Systemic auto-inflammatory disorders (SAIDs) are a heterogeneous group of monogenic diseases sharing a primary dysfunction of the innate immune system. More than 50% of patients with SAID does not ...show any mutation at gene(s) tested because of lack of precise clinical classification criteria and/or incomplete gene screening. To improve the molecular diagnosis and genotype interpretation of SAIDs, we undertook the development of a next-generation sequencing (NGS)-based protocol designed to simultaneous screening of 10 genes.
Fifty patients with SAID, already genotyped for the respective causative gene(s), were massively sequenced for the coding portions of MEFV, MVK, TNFRSF1A, NLRP3, NLRP12, NOD2, PSTPIP1, IL1RN, LPIN2 and PSMB8. Three different bioinformatic pipelines (Ion Reporter, CLC Bio Genomics Workbench, GATK-based in-house workflow) were compared.
Once resulting variants were compared with the expected mutation list, no workflow turned out to be able to detect all the 79 variants known in the 50 DNAs. Additional variants were also detected, validated by Sanger sequencing and compared to assess true and false positive detection rates of the three workflows. Finally, the overall clinical picture of 34 patients was re-evaluated in the light of the new mutations found.
The present gene panel has resulted suitable for molecular diagnosis of SAIDs. Moreover, genotype-phenotype correlation has confirmed that the interpretation of NGS data in patients with an undefined inflammatory phenotype is remarkably difficult, thus supporting the need of evidence-based and validated clinical criteria to be used concurrently with the genetic analysis for the final diagnosis and classification of patients with SAIDs.
Abstract
Background
Type 1 diabetes mellitus could be associated with other autoimmune diseases, such as autoimmune thyroid disease, celiac disease, but the association with Familial Mediterranean ...Fever is rare, we describe a case of a boy with type 1 Diabetes Mellitus associated with Familial Mediterranean Fever (FMF).
Case presentation
A 13 year old boy already suffering from Diabetes Mellitus type 1 since the age of 4 years, came to our attention because of periodic fever associated with abdominal pain, chest pain and arthralgia. The fever appeared every 15–30 days with peaks that reached 40 °C and lasted 24–48 h. Laboratory investigation, were normal between febrile episodes, but during the attacks revealed an increase in inflammatory markers. Suspecting Familial Mediterranean Fever molecular analysis of MEFV gene, was performed. The genetic analysis showed homozygous E148Q mutation. So Familial Mediterranean Fever was diagnosed and colchicine treatment was started with good response.
Conclusion
Familial Mediterranean Fever could be associated with other autoimmune diseases such as Ankylosing Spondylitis, Rheumatoid Arthritis, Polyarteritis Nodosa, Behcet disease, Systemic Lupus, Henoch-Schönlein Purpura, and Hashimoto’s Thyroiditis. Association of type 1 Diabetes Mellitus and Familial Mediterranean Fever has been newly reported in the medical literature, this is the third association of these two diseases described in the medical literature so far.
Behçet's disease is a rare multi-systemic inflammatory disease with unknown etiology which involves principally oral and genital mucosa, skin and eyes. Average age at onset of the disease is about ...25-30 years, but it may be diagnosed before the age of 16. It is not very rare in Italy, even though there are limited data concerning epidemiology. Aim of this study is to describe the baseline data of an Italian cohort of patients with as having BD or probable BD.
We described the baseline data of the first national epidemiological study on children coming from 16 Italian Pediatric Rheumatologic Centers diagnosed by the treating physicians as having Behçet's Disease. Data on demographic characteristics, clinical features and therapy were collected. We then compared our findings to those of international pediatric cohort studies and also retrospectively evaluated the ability to diagnose BD using ISG, ICBD and, for the first time, the new PEDBD criteria.
The study included 110 patients (62 M, 48F). Average age at onset was 8.34±4.11 years. The frequencies of signs/symptoms were: recurrent oral aphtosis 94.5%, genital ulcers 33.6%, ocular 43.6%, gastrointestinal 42.7%, musculoskeletal 42.7%, neurological 30.9% and vascular involvement 10%. Thirty-two patients (29.1%) fulfilled ISG, 78 (70.9%) ICBD, 50 (45.5%) PEDBD criteria and 31 (28%) didn't fulfill any of them. The most frequently used treatments were colchicine and corticosteroids followed by immunosuppressants. Four patients received biologic therapy (anti TNF-α and anti-IL-1) to treat severe organ involvement.
Recurrent oral aphtosis was the most frequent clinical manifestation, followed by ocular involvement. Gastrointestinal lesions were more frequent in Italy than in non-European countries as opposed to genital ulcers. Skin, ocular and vascular manifestations had a higher frequency in males and genital ulcers in females. Constitutional symptoms were present in 44.5% and recurrent fever in one third of our population.
Only a few studies have reported long-term efficacy of interleukin (IL)-1 inhibition in systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still disease (AOSD). Herein we report on the ...effectiveness of anakinra (ANA), expressed in terms of drug retention rate (DRR), and evaluate the predictive factors of drug survival in a cohort of patients with sJIA and AOSD.
This is a multicenter study reviewing retrospectively the medical records from 61 patients with sJIA and 76 with AOSD, all treated with ANA in 25 Italian tertiary referral centers.
The cumulative retention rate of ANA at 12-, 24-, 48-, and 60-month of follow-up was 74.3%, 62.9%, 49.4%, and 49.4%, respectively, without any significant differences between sJIA and AOSD patients (
= 0.164), and between patients treated in monotherapy compared with the subgroup coadministered with conventional disease-modifying antirheumatic drugs (cDMARDs) (
= 0.473). On the other hand, a significant difference in DRR was found between biologic-naïve patients and those previously treated with biotechnologic drugs (
= 0.009), which persisted even after adjustment for pathology (
= 0.013). In the regression analysis, patients experiencing adverse events (AEs) {hazards ratio (HR) = 3.029 confidence interval (CI) 1.750-5.242,
< 0.0001} and those previously treated with other biologic agents HR = 1.818 (CI 1.007-3.282),
= 0.047 were associated with a higher HR of ANA discontinuation. The median treatment delay was significantly higher among patients discontinuing ANA (
< 0.0001). Significant corticosteroid-sparing (
= 0.033) and cDMARD-sparing effects (
< 0.0001) were also recorded. Less than one-third of our cohort developed AEs, and 85% were deemed mild in nature, with 70% of them involving the skin.
Our findings display an overall excellent DRR of ANA on the long run for both sJIA and AOSD, that may be further optimized by closely monitoring patient's safety issues and employing this IL-1 inhibitor as a first-line biologic as early as possible. Moreover, ANA allowed a significant drug-sparing effect and showed an overall good safety profile.
Scurvy is generated by lack of vitamin C; although it is considered a rare and past disease, scurvy continues to be detected in children with neurodevelopmental disorders and with selective diet ...habits. Identifying scurvy can be demanding due to the perceived rarity of the condition, and it can become a tricky diagnostic question given to the variety of nonspecific symptoms, including gingival manifestations. This study aims to identify most common clinical features in order to provide a complete picture of the signs and symptoms, and to offer clinicians the diagnostic tools for identifying patients suffering from scurvy. We present a case report of a child affected by scurvy; it has also been performed as a systematic review about scurvy in pediatric population. A search yielded 107 relevant studies since 1990. Most of the identified cases have shown oral, musculoskeletal and cutaneous manifestation that improved within a few days of starting vitamin C therapy. Identifying scurvy’s characteristic clinical features allows a timely diagnosis, thus avoiding invasive investigations. Pediatric dentists should possess adequate knowledge and experience to identify the main characteristics of scurvy. This can help facilitate a prompt diagnosis in order to provide timely intervention to the patient that is relatively ease and safe.
Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic nonbacterial osteomyelitis, is a rare, noninfectious inflammatory disorder that causes multifocal bone lesions with swelling ...and pain. Lytic and sclerotic bone lesions could be found on X-ray. Short tau inversion recovery magnetic resonance imaging (STIR MRI) shows bone marrow oedema, bone expansion, lytic areas and periosteal reaction. CRMO is characterized by periodic exacerbations and remissions of unclear/unknown pathogenesis.
A 10 years old girl, suffering from pain in her right shoulder since the age of 9 years presented to our Department. Thanks to clinical data, laboratoristic and radiological findings and bone biopsy CRMO was diagnosed. So patient started anti-inflammatory treatment and her conditions improved.
In a child with bone pain should be considered also rare condition as CRMO to perform a correct diagnosis and start an adequate treatment avoiding complications such as bone damage. This condition should be suspected in a child with recurrent bone pain, modest increase of inflammatory indices, lytic or sclerotic bone lesion on X Ray. Typical CRMO localizations are metaphyses of long bones, pelvis, clavicle, vertebral column, sternum, ribs, jaw, but any bone can be involved. The most common CRMO differential diagnosis is represented by infections, malignant bone tumors, Langerhans Cells Histiocytosis (LCH).
Few studies have reported the drug retention rate (DRR) of biologic drugs in juvenile idiopathic arthritis (JIA), and none of them has specifically investigated the DRR of interleukin (IL)-1 ...inhibitors on systemic JIA (sJIA). This study aims to describe IL-1 inhibitors DRR and evaluate predictive factors of drug survival based on data from a real-world setting concerning sJIA.
Medical records from sJIA patients treated with anakinra (ANA) and canakinumab (CAN) were retrospectively analyzed from 15 Italian tertiary referral centers.
Seventy seven patients were enrolled for a total of 86 treatment courses. The cumulative retention rate of the IL-1 inhibitors at 12-, 24-, 48-, and 60-months of follow-up was 79.9, 59.5, 53.5, and 53.5%, respectively, without any statistically significant differences between ANA and CAN (
= 0.056), and between patients treated in monotherapy compared to the subgroup co-administered with conventional immunosuppressors (
= 0.058). On the contrary, significant differences were found between biologic-naive patients and those previously treated with biologic drugs (
= 0.038) and when distinguishing according to adverse events (AEs) occurrence (
= 0.04). In regression analysis, patients pre-treated with other biologics (HR = 3.357 CI: 1.341-8.406,
= 0.01) and those experiencing AEs (HR = 2.970 CI: 1.186-7.435,
= 0.020) were associated with a higher hazard ratio of IL-1 inhibitors withdrawal. The mean treatment delay was significantly higher among patients discontinuing IL-1 inhibitors (
= 0.0002).
Our findings suggest an excellent overall DRR for both ANA and CAN that might be further augmented by paying attention to AEs and employing these agents as first-line biologics in an early disease phase.
A 9‐year‐old child with painful nodules on the leg Olivieri, Alma Nunzia; Gicchino, Maria Francesca; Piccolo, Vincenzo
Pediatric dermatology,
July/August 2023, 2023 Jul-Aug, 2023-07-00, 20230701, Volume:
40, Issue:
4
Journal Article
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