UNASSIGNED: A major locus for spontaneous haploid genome doubling was detected by a case-control GWAS in an exotic maize germplasm. The combination of double haploid breeding method with this locus leads to segregation distortion on genomic regions of chromosome five. Temperate maize (Zea mays L.) breeding programs often rely on limited genetic diversity, which can be expanded by incorporating exotic germplasm. The aims of this study were to perform characterization of inbred lines derived from the tropical BS39 population using different breeding methods, to identify genomic regions showing segregation distortion in lines derived by the DH process using spontaneous haploid genome doubling (SHGD), and use case-control association mapping to identify loci controlling SHGD. Four different sets were used: BS39_DH and BS39_SSD were derived from the BS39 population by DH and single-seed descendent (SSD) methods, and BS39 × A427_DH and BS39 × A427_SSD from the cross between BS39 and A427. A total of 663 inbred lines were genotyped. The analyses of gene diversity and genetic differentiation for the DH sets provided evidence of the presence of a SHGD locus near the centromere of chromosome 5. The case-control GWAS for the DH set also pinpointed this locus. Haplotype sharing analysis showed almost 100% exclusive contribution of the A427 genome in the same region on chromosome 5 of BS39 × A427_DH, presumably due to an allele in this region affecting SHGD. This locus enables DH line production in exotic populations without colchicine or other artificial haploid genome doubling.

BACKGROUND: Behçet Disease (BD) is a chronic inflammatory vasculitis with thrombogenicity and multisystem involvement. Deep vein thrombosis (DVT) in the lower extremities is the most frequent manifestation of vascular involvement in BD. The causes of thrombosis vary widely and include congenital predisposition and acquired factors, but of all the thrombosis, the cause is rarely BD. Furthermore, there are few reports of treatment for thrombosis in BD.
METHODS: We herein describe the case of an Asian male patient aged 40 years, admitted to our hospital for left leg pain, edema, and swelling.
METHODS: We confirmed the DVT and pulmonary artery thrombosis (PAT) by contrast computed tomography angiogram. At the same time, the patient developed oral ulcerations and skin lesions consistent with BD.
METHODS: The patient was initially treated with anticoagulants. However, because the improvement of DVT was inadequate, we added colchicine in anticipation of anti-inflammatory effects. After that, anticoagulation was discontinued, and only colchicine was continuously prescribed.
RESULTS: We observed an almost complete resolution of DVT and PAT with no recurrence of thrombosis for 6 months after discharge.
CONCLUSIONS: This case shows us that we should consider BD as a differential diagnosis of DVT and that colchicine therapy is effective for inflammation-induced thrombosis in BD.

Familial Mediterranean fever is characterized by self-limited attacks of serositis and arthritis. However, substantial number of patients suffer from chronic complications of this disease, primarily involving musculoskeletal system. Treatment for these complications is challenging due to limited evidence. Interleukin-1 (IL-1) antagonists, tocilizumab and anti-tumor necrosis factor (anti-TNF) agents are off-label treatment options for the management of chronic manifestations of FMF, such as secondary (AA) amyloidosis, chronic arthritis and sacroiliitis. This paper presents a case series of four FMF patients who are refractory to IL-1 antagonists, anti-TNF agents and tocilizumab, who responded well to tofacitinib. The authors also conducted a comprehensive literature search for studies investigating tofacitinib use in FMF patients. Although still limited, current data suggest that tofacitinib could be a useful treatment option for FMF patients with associated inflammatory comorbid conditions and chronic manifestations of disease.

Behçet\'s disease is a rare chronic autoimmune disease affecting primarily Middle and East Asian populations between the ages of 20 and 40 years. Behçet\'s disease manifests with oral and genital mucocutaneous lesions, ocular disease, venous thrombosis, and central nervous system degradation. Treatment can be challenging and may require immunosuppressive agents and/or topical wound-care. While larger vascular involvement has been reported, digital ischemia due to small-vessel involvement has not been well described in the literature. Based on a systematic literature review, we were only able to find seven published cases of limb ischemia, none of which reported digital involvement. We present a unique case of Behçet\'s disease with severe digital ischemia and ulceration caused by small-vessel involvement. The patient was managed successfully with antiplatelet, immunosuppressants, and anti-inflammatories with complete resolution of the ischemic symptoms. By focusing on small-vessel involvement and digital ischemia, we provide insight into clinical presentation and treatment for this very rare vascular manifestation of Behçet\'s disease.

Familial Mediterranean fever (FMF) is the most common monogenic auto-inflammatory disease characterized by recurrent attacks of fever and serositis. Although colchicine is the first line treatment in FMF, 5-10% of patients do not respond to colchicine. Canakinumab, an anti-IL-1β monoclonal antibody, has been reported to be effective and safe in colchicine-resistant FMF patients, but the adequate duration and interval of treatment is still a matter of debate. Aim of this study was to evaluate the success of the standardized treatment protocol for canakinumab applied in our Pediatric Rheumatology Department in colchicine-resistant FMF cases with a review of the literature. Nine patients included in this study had indications for canakinumab use as colchicine resistance and recurrent corticosteroid need for pleural/pericardial effusions. Canakinumab was administered monthly for 6 months (initial treatment), bimonthly for 6 months (maintenance treatment), then treatment was discontinued. For the patients who developed a new attack after one-year treatment period, canakinumab was readministered with 3-month intervals (continuation treatment). The mean follow-up time beginning from the first canakinumab injection was 24.3 ± 10.2 (6-33) months. None of the patients had an attack during the first-year treatment. Four of the patients developed an attack 9.0 ± 2.9 (6-12) months after discontinuation of treatment and switched to the continuation treatment period, with no more attacks. We suggest that this standard protocol may be used successfully in colchicine-resistant FMF patients.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is a recurrent fever syndrome for which tonsillectomy is a therapeutic option curing the disease in most patients. Recurrence after remission with tonsillectomy is extremely rare. Increasing number of reports on diverse disease manifestations in PFAPA could give us clues about the disease etiopathogenesis. We aimed to describe a patient with recurrence of PFAPA syndrome after tonsillectomy and to review the previous studies including similar cases. We report a 17-year-old boy with PFAPA syndrome who experienced remission for 3 years after tonsillectomy and was later found to harbor an MEFV mutation when the disease relapsed. He responded well to colchicine treatment at relapse. The literature review revealed 14 articles describing 24 similar PFAPA patients. The therapeutic options include single-dose corticosteroids and nonsteroidal anti-inflammatory drugs during attacks, cimetidine, and resurgery. The presented case was the only one heterozygous for an MEFV mutation and treated with colchicine at disease relapse. Albeit rare, the reoccurrence of PFAPA after tonsillectomy could occur. The presence of such patients opposes with the hypothesis that the trigger or immune dysregulation in PFAPA pathogenesis resides in tonsils.

Behçet\'s disease (BD) is a systemic vasculitis affecting prominently the veins, which is usually diagnosed in adulthood, but can occur in children younger than 16 years in about 4-26% of cases. The therapy is based on several immune-suppressive drugs; in case of inadequate control and/or complications, the biologic therapy with anti-TNF drugs has been successfully used in adults. Here, we reported one pediatric case of BD with systemic (persistent/recurrent high fever), skin and mucosal manifestations (recurrent aphthous stomatitis, anal/penile ulcers, erythema nodosum and papulo-pustules), that were unresponsive to the conventional treatment with steroids and colchicine; however, he was successfully treated with adalimumab. Compared to adult patients, the experience with adalimumab in the treatment of pediatric BD is very limited. Indeed, through a systematic search in the medical literature, we retrieved 4 case reports and 2 case series, describing BD pediatric patients treated with adalimumab, in addition to three clinical studies including some BD children. The analysis and discussion of these available clinical experiences may indicate adalimumab as an effective and safe option to treat several forms of BD, in addition to BD-related chronic uveitis.

Gökçe İ, Altuntaş Ü, Filinte D, Alpay H. Polyarteritis nodosa in case of familial Mediterranean fever. Turk J Pediatr 2018; 60: 326-330. Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent self-limited attacks of fever accompanied by peritonitis, pleuritis, and arthritis. Protracted febrile myalgia syndrome (PFMS) is a rare form of vasculitic disease which is an uncommon dramatic manifestation of FMF, characterized by severe crippling myalgia and high fever. Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis affecting medium or small arteries. It is rarely observed in children, but its incidence increases in the presence of FMF. In this article we described a 14-year-old child diagnosed with FMF associated with PAN. Physicians should be aware of this possible association.

BACKGROUND: Because most patients with familial Mediterranean fever (FMF) have attacks without any prodromal symptoms, and since it is suggested that patients with FMF have subclinical inflammation even during remission, a daily continuous administration of colchicine is recommended for patients with FMF even during remission. However, it is possible that intermittent colchicine therapy only during FMF attacks prevents the attacks completely in patients with FMF with expectable attacks.
METHODS: A 31-year-old Japanese woman suffered high fever and arthralgia lasting for 2 to 3 days after each menstrual period\'s start. She was admitted to our hospital, and colchicine was administered immediately after her next period\'s start, and the febrile attack was completely prevented.
METHODS: We eventually diagnosed typical FMF.
METHODS: Her remission has been maintained by intermittent colchicine therapy.
RESULTS: The genetic analysis revealed the G304R heterozygous mutation in exon 2 of the MEFV gene. Cytokine analysis suggested subclinical inflammation during the remission period.
CONCLUSIONS: This case suggests that taking an extensive medical history (including the relationship between fever attack and menstruation) is important in the diagnosis of female patients with FMF. This case also suggests that a continuous administration of colchicine may have to be considered to regulate subclinical inflammation even in patients with FMF with completely expectable attacks.

BACKGROUND: Although 0.8 mg/kg is considered a lethal dose of colchicine, fatal cases of patients who followed a critical disease course after an intake below this lethal dose have been reported.
METHODS: An 18-year-old Japanese woman who had taken an overdose of prescription colchicine (15 mg; 0.2 mg/kg) was brought to our emergency out-patient department. Although her colchicine intake was below 0.8 mg/kg (considered the lethal dose), she reached a critical state and underwent three phases characterizing colchicine poisoning (gastrointestinal symptoms, multiple organ failure, and recovery). Her condition was critical, with a Sequential Organ Failure Assessment score of a maximum of 14.
CONCLUSIONS: Patients might reach a critical stage after colchicine ingestion at a non-lethal dose. Thus, it might be necessary to review which dose of colchicine should be considered lethal.