Consensus Middle East and North Africa Registry on Inborn Errors of Immunity

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. Methods: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. Results: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG). Conclusions: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

P043 Predictors of mortality in childhood-onset Systemic Lupus Erythematosus

Abstract Background Pediatric Systemic Lupus Erythematosus (pSLE) is a severe autoimmune disease due to its serious multi-visceral disorders, its morbidity causing deleterious and sometimes permanent effects. The objective is to determine the prognostic predictive factors of death in pSLE. Methods This was a prospective, descriptive, multicentre study, including patients less than16 years of age with SLE according to the criteria SLE of the American College of Rheumatology over a period of 36 months (2015–2018) carried out in the CHU Nefissa Hamoud in Algiers. The number of deaths during this follow-up period was determined and compared with surviving patients in several parameters (demographic, clinical, laboratory, therapeutic and disease activity). Disease activity was estimated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the use of which has been validated in children and damage and sequelae were appreciated by the Systemic Lupus International Collaborating Clinics (SLICC). Means, percentages and χ2 tests were specified. The multivariate analysis of logistic regression was used to determine prognostic factors associated with the outcome variable. P values &amp;lt;0.05 were considered statistically significant. Results 83 patients were collected and divided into two groups: deceased and survivors in which different parameters were compared and analyzed. Results: Female: male ratio 1: 4.9, mean age at diagnosis 11.3 ± 3.62. Clinical involvements at diagnosis were: cutaneous (100%), hematological (79.5%), articular (65, 1%), renal (44, 6%), neurological (41%), hepato-digestive (41%), cardiac (27, 7%), pleuropulmonary (19, 3%) and ocular involvement (7, 2%). The mean of SLEDAI was 22.11 ± 11.87 [interquartile range 2–53]. The prevalence of death was 11% of cases with an average age of death of 11 years [interquartile range 5–15 years]. The comparison of the two groups demonstrated a significant association between death and the following parameters: renal and neurological damage respectively: ((P = 0.03), (P = 0.02)), macrophage activation syndrome (MAS) (P = 0.0002), infections (P = 0.027), disease activity (P = 0.006) and damage score (P = 0.001). The mean SLEDAI activity in deceased patients was 32 ± 11.9 [interquartile range 17–53], compared with surviving patients which was 20.9 ± 11.4 [interquartile range 2–51]. Multivariate analysis with logistic regression revealed two major predictors of death, namely neurological involvement (odds ratio = 6,093 95% confidence interval ((1,1 8 0 ∼ 31 446)) and macrophage activation syndrome. Adherence to treatment was a protective factor: ([0.016 (0.001–0.353)]. Conclusion These results showed that pediatric systemic lupus erythematosus exhibits an aggressive and severe phenotype with an unpredictable course. Studies are needed in children in order to specify and develop prognostic predictive factors and to identify patients at high risk of early mortality in order to design early and effective care of this vulnerable entity of lupus disease. Keywords Child, Systemic Lupus Erythematosus, mortality </jats:sec

O004. Assessment of the impact of lupus nephritis on clinical, biological parameters, disease activity and mortality in pediatric Systemic Lupus Erythematosus

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple organ systems. Kidney involvement is one of the most frequent and severe manifestations of pediatric systemic lupus erythematosus (pSLE), seriously affecting the prognosis. It usually manifests as glomerulonephritis of varying severity. Objective: Knowledge of the correlation of lupus nephritis (LN) with clinical, biological, immunological parameters, disease activity and mortality in pediatric systemic lupus erythematosus is limited. This study aims to describe the impact of renal involvement with these different determinants. Methods This was a prospective, multicenter, descriptive 36-month study (January 2015 - December 2018) including patients less than 16 years of age with LN. The presence of LN was defined according to the American College of Rheumatology classification SLE criteria. The LN class was determined by renal biopsy and was classified according to the Morphology in Kidney International Society of Nephrology (ISN)/Renal Pathology Society (RPS) 2004 classification of lupus nephritis. The disease activity was estimated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the use of which has been validated in children. Means, percentages and Chi-square tests were specified. P values less than 0.05 were considered statistically significant. Results We included 83 patients in this study. 37/83 patients (44.6%) developed LN with the following urinary signs: 92% of proteinuria (mean 3366.147 mg ± 2785.93 / 24h) including 2/3 of cases of nephrotic syndrome, 81% of hematuria, 14% of acute renal failure with significant reduction in glomerular filtration rate (average creatinine clearance of 32.42 ml / min) and 12% high blood pressure. Out of a total of 30 renal biopsies interpreted at disease diagnosis, 73.4% diffuse proliferative glomerulonephritis forms were observed: (III (30%), IV (36.7%) and VI (6, 7%)). Lupus nephritis were significantly correlated with hypocomplementemia in its C3 (P = 0.00002) and C4 (P = 0.00005) fraction, lymphopenia (P = 0.02), anti-DNA antibodies (P = 0.026), SLEDAI (P = 0.00001) and mortality (P = 0.03). The most frequently used induction drugs for LN classes III, IV and VI were pulsed intravenous methylprednisolone (500 mg daily for 3 doses) in combination with low dose intravenous cyclophosphamide (23%) in the short term (500 mg/m2/15 days X 6) followed by mycophenolate mofetil (28%) (600mg/ m2 in two daily doses) as maintenance treatment associated with a daily dose of oral glucocorticoids with a gradual decrease until reaching the minimum amount necessary to control the disease. All of our SLE patients with nephritis were treated with HCQ with a significant correlation with the decrease in SLEDAI. During the first two years of disease progression, the frequency of LN increased to 43/83 (51.8%) mainly in these severe forms: (IV (41.7%), V (2.8 %). The progression to chronic renal failure had a prevalence of 6, 9% (3/43) of cases; these were mainly patients with severe lupus nephritis (III, and IV) Conclusion Nephritis is a major risk factor for morbidity and mortality in pSLE; LN in children is most often proliferating and more active. The early diagnosis and management of kidney damage are the only guarantee of a good course and prevention of the progression of chronic renal failure. Keywords lupus nephritis; child; systemic lupus erythematosus; disease activity, mortality. </jats:sec

P041 Systemic Lupus Erythematosus in Algerian Children: clinical, immunological profile and prognosis

Abstract Background Pediatric Systemic Lupus Erythematosus (pSLE) is a chronic mutisystemic autoimmune disease with complex clinical manifestations whose diagnosis is not always easy and the course is generally severe and the treatment is not very well codified and often extrapolated from that of adults. This study aims to describe the clinical, immunological, therapeutic characteristics and short outcome of systemic lupus erythematosus in Algerian children. Methods This was a prospective, multicentre and descriptive study 36 months (January 2015 - December 2018) at the department of Pediatrics of University Hospital Nefissa Hamoud ex Parnet Algiers. Children less than16 years of age fulfilling the American College of Rheumatology SLE criteria were included. Disease activity estimated by Systemic Lupus Erythematosus Disease Activity index (SLEDAI) whose use has been validated in children and damage index based on Systemic Lupus International Collaborating Clinics (SLICC) score were determined. Results Eighty-three (83) patients were studied. Female: male ratio was1:49. Mean ages at lupus onset and diagnosis were respectively: 10, 12 ± 3, 88 and 11, 3 ± 3, 62 years. All patients had skin involvement while constitutional signs including fever and asthenia were observed in (98.8%). Rheumatological, renal, neuropsychiatric, cardiac, hepato-digestive, pleuropulmonary and ocular disorders were observed respectively: 65, 1%, 44, 6%, 41%, 27, 7%, 41%, 19, 3% and 7, 2%. All patients were positive for antinuclear antibodies. Anti-double-stranded DNA (75%) was the most frequently observed autoantibody profile. Antiphospholipid antibody positivity was noted in 52% whereas hypocomplementemia in fractions C3, C4 was observed in 55% and 56% respectively. In our study, the severe forms were more frequent (83%) than the mild ones (17%) with a significant difference (P = &amp;lt; 10–6). Overall, the mean SLEDAI at disease onset was 22.11 ± 11.87 with high activity ≥ 20 in 59% of cases. The mean damage score was 1.8 ± 2.045 (interquartile range 0–8). Among induction drugs, oral corticosteroids were the most frequently used (92%), and in a third of cases intravenously at high doses in combination with immunosuppressive therapy. In induction therapy, cyclophosphamide (CYC) was the most used drug (23%) compared with mycophenolate mofetil (MMF) (14%). Unlike the maintenance phase where MMF observed an increase (28%) vs (8%) CYC. The use of MMF was correlated with severe lupus nephritis with a significantly effective difference in the decrease in SLEDAI (P = 0.0001). The use of hydroxychloroquine (HCQ) was observed in 81% in induction and 89% in maintenance treatment. The correlation of HCQ use with survival was significantly positive (P = 0.04). Indeed, adherence to treatments and essentially HCQ was a protective factor, its odds ratio is &amp;lt; 1 with a significant p-value, [OR 0.016 95% CI (0.001–0.353)]. Mortality was estimated at 11%. Multivariable regression analysis showed that the neurological involvement (odds ratio = 6,093 95% confidence interval ((1,1 8 0 ∼ 31 446)) and macrophage activation syndrome were associated with a high risk of mortality. Conclusion we report a series of pSLE characterized by great clinical and biological heterogeneity. It follows a severe course of the disease with high disease activity at the diagnosis and therefore leads to high morbidity and mortality. However, these results must be confirmed by other pediatric studies which could form the basis of a diagnostic and therapeutic approach more adapted for children. Keywords Algeria, Child, Clinical features, Disease activity, lupus </jats:sec

Production and Maintenance Scheduling Supported by Genetic Algorithms

Part 1: Design and Deployment of Assembly SystemsInternational audienceThe market demand has changed in recent years due to increased interest in more customized and diversified products by the consumers, leading to a change in production lines, which are becoming more flexible and dynamic. At the same time, the amount of data available in the factories is growing more and more, thereby the number of errors in the production schedule may occur often. Several approaches have been used over time to plan and schedule the shop-floor production. However, some only consider static environments, where the tasks are allocated to the machines, not considering that machines may not be available and sometimes maintenance interventions are needed. The introduction of maintenance increases the scheduling complexity and makes it harder to allocate the tasks efficiently. So, new solutions have been proposed, giving manufacturing systems the ability to quickly adapt to some disturbances that may occur. Thus, Artificial Intelligence approaches have been adopted to do the task allocation for the shop-floor. Those approaches can find suitable solutions faster than traditional approaches. This article proposes an architecture, based on Genetic Algorithm, capable of generating schedules including both production and maintenance tasks

P084 Recurrent fever in children: why not a mevalonate kinase deficiency?

Abstract Background Mevalonate kinase deficiency (MKD) is a rare autosomal recessive auto inflammatory disease. The clinical spectrum of this disease is a continuum ranging from the moderate form of Hyper-IgD syndrome (HIDS) to lethal forms of mevalonic aciduria (MA). An autoinflammatory disease should be considered in children with recurrent fever of unexplained origin. Case report M, 28 months old boy from a non-consanguineous marriage of Algerian parents, presented since the age of two months’ episodes of unexplained fever resistant to antibiotics and requiring several hospitalizations. Family history found that the mother and a maternal uncle experienced an unexplained recurrent fever. Personal history found episodes of fever lasting in average 6 days, with no obvious cause and recurring every 15–20 days; associated with bilateral cervical adenopathy, mouth ulcers, arthralgia, abdominal pain with vomiting and diarrhea. Clinical examination confirmed the fever with temperature of 38.7°, Chills and irritability, Multiple cervical adenopathy oral aphthae, tongue of geographical aspect, cervical pain and large joint arthralgia, tender abdomen with no organomegaly. Biologic workups found major inflammatory syndrome with hyper leucocytosis at 14X103/mm3 predominantly polynuclear, high CRP level, high ESR at 110 mm. Blood cultures and viral serologies were negative. Immunoelectrophoresis found elevated IgA, IgG and IgM with a normal IgD level. Chest X-ray and abdominal ultrasound were normal. The diagnosis of MKD in its moderate form was supported by elevated urinary mevalonic acid excretion to 5.1 mmol/mol during the febrile episode and subsequently confirmed by a 2nd contributory urine assay during another febrile episode. Conclusion MKD is a rare disease. The clinical spectrum of this condition is variable and could benefit of an effective treatment. Our patient developed a moderate form with a better long-term prognosis. </jats:sec