Hafize Emine Sönmez

Familial Mediterranean fever: current perspectives

Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disease, and it is characterized by recurrent attacks of fever and polyserositis. The disease is associated with mutations in the MEFV gene encoding pyrin, which causes exaggerated inflammatory response through uncontrolled production of interleukin 1. The major long-term complication of FMF is amyloidosis. Colchicine remains the principle therapy, and the aim of treatment is to prevent acute attacks and the consequences of chronic inflammation. With the evolution in the concepts about the etiopathogenesis and genetics of the disease, we have understood that FMF is more complicated than an ordinary autosomal recessive monogenic disorder. Recently, recommendation sets have been generated for interpretation of genetic testing and genetic diagnosis of FMF. Here, we have reviewed the current perspectives in FMF in light of recent recommendations.

Tocilizumab treatment in childhood Takayasu arteritis: Case series of four patients and systematic review of the literature

OBJECTIVE Our aim was to describe our experience with tocilizumab (interleukin 6 receptor antagonist) treatment in children with Takayasu arteritis and to review previous studies regarding tocilizumab use in Takayasu arteritis patients. PATIENTS AND METHODS We reviewed the charts of all pediatric Takayasu arteritis patients followed up between 2000 and 2015 in Department of Pediatric Rheumatology in Hacettepe University, Ankara, Turkey, and we present the patients who were treated with tocilizumab. We screened PubMed and MEDLINE for articles involving Takayasu arteritis patients treated with tocilizumab. RESULTS We have followed four pediatric Takayasu arteritis patients who received tocilizumab. The median duration of immunosuppressive treatment before tocilizumab onset was 16 (1-60) months. The median duration of tocilizumab treatment was 9.5 (7-13) months. One of our patients received tocilizumab as a first line immunosuppressive treatment directly after methylprednisolone. Others were resistant to their initial immunosuppressive treatment (cyclophosphamide, methotrexate, or azathioprine). All achieved complete response to tocilizumab at the third month of treatment. None of the patients reported any adverse events during the follow-up. In literature review, we identified 19 articles describing 75 Takayasu arteritis patients treated with tocilizumab. Eight of these received tocilizumab before the age of 18 years. Tocilizumab was the first line immunosuppressive treatment in six patients (five adults and one child). CONCLUSION Our small series suggests that tocilizumab may be a promising alternative for Takayasu arteritis treatment. Long-term controlled studies are warranted to provide better evidence for tocilizumab treatment in childhood Takayasu arteritis.

A clinical update on inflammasomopathies

Inflammasomes are important elements of the innate immune defense. The most common autoinflammatory syndromes, as well a number of rare ones, are due to hereditary defects in the inflammasomes, hence are called inflammasomopathies. The recent clinical advances in these diseases will be reviewed, with special emphasis on reflecting the international collaborative work in the field. Recent recommendations for familial Mediterranean fever, cryopyrin-associated periodic syndromes and hyper-IgD syndrome/mevalonate kinase deficiency will be presented and diagnostics tests, treatment alternatives and follow-up recommendations will be summarized. The other rare inflammasomopathies will be briefly discussed based on clinical features; these diseases are pyogenic arthritis, pyoderma gangrenosum and acne, NLRC4-related macrophage-activation syndrome of enterocolitis, mutations in NLRP12 that cause hereditary periodic fever syndromes (familial cold inflammatory syndrome 2) and NLRP1-associated autoinflammation with arthritis and dyskeratosis.

Current Research in Outcome Measures for Pediatric Rheumatic and Autoinflammatory Diseases

A rational management of children and adolescents with rheumatic and autoinflammatory diseases requires the regular assessment of the level of disease activity and of child health and well-being through the use of well-validated outcome measures. Ideally, such instruments should be simple and feasible and easily applicable in standard clinical practice. In recent years, a number of novel outcome measures have been developed and validated for use in pediatric patients with rheumatic and autoinflammatory illnesses. Furthermore, there has been an increased focus on the appraisal of child and parent perception of the disease impact. The new tools have markedly enlarged the spectrum of disorders and health domains that can be assessed in a standardized way. This progress will help to enhance the reliability of research studies and clinical trials. The aim of the present review is to provide an update of the recent advances in this field of research.

Comparing polyarteritis nodosa in children and adults: a single center study

Polyarteritis nodosa (PAN) is a necrotizing vasculitis of medium/small arteries. We aimed to examine the characteristics of adult‐ and childhood‐onset PAN.

Acceptability and Practicality of the Turkish Translation of Pediatric Gait Arm Legs and Spine in Turkish Children

Background The pediatric Gait, Arms, Leg, and Spine (pGALS) is a practical questionnaire for musculoskeletal (MSK) system evaluation in school-age children. Objective The aim of this study was to evaluate the acceptability/practicality of pGALS Turkish translation in Turkey (cross-sectional study). Methods The Turkish translation of pGALS was administered to children (4–18 years) who attended to the Pediatric Emergency Department of Hacettepe University, Ankara, Turkey, and the outpatient clinic of the Physical Therapy and Rehabilitation Department of Marmara University, Istanbul, Turkey, during 1 month in 2016. The demographics, complaints, final diagnoses, and pGALS parameters were noted. The acceptability of pGALS was evaluated using visual analog scale. Results Ninety-five patients (median age, 108 months; male/female, 1.1) were enrolled. Sixteen patients (16.8%) had MSK diagnosis, whereas 79 (83.2%) had non-MSK diagnoses. Musculoskeletal diagnoses were as follows: scoliosis (n = 4), metatarsus adductus (n = 4), soft tissue injury (n = 3), lumber disk herniation (n = 2), muscle spasm (n = 1), Achilles tendinitis (n = 1), and tibia torsion (n = 1). The sensitivity was 64.7%, and specificity was 89.7% for positive response to 1 or more pGALS screening questions to detect abnormal pGALS. The most sensitive question was pain question. The most common abnormal pGALS components were spine and posture. The sensitivity and specificity of pGALS for detecting MSK diagnosis were 93.7% and 97.4%, respectively. The median duration of pGALS examination was 4 minutes. Most patients/parents found the duration acceptable (94.7%/97.9%, respectively) and reported that pGALS caused little/no discomfort (97.9%/96.8%, respectively). Conclusion This is the first study showing the Turkish version of pGALS as a valid, acceptable, and practical screening test in Turkey.

Hypomorphic RAG1 defect in a child presented with pulmonary hemorrhage and digital necrosis

• In the patients with atypical presentations of vasculitis, suspicion of monogenic disorders may avoid delays in diagnosis and treatment.

Concurrence of juvenile idiopathic arthritis and primary demyelinating disease in a young child

CASE REPORT The association of juvenile idiopathic arthritis (JIA) and primary demyelinating disease of central nervous system (CNS) in the same patient is rare. Here we present a 10-year-old girl formerly diagnosed with JIA who presented with acute total vision loss. Magnetic resonance imaging of the brain and spinal cord showed bilateral optic neuritis and T2 hyperintense lesions in the brain, cerebellum and cervical spinal cord, some of them gadolinium-enhancing. Oligoclonal bands were present in the cerebrospinal fluid. Visual evoked potentials were prolonged. Aquaporin-4 antibodies were negative. The patient was treated with methylprednisolone 30 mg/kg daily for five days, resulting in improvement in vision and gait. This first demyelinating event in this patient with JIA with clinical and paraclinical features meeting the 2017 MS diagnostic criteria supports a possible predisposition to autoimmune disorders. CONCLUSION The concurrence of JIA and multiple sclerosis (MS) has been reported in only two adult cases and not in the pediatric population. While JIA and MS are two distinct chronic inflammatory diseases, immunogenetic predisposition and common environmental triggers might be involved.

Characteristics of Patients Referred to the Pediatric Rheumatology Polyclinic with Anti-Nuclear Antibody (Ana) Positivity

Objective: Anti-nuclear antibodies (ANA) develop against the structures found in the cell nucleus. These antibodies can be positive in the autoimmune disorders, but they can be also detected in healthy people. The objective of our study was to determine the definitive diagnosis of the patients referred to our clinic due to the ANA positivity and find out whether they develop rheumatologic disorders during the clinical follow-up. Material and Methods: We have reviewed the medical files of children who were referred to the pediatric rheumatology department between 2014 and 2016 with ANA positivity. Results: 43 subjects were enrolled in the study. The complaints of the referred patients at first presentation were as follows: joint symptoms in 19 patients (44.2%), mucocutaneous symptoms in 13 patients (30.2%), hematological findings in 6 patients (14%), neurological symptoms in 3 patients (7%), and Raynaud’s phenomenon in 2 patients (4.6%). 34 patients (79%) had a positive ANA titer ≥ 1/160. The ANA titer level was below 1/160 in 9 patients (21%). 23 patients (53.4%) were diagnosed with a rheumatologic disease, while 20 patients did not have any rheumatologic disorder. There was no significant difference between the ANA-positive (n=34) and ANA-negative (n=9) patients with regards to the clinical and laboratory characteristics. The comparison of the patients with and without a rheumatologic disorder revealed that the presence of auto-antibodies was more common and acute phase reactant levels were higher in the disease group for arthralgia, arthritis and Raynaud’s phenomenon. Conclusion: We conclude that ANA testing should preferably be requested in the presence of clinical findings associated with rheumatologic disorders.

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.