Assessment and comparison of probability scores to predict giant cell arteritis.

INTRODUCTION/OBJECTIVES: To assess and compare the performance of the giant cell arteritis probability score (GCAPS), Ing score, Bhavsar-Khalidi score (BK score), color Doppler ultrasound (CDUS) halo count, and halo score, to predict a final diagnosis of giant cell arteritis (GCA). METHOD: A prospective cohort study was conducted from April to December 2021. Patients with suspected new-onset GCA referred to our quaternary CDUS clinic were included. Data required to calculate each clinical and CDUS probability score was systematically collected at the initial visit. Final diagnosis of GCA was confirmed clinically 6 months after the initial visit, by two blinded vasculitis specialists. Diagnostic accuracy and receiver operator characteristic (ROC) curves for each clinical and CDUS prediction scores were assessed. RESULTS: Two hundred patients with suspected new-onset GCA were included: 58 with confirmed GCA and 142 without GCA. All patients with GCA satisfied the 2022 ACR/EULAR classification criteria. A total of 5/15 patients with GCA had a positive temporal artery biopsy. For clinical probability scores, the GCAPS showed the best sensitivity (Se, 0.983), whereas the BK score showed the best specificity (Sp, 0.711). As for CDUS, a halo count of 1 or more was found to have a Se of 0.966 and a Sp of 0.979. Combining concordant results of clinical and CDUS prediction scores showed excellent performance in predicting a final diagnosis of GCA. CONCLUSION: Using a combination of clinical score and CDUS halo count provided an accurate GCA prediction method which should be used in the setting of GCA Fast-Track clinics. Key Points • In this prospective cohort of participants with suspected GCA, 3 clinical prediction tools and 2 ultrasound scores were compared head-to-head to predict a final diagnosis of GCA. • For clinical prediction tools, the giant cell arteritis probability score (GCAPS) had the highest sensitivity, whereas the Bhavsar-Khalidi score (BK score) had the highest specificity. • Ultrasound halo count was both sensitive and specific in predicting GCA. • Combination of a clinical prediction tool such as the GCAPS, with ultrasound halo count, provides an accurate method to predict GCA.

A unique presentation of NLRP3-associated autoinflammatory disease: case report.

BACKGROUND: NLRP3-associated autoinflammatory diseases (NLRP3-AID) are rare genetic autoinflammatory diseases characterized by chronic inflammation and an urticaria-like rash. We report an unusual presentation of severe NLRP3-AID resulting in a significant diagnostic delay of more than three decades. CASE PRESENTATION: The patient presented with early-onset serositis as well as prominent peripheral eosinophilia with organ infiltration, in the absence of the classic urticaria-like rash. DNA analysis by next generation sequencing revealed a sporadic class 4 mutation c.1991T > C (p.Met662Thr) in the NLRP3 gene, confirming a diagnosis of NLRP3-AID at 36 years old. Although treatment with anti-interleukin 1 agent led to clinical remission, irreversible sequelae, namely intellectual disability and deafness, remained. CONCLUSION: This case highlights unique manifestations of NLRP3-AID, namely the absence of urticaria-like rash, eosinophilic organ infiltration, and pseudoseptic serositis. In order to avoid diagnostic delay and its dire consequences, NLRP3-AID should be suspected in patients displaying autoinflammatory features combined with serum and tissue eosinophilia and/or marked serositis, regardless of skin involvement.

Colour Doppler ultrasound and the giant cell arteritis probability score for the diagnosis of giant cell arteritis: a Canadian single-centre experience.

OBJECTIVES: The aim was to compare the accuracy of colour Doppler ultrasonography (CDUS) and temporal artery biopsy (TAB) to establish the final diagnosis of GCA and to determine how the GCA probability score (GCAPS) performs as a risk stratification tool. METHODS: Descriptive statistics were performed on a retrospective cohort of patients referred to our vasculitis referral centre between 1 July 2017 and 1 October 2020 for suspected GCA. CDUS, TAB, centre-specific TAB (vasculitis centre vs referring hospitals) and GCAPS were compared against the final diagnosis of GCA as determined by a GCA expert; CDUS was also compared with TAB results. RESULTS: Data from 198 patients were included: 60 patients with GCA and 138 patients without GCA. Sixty-two patients had a TAB. Using the final diagnosis by a GCA expert as a reference, the sensitivity, specificity, positive predictive value and negative predictive value were 93.3%, 98.5%, 96.6% and 97.1% for CDUS and 69.2%, 100%, 100% and 81.8% for TAB, respectively. The false-negative rate was 6.7% for CDUS and 30.8% for TAB. False-negative TAB mostly occurred when performed in referring hospitals (57.1%) as opposed to our vasculitis centre (21.1%). With a cut-off at 9.5 points, sensitivity for GCAPS was 98.3% and specificity 74.3%. CONCLUSION: CDUS of the temporal and axillary arteries showed a high sensitivity and specificity and helped to diagnose GCA in patients with negative TAB. We validated that GCAPS is a useful clinical tool, with a score of <9.5 making the diagnosis of GCA improbable.

DADA2 diagnosed in adulthood versus childhood: A comparative study on 306 patients including a systematic literature review and 12 French cases.

BACKGROUND: Deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease usually presenting before the age of 10 years. Non-specific clinical features or late-onset presentation may delay its diagnosis until adulthood. OBJECTIVE: To determine whether DADA2 diagnosed in adulthood is associated with specific characteristics compared to DADA2 diagnosed in childhood. METHODS: We pooled a cohort of 12 adult DADA2 patients followed in France with cases identified through a systematic literature review. For each patient, we determined the type of clinical presentation and assessed six key organ involvements. RESULTS: A total of 306 cases were included. Among the 283 patients with available data regarding age at diagnosis, 140 were diagnosed during adulthood and 143 during childhood. The vascular presentation of DADA2 was more frequent in the adult diagnosis group (77.9% vs. 62.9%, p < 0.01), whereas the hematological presentation (bone marrow failure) prevailed in the pediatric diagnosis group (10.0% vs. 20.3% p = 0.02). In patients with vasculopathy, severe skin manifestations developed in 35% and 10% of the adult and pediatric diagnosis groups, respectively. Conversely, fewer strokes occurred in the adult group presenting with systemic vasculopathy (54% vs. 81%). Symptomatic humoral immune deficiency (HID) was rarely a clinical presentation in itself (5% and 2.8%) but accompanied other phenotypes of DADA2, especially the hematological phenotype in the adult group (33% vs. 4%). CONCLUSION: DADA2 diagnosed in adulthood presents more often with a vascular phenotype and less often with bone marrow failure than DADA2 diagnosed in childhood. Adults diagnosed with DADA2 vasculopathy display more severe skin involvement but fewer strokes.

"Helicobacter pylori in familial mediterranean fever: A series of 120 patients from literature and from france".

INTRODUCTION: Familial Mediterranean Fever (FMF), the most common monogenic auto-inflammatory disease, is characterized by recurrent febrile abdominal pain. Helicobacter pylori infection (HPI), one of the most frequent infections worldwide, can mimic an FMF attack. OBJECTIVES: Identify FMF patients with HPI in a cohort of French FMF patients and the literature and identify features allowing to distinguish HPI from an FMF attack. METHODS: A retrospective study of all HPI cases was performed on the cohort of FMF patients fulfilling the Livneh criteria from the French Reference Center for rare Auto-Inflammatory Diseases and Amyloidosis (CEREMAIA). A systematic literature review of HPI in FMF patients was conducted according to the PRISMA guidelines. RESULTS: Eight French patients developed HPI, whose symptoms of epigastralgia, diarrhea, anorexia/weight loss, and nausea/vomiting differed from their typical abdominal FMF attacks. A total of 112 FMF patients with HPI have been described in the literature, including 61 adults. Diagnosis of HPI was made by gastroscopy (n = 43), labelled urea test (n = 55) or IgG serology by ELISA (n = 12). When performed, C-reactive protein was always elevated. Ten cases of interaction between colchicine and antibiotic therapy for HPI (clarithromycin (n = 9) and azithromycin (n = 1)) were reported. CONCLUSION: We described a total of 120 patients with typical FMF and HPI. When FMF patients develop atypical abdominal symptoms, upper gastrointestinal endoscopy with biopsies is essential to eliminate underlying HPI. Untreated HPI can lead to misdiagnosis of colchicine resistance with inappropriate prescription of an interleukin-1 inhibitor at a non-negligible cost.

AA Amyloidosis Secondary to Primary Immune Deficiency: About 40 Cases Including 2 New French Cases and a Systematic Literature Review.

BACKGROUND: Primary immune deficiencies (PIDs) are a heterogeneous group of disorders resulting from defects in immune system. They lead to increased susceptibility to infections and immune dysregulation. The resulting chronic inflammation can induce long-term complications, including AA amyloidosis (AAA). OBJECTIVES: To present the French cases of PID-related AAA and perform a systematic literature review to determine its main features and predisposing factors. METHODS: A systematic literature review was performed by searching MEDLINE up until 2019. New French cases were identified with the help of the Reference Center for Auto-Inflammatory Diseases and AA Amyloidosis and the Reference Center for Hereditary Immune Deficiencies. RESULTS: Forty patients were identified including 2 new French cases. PIDs were varied: immunoglobulin deficits (n = 30), chronic granulomatous disease (n = 3), hyper-IgM syndrome (n = 3), hereditary complete C4 deficiency (n = 1), leucocyte adhesion deficiency type 1 (n = 1), hyper-IgE syndrome (n = 1), and Chediak-Higashi syndrome (n = 1). The mean age at PID diagnosis was 22.2 ± 16.02 years. Renal involvement was the most common manifestation of AAA (80%). Infections were extremely heterogeneous; bacterial infection with pulmonary involvement was the most frequent. Bronchiectasis was particularly common (52.5%). The delay between the first symptoms of PID and AAA diagnosis was 16.18 ± 7 years. Thirteen concomitant diagnoses were made. Twenty patients died during follow-up. CONCLUSION: AAA is a rare life-threatening complication of PID, especially in cases of long diagnostic and therapeutic delays. Bronchiectasis should be considered as a warning sign of chronic inflammation and increased risk of AAA.

Systemic autoinflammatory diseases: Clinical state of the art.

Systemic autoinflammatory diseases (SAIDs) are defined as disorders of innate immunity. They were initially defined in opposition to autoimmune diseases due to the lack of involvement of the adaptive immune system and circulating autoantibodies. The four historical monogenic diseases are familial Mediterranean fever (associated with MEFV mutations), cryopyrinopathies (NLRP3 mutations), tumor necrosis factor receptor-associated periodic syndrome (TNFRSF1A mutations), and mevalonate kinase deficiency (MVK mutations). In the last 10 years, more than 50 new monogenic SAIDs have been discovered thanks to advances in genetics. Diagnosis is largely based on personal and family history and detailed analysis of signs and symptoms associated with febrile attacks, in the setting of elevated inflammatory markers. Increasingly efficient techniques of genetic analysis can contribute to refining the diagnosis. This review is a guide for the clinician in suspecting and establishing a diagnosis of SAID.

Non-amyloid liver involvement in familial Mediterranean fever: A systematic literature review.

INTRODUCTION: Familial Mediterranean fever (FMF), the most frequent autoinflammatory disease, is caused by mutations in the MEFV gene. It is characterized by recurrent febrile attacks of polyserositis. Liver abnormalities may develop during its course, but they remain poorly defined. OBJECTIVE: To describe liver involvement in FMF patients. METHODS: A systematic search was conducted through PubMed/Medline and Embase from 1946 to January 2020. All articles describing children and adults with FMF and liver involvement were included. Patients with amyloidosis were excluded. The selected full-text articles were independently reviewed by three investigators. RESULTS: Forty-three articles were identified, of which 20 articles with a total of 99 patients were included: 74 adults, 23 children and two patients of unknown age. Ten patients had cryptogenic cirrhosis, 48 had nonalcoholic fatty liver disease (NAFLD), four had Budd-Chiari syndrome (BCS), 12 had isolated hyperbilirubinaemia and 25 had elevated liver enzymes. CONCLUSION: Despite a low prevalence of metabolic risk factors, FMF may be associated with NAFLD and cryptogenic cirrhosis as a consequence of chronic or recurrent inflammation. FMF patients should be regularly screened for liver injury. The latter may be prevented and treated by daily colchicine intake. The evidence was insufficient to establish an association with BCS, hyperbilirubinaemia or autoimmune hepatitis.

Epidemiology of Castleman disease associated with AA amyloidosis: description of 2 new cases and literature review.

Introduction: HHV8-negative Castleman disease (CD) is classified as hyaline vascular (HV) type, or mixed or plasma cell (PC) types. It may present as multicentric CD (MCD) or unicentric CD (UCD). CD is a rare cause of AA amyloidosis (AAA). We aimed to report the main features of CD with secondary AAA through a description of new cases and a systematic literature review. Patients and methods: New cases were identified from the French National Reference Center for AAA. A systematic literature review was performed to identify HHV8-negative CD cases associated with AAA. Results: Thirty-seven patients were analysed, consisting of two new cases and 35 from literature. Twenty-three had UCD and 14 had MCD. PC was the main histologic subtype (n = 25; 68%) in both UCD and MCD patients. Surgical excision of UCD was performed in 21 patients (91%) with a favourable outcome, except for four patients (19%). Clinical and biologic remission was achieved in six patients with MCD (43%), all of whom were treated with anti-interleukin-6 (IL-6) therapy. Conclusions: AAA is a rare complication of CD, namely idiopathic MCD and UCD presenting with the PC histologic subtype. Surgical excision of UCD should be the first-line treatment whenever possible, while anti-IL-6 therapies seem effective for MCD.

Association of Vasculitis and Familial Mediterranean Fever.

Certain types of vasculitis occur more frequently and present differently in patients with familial Mediterranean fever (FMF). We assessed the characteristics of patients with FMF and systemic vasculitis through a systematic review of the literature. Medline was searched by two independent investigators until December 2017. We screened 310 articles and selected 58 of them (IgA vasculitis n = 12, polyarteritis nodosa (PAN) n = 25, Behçet's disease (BD) n = 7, other vasculitis n = 14). Clinical case reports were available for 167 patients (IgA vasculitis n = 46, PAN n = 61, BD n = 46, other vasculitis n = 14), and unavailable for 45 patients (IgA vasculitis n = 38, PAN n = 7). IgA vasculitis was the most common vasculitis in FMF patients with a prevalence of 2.7-7%, followed by PAN with a prevalence of 0.9-1.4%. Characteristics of FMF did not differ between patients with and without vasculitis. Patients with FMF and IgA vasculitis displayed more intussusception (8.7%) and possibly less IgA deposits on histological analysis than patients with IgA vasculitis alone. Patients with FMF and PAN had a younger age at vasculitis onset (mean age = 17.9 years), as well as more perirenal hematomas (49%) and CNS involvement (31%) than patients with PAN alone. Glomerular involvement was noted in 33% of patients diagnosed with PAN, suggesting an alternative diagnosis. Sequencing of the MEFV gene confirmed the presence of two pathogenic variants in 73% of FMF patients with IgA vasculitis or PAN. The majority of patients with BD were from one case series, and presented more skin, gastrointestinal, and CNS involvement than patients with isolated BD. In conclusion, FMF, particularly when supported by two pathogenic MEFV mutations, could predispose to IgA vasculitis, or a PAN-like vasculitis with more perirenal bleeding and CNS involvement.

Patients With Inflammatory Bowel Disease Are Unaware of the Impact of Smoking on Their Disease.

BACKGOUND: Tobacco is one of the most significant risk factors for inflammatory bowel disease (IBD). GOALS: The main objective was to assess the knowledge of patients with IBD regarding the effects of tobacco on their disease. Secondary objectives were to determine the source of their knowledge, the influence of their knowledge on their intent to quit smoking, and the association between patients' characteristics and their knowledge. STUDY: Patients with IBD completed a self-administered questionnaire on demographic data, severity of disease, and effects of tobacco on their disease. RESULTS: In total 259 patients [182 with Crohn's disease, 77 with ulcerative colitis (UC)] participated. The prevalence of current smokers, exsmokers, and nonsmokers was 19.6%, 40.2%, and 40.2%, respectively. Patients with Crohn's disease were more aware of the effects of tobacco on their disease compared with those with UC (57.7% vs. 13.0%, P<0.0001). In informed patients, the main source of information was the gastroenterologist (56.9%). The intent to quit smoking was superior in informed patients compared with those uninformed (78.6% vs. 47.8%, P=0.046). Older patients (odds ratio=0.97, P=0.01) and patients with UC (odds ratio=0.11, P<0.0001) were less likely to be informed. CONCLUSIONS: Only half of patients with IBD are aware of the risks of smoking associated with their disease, whereas their intent to quit smoking is directly related to their awareness. In the scope of IBD's treatment, management of smoking cessation should be undertaken in all smokers.

Two for one: a self-management plan coupled with a prescription sheet for children with asthma.

BACKGROUND: Despite strong recommendations in the asthma guidelines, the use of written self-management plans remains low among asthmatic patients. OBJECTIVES: To develop a written self-management plan, based on scientific evidence and expert opinions, in a format intended to facilitate its dispensing by health care professionals, and to test the perception of its relevance and clarity by asthmatic children, adolescents and adults. METHODS: Inspired by previously tested self-management plans, surveys of asthma educators, expert opinions and the 2004 Canadian Asthma Guidelines, the authors simultaneously developed French and English versions of a written self-management plan that coupled with a prescription. The self-management plan was tested in parents and their asthmatic children (aged one to 17 years), and it was revised until 85% clarity and perceived relevance was achieved. RESULTS: Ninety-seven children and their parents were interviewed. Twenty per cent had a self-management plan. On the final revision, nearly all items were clear and perceived relevant by 85% or more of the interviewees. Two self-management plans were designed for clinics and acute care settings, respectively. The plans are divided into three control zones identified by symptoms with optional peak flow values and symbolized by traffic light colours. They are designed in triplicate format with a prescription slip, a medical chart copy and a patient copy. CONCLUSION: The written self-management plans, based on available scientific evidence and expert opinions, are clear and perceived to be relevant by children, adolescents and their parents. By incorporating the prescription and chart copies, they were designed to facilitate dispensing by physicians in both clinics and acute care settings.