Evaluating the long-term effects of cognitive behavioural therapy as an early intervention for at-risk anxiety disorders among preschool children in Asia.

There are few evaluations of early intervention for the prevention of anxiety disorders in East Asia, and those that exist generally evaluate outcomes to a maximum of 6-12 months. The current study evaluated the long-term effect (5 years) of an anxiety prevention program presented to preschool children and their parents in Japan. Participants for the study were 10 inhibited children 5-6 years old and their parents. The parent's and children's program comprised group sessions of a cognitive-behavioural program. Parents and teachers completed the anxious/depressed, withdrawn and behavioural inhibition at pre-post-intervention and 3-month follow-up. Five years after starting the intervention, participants were invited to a diagnostic interview, Anxiety Disorders Interview Schedule (ADIS) to examine a long-term preventive effect of the intervention. The majority of children showed a reduction in anxious/depressed, behavioral inhibition, and approximately half showed reliable change according to parents' and teachers' reports. Moreover, the results indicated that 9 of the 10 children did not met the diagnostic criteria for anxiety disorders. These results suggested that the early intervention had preventive effects because the diagnostic criteria for anxiety disorders were not met in the follow-up assessment conducted five years later.

Randomised controlled trial of cultural-adapted and programme-adopted cognitive behavioural therapy for children and adolescents' anxiety in Japan: protocol for a Multi-, Inter-, and Cross-cultural Clinical Child Study (MIXCS).

INTRODUCTION: The primary objective of the Multi-, Inter-, and Cross-cultural Clinical Child Study (MIXCS) is to evaluate the hypothesis that the effects of cultural-adapted cognitive behavioural therapy (CA-CBT) and programme-adopted cognitive behavioural therapy (PA-CBT) for children and adolescents' anxiety are both superior to a psychological control (moral education control: MEC) for reducing child and adolescent anxiety disorders and symptoms as well as related constructs. The secondary objective is to explore commonalities and differences in therapy factors between CA-CBT and PA-CBT. METHOD AND ANALYSIS: The study has been designed as a randomised, controlled and assessor masked multicentre superiority trial with three groups: CA-CBT, PA-CBT and MEC. Primary outcome is remission of primary anxiety disorders evaluated by independent evaluators. Secondary outcomes are clinician's severity ratings, child self-reported anxiety symptoms, depressive symptoms, cognitive errors and family accommodation, as well as parent-reported anxiety symptoms, and family accommodation. Competence and adherence of treatment, therapy factors in treatment sessions are also measured based on behavioural observation. Finally, satisfaction and comprehension are collected. We aim to recruit at least 99 families for the analysis. Treatment will be delivered weekly for 10 sessions and assessment will be conducted 2 weeks before the treatment (pre), 3 months after the base date when the treatment starts (post), 6 months (six months follow-up) and 12 months (12 months follow-up) after the postassessment. ETHICS AND DISSEMINATION: The MIXCS study was approved by Doshisha University Research Ethics Review Committee, Kwansei Gakuin University Institutional Review Board for Medical and Biological Research Involving Human Subjects and Shinshu University Certified Review Board of Clinical Research. Regardless of the results, the primary outcome will be published in a journal, and if the efficacy and effectiveness of CA-CBT and/or PA-CBT are empirically supported, the authors will encourage dissemination of the programmes including the assessment system through key stakeholders in education, health, and welfare areas. TRIAL REGISTRATION NUMBER: UMIN000038128.

Cultural Adaptation and Implementation of Cognitive-Behavioral Psychosocial Interventions for Anxiety and Depression in Japanese Youth.

The present article reviews the current status of cognitive-behavioral therapy (CBT) interventions for anxiety and depression in Japanese youth. First, a literature review of youth CBT programs for anxiety and depression is provided. Through this process, we identify which program/protocol has been most researched within Japan. Second, through a systematic interview to the authors, the development process of four predominant programs is outlined. The programs included were a family CBT program for anxiety disorders (the Japanese Anxiety Children/Adolescents Cognitive Behavior Therapy program), two school-based prevention programs for anxiety and depression (Journey of the Brave and Phoenix Time), and a transdiagnostic protocol for anxiety and depression (Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Children and the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents). Third, cultural adaptation and modification of the programs are discussed from the scope of user-centered design principles as described by Lyon and Koerner (Sci Pract 23:180-200, 2016). As a result, changes in program content and material, as represented by the use of culture-friendly program names, acronyms, illustrations, and characters were endorsed in all of the programs. Structured but flexible session formats helped increase learnability and efficiency while keeping the cognitive load of providers and consumers low. A careful selection of providers, as well as quality training and consultation are important factors to maximize competency and ensure appropriate implementation. Application of existing time frames and staff who work in each setting were effective ways to increase scalability. Overall, it was shown that many of the modifications adopted overlap among successful programs; these represent the most basic and essential requirements for a program to be applicable to a wide range of contexts. Implications and further directions are explored.

Guided parent-delivered cognitive behavioural therapy for Japanese children and parents: a single-arm uncontrolled study.

BACKGROUND: Guided parent-delivered cognitive behavioural therapy (GPD-CBT) is an effective low-intensity treatment for childhood anxiety disorder in Western countries and can increase access to evidence-based psychological therapies. AIM: This study aimed to examine its feasibility in a Japanese sample. METHOD: Twelve children with anxiety disorders and their parents participated in the study, and ten children and parents completed the program. Participants were assessed at pre-, post- and one-month follow-up using a diagnostic interview for anxiety disorders, self- and parent-report measures for anxiety, depression, parental behaviour, and parental anxiety. RESULTS: Four children (40% of completers) were free from their primary diagnoses immediately following the brief treatment, and seven children (70%) at the one-month follow-up. Changes in disorder severity, child and parent reported anxiety symptoms, and child reported depression symptoms were consistent with those found in Western trials of GPD-CBT and of Japanese trials of more intensive CBT for child anxiety disorders that involves both the child and the parent. Moderate increases were also found in child reported parental autonomy behaviours; however, there were only small changes in parent self-reported anxiety. CONCLUSION: These results support the potential of GPD-CBT to increase access to evidence-based treatments for anxiety disorders in Japanese children.

Longitudinal Association between Maternal Autonomy Support and Controlling Parenting and Adolescents' Depressive Symptoms.

Most studies on autonomy support and controlling parenting rely on children's perceptions, despite the limitations of this approach. This study investigated congruency between autonomy support and controlling parenting reported by mothers and adolescents and their association with adolescents' depressive symptoms via basic psychological needs satisfaction. Participants included 408 Japanese mother-adolescent (Mage = 13.73, SD = 0.90, 52% female) pairs who completed a questionnaire at two time points four months apart. Results demonstrated low to moderate levels of mother-adolescent agreement. Cross-lagged regression models revealed that mothers' reported autonomy support positively predicted adolescents' basic psychological needs satisfactions, which was negatively associated with depressive symptoms. The independent roles of parenting reported by mothers and adolescents for adolescents' well-being were discussed.

Parental perception matters: Reciprocal relations between adolescents' depressive symptoms and parental perceptions.

A large body of research has shown that parents play a vital role in the development of adolescents' depression. However, previous research has overlooked the effects of a potentially critical factor, namely, parental perceptions, and beliefs about adolescents' depression. The present study examined whether parental perceptions of an adolescent's depressive symptoms predict longitudinal changes in adolescents' symptoms (i.e., the parental perception effect). The longitudinal relationship between adolescents' depressive symptoms and parental perceptions of the adolescents' symptoms was analyzed in three independent groups of parent-adolescent pairs (in total N = 1,228). Parental perception and monitoring effects were found in Studies 1B and 2 only in the depressive mood subscale. While a decreased enjoyment subscale showed a perception effect in Study 1A, we obtained null results from other studies. We synthesized the results by applying meta-analytic structural equation modeling to obtain a more robust estimate. The analysis qualified both perception and monitoring effects in both subscales. Our results suggest that when parents believe that their adolescent child is depressed, adolescents are cognitively biased by their parental perceptions over time, resulting in more severe depressive symptoms. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Implementation of a Transdiagnostic Universal Prevention Program on Anxiety in Junior High School Students After School Closure During the COVID-19 Pandemic.

School closures due to the coronavirus disease 2019 (COVID-19) pandemic have worsened mental health problems for children and adolescents worldwide. We aimed to examine the follow-up effectiveness of a transdiagnostic universal prevention program for anxiety of junior high school students after a nationwide school closure during the COVID-19 outbreak in Japan. A total of 117 junior high school students were included in the analysis. We used the Unified Universal Prevention Program for Diverse Disorders (Up2-D2) program; the Up2-D2 comprises cognitive-behavioral and positive psychological interventions provided over twelve 45-minute sessions. The program was originally implemented between June and July 2020, immediately after pandemic-related school closures had ended in Japan. The program assessments were based on students' responses to a questionnaire incorporating five scales to measure indicators such as internalizing and externalizing problems. Assessments were carried out before, immediately after, two-month, and six-month after implementing the program. Mixed models for the whole sample showed small anxiety improvement effects immediately post-intervention and two-month, and six-month assessments (g = -0.25, g = -0.44, and g = -0.30, respectively). The anxiety reducing effects were even greater for the higher-anxiety group at the post-, 2-month, and 6-month assessments (g = -1.48; g = -1.59; g = -1.06, respectively). Although there was no control group, these results indicate that the transdiagnostic universal prevention intervention reduce only anxiety, but not other outcomes (depression, anger, and self-efficacy) in junior high students returning to school following school closures related to the COVID-19 pandemic in Japan.

A One-Year-Old Girl With Human Parvovirus B19 Infection and Hypocomplementemia Mimicking Incomplete Kawasaki Disease.

Human parvovirus B19 (B19) is a single-stranded DNA virus that targets erythroid progenitor cells in the bone marrow. B19 causes erythema infectiosum in children, transient aplastic anemia, pure red cell aplasia, hydrops fetalis, and contributes to other illnesses. An association between B19 infection and hypocomplementemia and rheumatoid arthritis has been reported, but the underlying mechanisms remain unclear. We report the case of a 1-year-old Japanese girl with persistent fever, skin rash, transient edema of the extremities, hypoalbuminemia, and hypocomplementemia associated with B19 infection. We considered Kawasaki disease (KD) and collagen diseases, particularly systemic lupus erythematosus, in our differential diagnosis. B19 infection might be associated with serological features that suggest systemic lupus erythematosus and may present with clinical symptoms seen in KD. Especially during erythema infectiosum epidemics, we must consider B19 infection in the differential diagnosis of KD patients who demonstrate atypical clinical symptoms and unexplained laboratory findings.

Development of the Anger Children's Cognitive Error Scale and the Anger Children's Automatic Thought Scale.

BACKGROUND: Empirical studies between anger and anger-provoking cognitive variables in children and adolescents are lacking, despite numerous studies on internalising and externalising problems. AIM: The purpose of this study was to develop new questionnaires for anger-provoking cognitive errors and automatic thoughts, and examine relationships between anger, cognitive errors, and automatic thoughts in children and adolescents. METHOD: Participants were 485 Japanese children and adolescents aged 9-15 years old (254 females; average age 12.07; SD = 1.81). They completed the Anger Children's Cognitive Error Scale (A-CCES) and the Anger Children's Automatic Thought Scale (A-CATS), which were developed in this study, as well as the Anger Scale for Children and Adolescents and the Japanese version of Short Spence Children's Anxiety Scale. RESULTS: Both the A-CCES and the A-CATS had adequate reliability (internal consistency) and validity (face validity, structural validity and construct validity). A hierarchal regression analysis indicated that automatic thoughts were positively and moderately related to anger (ß = .37) after controlling for age, gender, anxiety symptoms, cognitive errors and interaction term. Moreover, a mediation analysis indicated that automatic thoughts significantly mediated the relationship between cognitive errors and anger (indirect effect, 0.24; 95% CI: .020 to .036). CONCLUSIONS: This study developed the new questionnaires to assess anger-provoking cognitive errors and automatic thoughts. In addition, this study revealed that automatic thoughts rather than cognitive errors are associated with anger in children and adolescents.

[Spinal Cerebrospinal Fluid Leak: Current Concepts and Management Policies].

In this article we provide an update on the recent developments in understanding the diagnosis and treatment of spinal cerebrospinal fluid(CSF)leaks. Patients with spinal CSF leak show an increasingly broad spectrum of clinical presentations including intractable whiplash-associated disorder(WAD)and orthostatic dysregulation in childhood, in addition to classical spontaneous intracranial hypotension(SIH). A simple understanding of the condition defined by the presence of low CSF pressure is no longer sufficient or accurate. Fat-suppressed T2-weighted magnetic resonance images and continuous epidural fluid infusion as a diagnostic therapy ensure accurate diagnosis. Accurate localization of the leak followed by targeted epidural blood patch(EBP)significantly improves the outcome of patients with spinal CSF leak. In addition to the known sites of CSF leakage, a newly identified CSF leak site, at the craniovertebral junction dural entry point of the vertebral artery(VA), is described.

Dural Entry Point of the Vertebral Artery: An Overlooked Route of Spinal CSF Leaks.

Spontaneous intracranial hypotension (SIH) is no longer considered rare. Its estimated annual incidence is 5 cases per 100,000 individuals, which is half the incidence of subarachnoid hemorrhage. Epidural blood patch (EBP) is indicated for SIH patients who do not improve with conservative treatment. Accurate determination of the cerebrospinal fluid (CSF) leak site is critical for a successfully targeted EBP. We report the case of a 43-year-old woman with SIH secondary to CSF leakage at the craniovertebral junction dural entry point of the vertebral artery (VA). We treated the patient 2 months after the onset of symptoms. Fat-suppressed T2-weighted spinal magnetic resonance (MR) images revealed a massive epidural fluid collection around the upper thoracic spine. Extravasation of contrast medium through the left VA-dural entry point was clearly visible on computed tomographic myelography. A cervical EBP was injected through the C1-2 interlaminar space. The patient had a smooth recovery and was asymptomatic, with normal spinal MR findings, 6 months after treatment. The possibility of CSF leakage from the dural entry point of the VA should be considered in SIH patients. EBP targeted at the VA entry point is proposed as a safe and effective treatment.

Evaluating the effectiveness of a transdiagnostic universal prevention program for both internalizing and externalizing problems in children: two feasibility studies.

BACKGROUND: The present study examined the effectiveness of the Universal Unified Prevention Program for Diverse Disorders (Up2-D2) for internalizing and externalizing problems for children aged 9-11 years. METHODS: We used two feasibility studies. The Up2-D2 entailed 12 sessions delivered by teachers; each session was developed based on cognitive-behavioral and positive psychological interventions. In Studies 1 and 2, 58 elementary school children aged 9-11 and 73 elementary school children aged 10-11 attended the Up2-D2. The teachers in Study 1 received 1.5 h of on-site teacher training for learning rationales for interventions, how to run the program, and received ongoing supervision by professionals with mental health expertise. In contrast, the teachers in Study 2 were given self-learning DVD materials in place of on-site training and ongoing supervision. RESULTS: Mixed models revealed that general difficulties, which is total score of both internalizing and externalizing problems, decreased in Study 1 but not in Study 2. Additional analyses for children with subclinical general difficulties revealed that general difficulties, internalizing problems, and externalizing problems decreased in Study 1, whereas in Study 2, general difficulties and internalizing problems decreased, except for externalizing problems. CONCLUSIONS: These results suggest that on-site teacher training and ongoing supervision are imperative for improving general difficulties in children at a universal level. In addition, universal preventive interventions by classroom teachers without on-site training and continuous supervision might be efficacious for reducing general difficulties and internalizing problems for children with subclinical difficulties.

A Comparison of Interactions Among Children, Parents, and Therapists in Cognitive Behavior Therapy for Anxiety Disorders in Australia and Japan.

Despite growing attention to the efficacy of culturally adapted cognitive-behavioral treatment (CBT) programs for children and adolescents, there is still little empirical and practical information available to therapists who adapt original treatment protocols to suit clients of a specific culture. The current study aimed to compare therapeutic interactions across CBT treatment delivered with two different cultural groups. We developed an observational coding system to examine behaviors exhibited by child, parent, and therapist during CBT sessions conducted in Australia and Japan for children with anxiety disorders. Our results demonstrated significant differences between the two countries with respect to the treatment readiness of children, the proportion of talking during the sessions by parents and children, therapists' laughter, length of silence during the first session, and parent indices of accommodation. In terms of transitions over time (i.e., first to last CBT session), parents in both countries tended to talk more during the last CBT session, whereas only Australian therapists talked less over time. The proportion of silence decreased over time during the Japanese sessions, and the amount of interruptions by parents increased over time for Australian sessions. Finally, our exploratory analyses demonstrated that a number of behavioral observations were correlated with anxiety treatment outcome at posttreatment. This study suggests that interactions between a child, parent, and therapist during CBT sessions may be affected by the culture in which the CBT session occurs, which could have implications for culturally adapted CBT programs.

The impact of the coronavirus disease 2019 pandemic on pediatric hospitalization in Kitami, Japan.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has drastically changed the recommended activities and environment for patients worldwide. Our aim was to assess the impact of COVID-19 on pediatric hospitalizations in Kitami, Japan. METHODS: A retrospective, single-center study was conducted on hospitalized patients aged 0-14 years at the Japanese Red Cross Kitami Hospital. We compared the incidence of pediatric patients hospitalized in 2020 with those in 2017-2019. RESULTS: The number of pediatric hospitalized patients dropped significantly in 2020 compared to that in 2017-2019 (median 43.0 vs 78.5 per month, P < 0.001). The patients were significantly older in 2020 (4.3 vs 3.4 years, P < 0.001). Hospitalization from respiratory (8.5 vs 30.5, P < 0.001) and gastrointestinal infections (3.0 vs 6.0, P = 0.004) significantly decreased. Admission due to respiratory syncytial virus (0.0 vs 4.0, P < 0.001), human metapneumovirus (0.0 vs 1.0, P = 0.005), influenza (0.0 vs 0.0, P = 0.009), adenovirus (0.0 vs 1.0, P = 0.003), and rotavirus infection (0.0 vs 0.0, P = 0.025) also decreased significantly. The <1-5 age groups significantly decreased (<1 year old, 6.5 vs 12.5, P < 0.001; 1-3 years old, 13.0 vs 29.5, P < 0.001; 4-5 years old, 5.5 vs 11.5, P < 0.001). Hospitalization due to foreign body ingestions increased significantly in 2020 (1.0 vs 0.0, P = 0.010). CONCLUSIONS: The COVID-19 control measures inadvertently reduced the number of hospitalized pediatric patients, especially younger children with respiratory and gastrointestinal infections.

Irritability and mental health profiles among children and adolescents: A result of latent profile analysis.

BACKGROUND: Irritability is a transdiagnostic symptom that accompanies both internalizing and externalizing problems. However, there has been a scarcity of research concerning the relationships between irritability and mental health profiles among children and adolescents. AIM: This study aimed to identify latent profiles in children and adolescents using anxiety, depression, oppositionality, and irritability. In addition, the profiles were further examined in their relationships with mental health symptoms. METHOD: The study analyzed data from 1867 children and adolescents aged 6-15 years from the COVID-19 Online-Survey for Children and Adolescents in Japan (J-COSCA). Parent-reported questionnaires were used in this study. RESULTS: A latent profile analysis detected five latent profiles. High oppositionality characterized the first profile ("oppositional": n = 405, 22%). High levels of depression and other less pronounced symptoms characterized the second profile ("depressed": n = 276, 15%). The third profile ("average": n = 602, 33%) presented average symptoms of anxiety, depression and oppositionality and low irritability. The fourth profile ("well-adjusted": n = 235, 13%) presented low values for all the applicable symptoms. The last profile ("comorbid": n = 308, 17%) exhibited high values for all the symptoms and the highest level of irritability of the five profiles. LIMITATION: We analyzed the data from a community sample alone after capturing it using parent-reported questionnaires. CONCLUSION: This study revealed that the five profiles (oppositional, depressed, average, well-adjusted, and comorbid) were identified, and children and adolescents in the comorbid profiles had high irritability as well as high anxiety, depression, and oppositionality.

Relationships between local school closures due to the COVID-19 and mental health problems of children, adolescents, and parents in Japan.

The widespread impacts of COVID-19 have affected both child and parent mental health worldwide. This study aimed to investigate the relationship between school closures due to COVID-19 and child and parent mental health in Japan. A sample of 1,984 Japanese parents with children and adolescents aged 6-15 years participated. The parents responded to online questionnaires about their own mental health and that of their children cross-sectionally. Participants were divided into three school situations based on the past week: full school closure, partial school closure, and full school open. Results indicated that 2.02% (n = 40) of the participants were in full school closure and 5.95% (n = 118) of the participants were in partial school closure. The results indicated that, after controlling for other variables regarding the pandemic, full school closure was associated with much higher scores in both child and parent mental health problems compared to full school open. Moderately higher scores were found only for anxiety symptoms in both children and parents under partial school closure compared to where schools were fully open. Consideration of the needs of families is necessary in the context of both full and partial school closures to prevent deteriorating mental health.

Changes in self-efficacy in Japanese school-age children with and without high autistic traits after the Universal Unified Prevention Program: a single-group pilot study.

BACKGROUND: Research has shown the efficacy of school-based programs for mental health problems in children. However, few studies have focused on the strengths of children, such as resilience, which is essential in preventing mental health problems. Moreover, no research has investigated the effect of a universal school-based program on children with increased autistic traits in mainstream classes. We examined the changes in children's self-efficacy, social skills, and general mental health after the implementation of a newly developed universal program, the Universal Unified Prevention Program for Diverse Disorders (Up2-D2), and whether similar changes occurred in children with and without higher autistic traits. METHODS: To assess possible changes associated with the program, questionnaires were collected from 396 children (207 boys and 189 girls) aged 9-12 years old before (T1), immediately after (T2), and three months after (T3) the implementation of the program. RESULTS: Results from a linear mixed-effects model showed a significant increase in children's self-efficacy at T2 (adjusted difference 0.49, 95% CI 0.03-0.94; p < 0.05) and T3 (0.78, 95% CI 0.32-1.23; p < 0.001). There were also significant positive changes in social skills and general mental health. Similar changes were observed in children with high autistic traits. Autistic traits at T1 did not contribute to the degree of change in self-efficacy. CONCLUSIONS: Our pilot study suggests that a universal program has the potential to promote positive attitudes and mental health in both at-risk and not-at-risk children.

Classroom-based cognitive behavioural therapy: a large-scale non-randomised controlled trial of the 'Journey of the Brave'.

BACKGROUND: In Japan, 'Journey of the Brave', a cognitive behavioural therapy (CBT)-based anxiety preventive education programme, was previously developed and its effectiveness examined in two small-scale controlled trials. These studies had some limitations, including a small number of participants and not having regular classroom teachers as programme facilitators. Therefore, we conducted a large-scale controlled trial, with teachers as programme implementers. METHODS: Twenty-seven elementary schools participated: 1622 and 1123 children were allocated to the intervention and control groups, respectively. The intervention group received a programme comprising ten 45-min sessions, while the control group underwent the regular school curriculum. Anxiety symptoms among participants were assessed using the Spence Children's Anxiety Scale (SCAS) at three stages (pre-intervention, post-intervention, and follow-up). RESULTS: Following primary analysis, estimated mean changes in SCAS from baseline to follow-up were - 4.91 (95% CI - 5.91, - 3.90) in the intervention group and - 2.53 (95% CI - 3.52, - 1.54) in the control group; the group difference was 2.37 (95% CI 1.42, 3.33, p < 0.0001). Children in the intervention group showed significant reduction in their anxiety score versus children in the control group. CONCLUSIONS: The results showed a statistically significant anxiety score reduction in the intervention group, thus verifying the programme's effectiveness. Trial registration The University Hospital Medical Information Network (UMIN): UMIN000032517. Registered 10 May 2018-Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037083.

Atypical Familial Mediterranean Fever in a Japanese Boy with Heterozygous MEFV p.Ser503Cys Exon 5 Variant.

Periodic fever syndromes are heterogeneous diseases. Familial Mediterranean fever (FMF) is one of the hereditary periodic fever diseases caused by a Mediterranean fever (MEFV) gene abnormality. FMF can be categorized as typical or atypical, based on clinical findings and genetic screening. Atypical FMF has a wide variation of clinical findings and disease-causing mutations of MEFV. Therefore, it is sometimes difficult to diagnose an unknown fever as FMF. To date, a large number of various typical and atypical FMF cases have been reported in Japan. Here, we describe a Japanese boy with heterozygous MEFV p.Ser503Cys exon 5 variant who developed periodic fever. He was treated with colchicine; a complete eradication of his fever and various accompanying symptoms have been subsequently achieved for more than a year. Given that there have been a few reports about patients with this variant, little is known about the genetic and phenotypic role of heterozygous MEFV p.Ser503Cys exon 5 variant. It is therefore imperative to consider atypical FMF as a differential diagnosis when a periodic fever is encountered. Furthermore, we suggest that it is worthwhile to integrate MEFV gene analysis with the potential effects of colchicine treatment in patients with periodic fever.