some cases. The prevalence of psoriasis in the normal Turkish population is 0.42%. We aimed to investigate the prevalence of psoriasis among FMF patients and their relatives. Methods: FMF patients followed at Hacettepe University Adult and Pediatric Rheumatology Departments between January and August 2016 were included. FMF patients/their relatives were accepted to have psoriasis if the diagnosis was made by a dermatologist. Results: A total of 351 FMF patients (177 adults; 174 children) were included. The median (min–max) age of adult and pediatric patients was 35 (19–63) and 10 (2–18) years, respectively. Thirteen (3.7%) FMF patients (11 adults, 2 children) had psoriasis. Psoriasis was more common in adult than pediatric patients (p = 0.02). Psoriasis was present in 22 (12.4%) of adult and 9 (5.2%) of pediatric patients’ relatives (p = 0.023). The frequency of psoriasis in ≥1 relatives of FMF patients was found to be 8.8%. Abdominal pain and fever were significantly higher, and arthralgia, arthritis, pleural chest pain, and pericarditis were significantly less frequent in the pediatric group than in adults (p < 0.05). Conclusion: Psoriasis was more common in FMF patients than in the normal population. Thus, FMF patients should be questioned and carefully examined for psoriasis lesions and psoriasis family history. Prospective multicenter studies may be important to find the incidence of psoriasis in FMF.

Vasculitis: Decade in Review

BACKGROUND In the last decade, we have come to better understand and manage the vasculitides. The classification of vasculitides has been revised. Genome- wide association studies and linkage analyses have been undertaken in hope of better understanding the pathogenesis of vasculitides. Comprehensive genetic studies have highlighted new pathways that may guide us in more targeted therapies. Description of the monogenic forms of vasculitis, such as deficiency of adenosine deaminase type 2 (DADA2), Haploinsufficiency of A20 (HA20), have introduced a new perspective to vasculopathies, and introduced alternative treatments for these diseases. CONCLUSION In this review, the important discoveries in pathogenesis and consensus treatment recommendations from the past decade will be summarized.

Blood group ‘A’ may have a possible modifier effect on familial Mediterranean fever and blood group ‘0’ may be associated with colchicine resistance

Aim/purpose: Our aim was to investigate the association between blood groups and colchicine resistance in familial Mediterranean fever (FMF) patients. METHODS This is a single-center, cross-sectional study. Between January and December 2016, 385 FMF patients were assessed by the Adult and Pediatric Rheumatology outpatient clinics and 297 patients had blood groups (ABO and Rh) results. The patients were grouped into two groups: colchicine-responsive patients (Group CR) and colchicine-unresponsive patients (Group CUR). RESULTS Patients with blood group A had 1.5-fold higher FMF compared with non-A blood group (OR: 1.50 [95% CI: 1.11-1.87]), particularly having a Rh (+) blood group (OR: 1.47 [95% CI: 1.13-1.91]). Furthermore, patients with blood group A had a better response to colchicine treatment than non-A blood group; (OR: 2.21 [95% CI: 1.15-4.27]). Patients with blood group O were prominently associated with colchicine resistance. CONCLUSION ABO blood phenogroups may be used in combination with other risk factors to identify FMF patients and patients at high risk for colchicine resistance.

Pediatric forms of vasculitis

Primary vasculitides that affect children are a challenging and complex group of disorders that may involve any system of the body and lead to significant morbidity and mortality. In recent years, there have been significant advances in the field of childhood vasculitides, including the development of classification criteria and outcome assessment. Although some forms of vasculitis occur in both children and adults, considerable differences exist between childhood and adult vasculitides; we review childhood vasculitides, thus highlighting their differences with the adult forms of the disease. We will also discuss monogenic forms of vasculitis, such as deficiency of adenosine deaminase type 2 (DADA2) and haploinsufficiency of A20 (HA20).

AB1452-HPR Which one has a greater effect on function and the psychosocial status in jia?: disease type or the presence of pain

Background Juvenile idiopathic arthritis (JIA) is a chronic inflammatory childhood disease with symptoms such as joint inflammation, pain and loss of quality of life.1 Types of disease and the presence of pain can impact the child psychosocially, as well as affecting functional activity.2 Objectives The aim of this study is to examine the results of functional and psychosocial status according to the disease type and the presence of pain symptoms in children with JIA. Methods The study included 71 children diagnosed with JIA who applied to the Hacettepe University İhsan Doğramacı Children’s Hospital Rheumatology Department. Following the collection of demographic information, functional status was assessed with the Child Health Assessment Questionnaire (CHAQ) and psychosocial and functional status was assessed with the scale developed in Hacettepe University Faculty of Health Sciences Department of Physiotherapy and Rehabilitation for functional and psychosocial status of children with rheumatism by Edibe Ünal.3 Children were divided into groups according to disease type as oligoarthritis or polyarthritis and the presence or absence of pain. Results Table 1 shows the mean age and numbers of children. There was no difference between the groups according to disease type (p>0,05). On the other hand, comparing scores for the CHAQ total, CHAQ general VAS assessment, functional and psychosocial status according to the presence or absence of pain revealed significant differences (p<0,05).Abstract AB1452HPR – Table 1 Assessment values and comparison statistics Disease Type Pain Oligoarthritis(n=51) Polyarthritis(n=20) p Present(n=21) Absent(n=50) p Age (years) 10,88±3,81 13,50±3,92 0016 11,71±3,77 11,58±4,12 0885 CHAQ Total 0,28±0,29 0,46±0,41 0127 0,51±0,4 0,26±0,27 0012 CHAQ (General VAS) 2,49±2,43 3,93±3 0068 4,46±2,86 2,24±2,3 0002 Function (range 0–30) 4,72±4,85 5,05±6,32 0766 7,85±6,6 3,54±4,02 0004 Psychosocial (range 0–30) 23±5,67 14,5±5,82 0363 16±5,74 12,34±5,4 0012 Function; Psychosocial; Functional and Psychosocial subscales of Ünal’s scale.3 Conclusions We conclude that pain has a greater effect on functional, psychosocial and overall disease assessment in children with JIA when compared to the disease type. Thus, it must be taken into consideration that child’s ability to cope with pain should be improved. References [1] Angelo Ravelli, Alberto Martini. Juvenile idiopathic arthritis.The Lancet2007, 369(9563); 767–778. [2] Laura E Schanberga, John C Lefebvreb, et al. Pain coping and the pain experience in children with juvenile chronic arthritis. Pain1997, 73(2); 181–189. [3] Kısacık Pınar,Ünal Edibe, et al. Juvenil İdiyopatik Artritli Hastalarda Çok Yönlü Bir Değerlendirme Sistemi Oluşturulması Delphi Çalışması. 2016, Annals Of Paediatric Rheumatology Disclosure of Interest None declared