Utility of pan-immune-inflammation value as a predictor of the prognosis of childhood lupus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic inflammatory multisystemic disease. Monitoring disease activity thoughtout the disease course is important for effective management and assessment of disease outcome. OBJECTIVE: To assess whether the pan-immune inflammation value (PIIV) at diagnosis could predict organ involvement and disease activity in childhood SLE (cSLE) patients after 12 months of disease onst. METHODS: This is an observational retrospective multicenter study that comprised cSLE patients seen and followed at the participating centers between January 2010 and December 2022. All patients met the EULAR/ACR-19 criteria, were immunosuppressive drug-naïve at the time of SLE diagnosis and had a minimal follow-up period of 12 months. The data included clinical and laboratory findings and disease activity using the SLEDAI-2K. Receiver operating characteristic (ROC) curves were employed to determine the optimal cut-off value of PIIV and assess its predictive potential for disease activity, and organ involvement. RESULTS: A total of 125 patients (104 female) with a median age of 16.0 (IQR 5.6) years, a median age at disease onset of 10.9 (IQR 3.0) years, and a median disease duration of 4.8 (IQR 5.3) years were included. The most frequent involved organs at diagnosis were hematological (89.6%), musculoskeletal (68.8%), mucocutaneous (63.2%), and renal (58.4%). However, at a 12-month follow-up visit, the most frequent involved organs were renal (40.0%), hematological (39.2%), musculoskeletal (15.2%), and mucocutaneous (10.4%). The median PIIV at diagnosis was 139 (IQR 229.6), while the median SLEDAI was 12 (IQR 6.5) and 3.5 (IQR 7.0) at diagnosis and 12 months, respectively. An optimal PIIV cut-off of 250 was found to be a predicative for disease activity, with a sensitivity of 45% and a specificity of 86%. The study revealed that the PIIV successfully predicted four systems in our cohort of patients. CONCLUSION: Our work suggests the PIIV might be a reasonable predictor for organ involvement and disease activity in newly diagnosed cSLE, though further research, particularly larger studies, is required to validate these findings, especially regarding organ involvement.

Pattern and diagnostic evaluation of systemic autoinflammatory diseases other than familial Mediterranean fever among Arab children: a multicenter study from the Pediatric Rheumatology Arab Group (PRAG).

To define the spectrum and phenotypic characteristics of systemic autoinflammatory diseases (SAIDs) other than familial Mediterranean fever (FMF) in Arab children and to delineate diagnostic evaluation. Data retrospectively collected on patients with clinical and/or genetically proven SAIDs other than FMF at 10 tertiary Arab pediatric rheumatology clinics from 1990 to 2018. The collected data comprised the clinical findings and diagnostic evaluation including genetic testing, the provided treatment and the accrual damage related to SAIDs. A total of 144 patients (93 female) with a median age at onset of 2.5 (range 0.1-12) years were enrolled. The initial diagnosis was inaccurate in 49.3%. Consanguinity rate among parents was 74.6%. The median time-to-diagnosis for all SAIDs was 2.5 (range 0.1-10) years. There were 104 patients (72.2%) with a confirmed diagnosis and 40 patients with suspected SAIDs. Seventy-two had monogenic and 66 patients with multifactorial SAIDs while six patients had undifferentiated SAIDs. The most frequent monogenic SAIDs were LACC1 mediated monogenic disorders (n = 23) followed by CAPS (12), TRAPS (12), HIDS (12), and Majeed's syndrome (6). The most frequent multifactorial SAIDs was CRMO (34), followed by PFAPA (18), and early onset sarcoidosis (EOS) (14). Genetic analysis was performed in 69 patients; 50 patients had genetically confirmed disease. Corticosteroid used for 93 patients while biologic agents for 96 patients. Overall, growth failure was the most frequent accrual damage (36%), followed by cognitive impairment (13%). There were three deaths because of infection. This study shows a heterogenous spectrum of SAIDs with a high number of genetically confirmed monogenic diseases; notably, LACC1 associated diseases. Hopefully, this work will be the first step for a prospective registry for SAIDs in Arab countries.

Emergent high fatality lung disease in systemic juvenile arthritis.

OBJECTIVE: To investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA). METHODS: In a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data. RESULTS: LD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features. CONCLUSIONS: A rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.

Repeated attacks of hereditary angioedema in pediatric female.

A 16-year-old female presented to an outpatient clinic with a 13-year history of recurrent episodes of abdominal pain, vomiting and mild cutaneous swelling, either spontaneously or following minor trauma. The episodes occurred every 1-2 months. There was no family history of a similar complaint or hereditary angio-oedema (HAE). At the age of 16, evaluation confirmed the diagnosis of HAE type II, characterised by low C4 levels and reduced C1 esterase inhibitor function. The patient was prescribed tranexamic acid 1 g twice daily as well as C1 esterase inhibitor used as rescue medication during symptomatic episodes. This case report emphasises the importance of considering a diagnosis of HAE in patients with recurrent, unexplained abdominal pain, even in the absence of a positive family history of HAE.Abbreviations: ANA Antinuclear antibodies; C1-INH C1-inhibitor; CBC Complete blood count; FMF Familial Mediterranean fever; HAE Hereditary angioedema; IBD Inflammatory bowel diseases; SDP Solvent detergent-treated plasma; SLE Lupus erythematosus.

Quality indicators for care in juvenile idiopathic arthritis.

Objective: To develop a set of quality indicators (QIs) tailored to improve the care provided to children with juvenile idiopathic arthritis (JIA) in countries across the Asia-Pacific region. Methods: An adaptation of the Research and Development Corporation (RAND)/University of California, Los Angeles (UCLA) Appropriateness Method (RAM) was used. An initial set of 32 QIs was developed after a systematic search of the literature. These were presented to members of a Delphi panel composed of pediatric rheumatologists and other relevant stakeholders from the Asia Pacific League of Associations for Rheumatology Pediatric Special Interest Group (APLAR-Pediatric SIG). After each round, the mean scores for validity and reliability, level of disagreement, and median absolute deviation from the mean were calculated. Results: The panelists were presented with 32 QIs in two rounds of voting, resulting in the formulation of a final set of 22 QIs for JIA. These QIs are categorized within six domains of care, including access to care, clinical assessment, medications and medication monitoring, screening for comorbidities, counseling, and self-efficacy and satisfaction with care. Conclusion: These QIs have been developed to evaluate and improve the quality of care provided to children with JIA, aiming to enhance health outcomes and ensure that healthcare services are tailored to the unique needs of this patient population.

Anti-U1RNP-70kD-positive case of neonatal lupus presenting with seizure and incomplete heart block: a case report and literature review.

Neonatal lupus erythematosus (NLE) is an autoimmune disease caused by the transplacental passage of anti-Ro/SS-A and anti-La/SS-B. This can be less commonly seen with U1-ribonucleoprotein (U1RNP). Our patient is a 7-day-old male, who first presented with seizures. In addition, during an electroencephalogram, he was found to have an irregular heart rhythm. Looking further into the history, we found that the mother was aware that she had systemic lupus erythematosus (SLE). However, she had not been followed up with a rheumatologist. The workup for NLE found a negative anti-Ro/SS-A and anti-La/SS-B, with a positive U1RNP-70kD. U1RNP-70kD is a diagnostic test for mixed connective tissue disease in adults, but no research has been done on its significance in NLE. Despite having SLE, the infant's mother did not receive surveillance during her pregnancy, as the current guidelines are tailored for mothers with anti-Ro/SS-A and anti-La/SS-B. As a result, this calls for the extension of these guidelines to include the U1RNP-70kD antibody. In this case, the 70kD subtype of U1RNP was positive, which may have had a role to play in this unusual presentation. However, further research is needed to improve the care of mothers and babies with U1RNP-70kD.

Familial aggregation of juvenile idiopathic arthritis with other autoimmune diseases: Impact on clinical characteristics, disease activity status and disease damage.

OBJECTIVES: To evaluate the impact of family history of autoimmune diseases (FHADs) on the clinical characteristics and outcome of juvenile idiopathic arthritis (JIA). METHODS: We retrospectively reviewed children with JIA seen in 7 pediatric rheumatology clinics from 6 Arab countries. All included patients met the International League of Associations for Rheumatology classification criteria for JIA and had a disease duration greater than 1 year. Data were collected at the last follow-up visit and comprised clinical findings, including FHADs. Disease activity and disease damage were assessed by Juvenile Arthritis Multidimensional Assessment Report, and juvenile arthritis damage index (JADI) respectively. Disease activity was categorized as remission off treatment, remission on treatment, or active disease. RESULTS: A total of 349 (224 females) JIA patients with a disease duration of 5 (interquartile range 2.9-7.5) years were included. The most frequent JIA categories were polyarticular JIA and oligoarticular JIA, followed by systemic JIA. There were 189 patients with FHADs and 160 patients without FHADs. The most frequent FHADs were diabetes mellitus (21.2%), JIA (18.5%), rheumatoid arthritis (12.7%). Among patients with FHADs, 140/189 (74.1%) achieved clinical remission, while 131/160 (81.9%) patients without FHDs had clinical remission (odds ratio [OR] = 1.2, 95% CI 0.97-1.5). Rate of consanguinity, enthesitis-related arthritis (ERA) and psoriatic arthritis were higher in patients with FHADs (OR = 0.6, 95% CI 0.4-0.9 and OR = 1.2, 95% CI 1.1-1.4). Also, articular JADI correlated significantly with presence of FHADs (OR = 1.1, 95% CI 1.0-1.1). CONCLUSION: This study shows that autoimmune diseases cluster within families of patients with JIA with a high proportion of ERA and psoriatic arthritis. JIA patients with FHADs are likely to have more disease damage.

Impact of Ethnicity and Underlying Comorbidity on COVID-19 Inhospital Mortality: An Observational Study in Abu Dhabi, UAE.

BACKGROUND: The UAE reported its first cluster of COVID 2019 in a group of returned travellers from Wuhan in January 2020. Various comorbidities are associated with worse disease prognosis. Understanding the impact of ethnicity on the disease outcome is an important public health issue but data from our region is lacking. AIM: We aim to identify comorbidities among patients hospitalized for COVID-19 that are associated with inhospital death. Also, to assess if ethnicity is correlated with increased risk of death. Patients and Method. The study is a single-centre, observational study in Shaikh Shakhbout Medical City, Abu Dhabi. Patients admitted with COVID-19, between 1st of March and the end of May, were enrolled. Records were studied for demography, comorbidity, and ethnicity. Ethnicity was divided into Arabs (Gulf, North Africa, and the Levant), South Asia (India, Pakistan, Bangladesh, Nepal, and Afghanistan), Africans, the Philippines, and others. The study was approved by the Department of Health of Abu Dhabi. RESULTS: 1075 patients (972 males) were enrolled. There were 24 nationalities under 5 ethnicity groups. Mean (average) age was 51 years (20-81). 101 (9.4%) died with deceased patients being significantly older. Death risk was not significantly influenced by sex. Duration of hospitalization among survivors was 6.2 days (0.2-40.4) with older patients and men staying longer (P < 0.01). Comorbidities of diabetes, hypertension, cardiovascular disease, chronic renal disease, liver disease, and malignancy were associated with higher risk of mortality univariate, but only liver disease reached statistical significance after adjustment for age. The highest percentage of death was seen in Arab Levant (21.2) followed by the Asian Afghan (18.8); however, differences among ethnicities did not reach statistical significance (P = 0.086). CONCLUSION: COVID-19 outcome was worse in older people and those with comorbidities. Men and older patients required longer hospitalization. Ethnicity is not seen to impact the risk of mortality.

Consensus clinical approach for a newly diagnosed systemic juvenile idiopathic arthritis among members of the pediatric rheumatology Arab group.

BACKGROUND: Systemic juvenile idiopathic arthritis (sJIA) is a diagnosis of exclusion. The complex nature and clinical variety of the disease, as well as the vast clinical variation of disease presentation, may lead to difficulties in disease detection and subsequent delays in treatment. AIM: To provide a consensus guidance on the management of newly diagnosed sJIA patients among pediatric rheumatologists in Arab countries. METHODS: This work was conducted in two phases. The first phase utilized an electronic survey sent through an email invitation to all pediatric rheumatologists in Arab countries. In the second phase, a Task Force of ten expert pediatric rheumatologists from Arab countries met through a series of virtual meetings. Results obtained in phase one were prioritized using a nominal group and Delphi-like techniques in phase two. RESULTS: Seven overarching principles and a set of recommendations were approved by the Task Force to form the final consensus. CONCLUSION: This is the first consensus on a clinical approach for pediatric rheumatic diseases among Arab pediatric rheumatologists. It is presented as a guidance on the clinical approach to sJIA that requires further evidence, and future updates are anticipated.

Cumulative Damage in Juvenile Idiopathic Arthritis: A Multicenter Study From the Pediatric Rheumatology Arab Group.

OBJECTIVE: To report the cumulative articular and extraarticular damage in Arab children with juvenile idiopathic arthritis (JIA) and to identify variables that correlate with disease damage. METHODS: We conducted a multicenter, cross-sectional study among 14 pediatric rheumatology centers from 7 Arab countries. JIA patients who met the International League of Associations for Rheumatology classification criteria and had a disease duration of >1 year were enrolled. Disease activity status was assessed using the Juvenile Arthritis Multidimensional Assessment Report. Disease damage was assessed by the Juvenile Arthritis Damage Index, articular (JADI-A) and extraarticular (JADI-E). RESULTS: A total of 702 (471 female) JIA patients with a median age of 11.3 years (interquartile range [IQR] 8.0-14.0 years) were studied. Median age at disease onset was 5 years (IQR 2.0-9.0 years) and the median disease duration was 4 years (IQR 2.0-7.0 years). The most frequent JIA categories were oligoarticular JIA (34.9%), polyarticular JIA (29.5%), and systemic JIA (24.5%). Clinical remission was achieved in 73.9% of patients. At the last clinic visit, 193 patients experienced joint damage, with a mean ± SD JADI-A score of 1.7 ± 4.5, while 156 patients had extraarticular damage, with a mean ± SD JADI-E score of 0.5 ± 1.1. Patients with enthesitis-related arthritis had the highest JADI-A score. JADI-A correlated significantly with the presence of a family history of JIA. JADI-A and JADI-E had a significant correlation with long disease duration. CONCLUSION: Cumulative damage was common in this Arab JIA cohort, and consanguinity and JIA in a sibling were frequent findings and were associated with a greater cumulative damage.

Access to pediatric rheumatology care for Juvenile Idiopathic Arthritis in the United Arab Emirates.

BACKGROUND: This study looks at access to care for Juvenile Idiopathic Arthritis through pediatric rheumatology in the UAE, as an example of multi-ethnic society. METHODS: Patients with a diagnosis of Juvenile idiopathic arthritis were identified through the hospital electronic medical records system from January 1st 2011 to December 31st 2014. All residents of the United Arab Emirates hold an Emirates identity card. We divided our patients into two groups: Emirati-Emirates, who are native Emirati children and hold the Emirati nationality, as stated on their Emirates identity card, and who therefore have full, comprehensive access to free medical care; and non-Emirati-Emirates, who represent other nationalities, as stated on their Emirates identity card. The primary objective of this study is to look at access to care for Juvenile idiopathic arthritis through pediatric rheumatology in the two groups. The secondary objective is to look at the effect of having multiple types of healthcare insurance coverage on access to biologics. A retrospective review was carried out. RESULTS: Sixty-six patients with JIA identified: 33 Emirates and 33 non-Emirates. For Emirates, the mean time from onset to first appointment with pediatric rheumatologist and diagnosis is 9 months (range: 1-48), and for non-Emirates is 12.4 months (range: 1-96). Among the Emirates, 10 patients are currently on biologic with methotrexate. Among the non-Emirates, 15 are on biologic with methotrexate. Among the Emirates, 12 are currently in remission while on treatment, as are 10 non-Emirates. Regarding disability, one Emirati patient has blindness secondary to noncompliance while under previous treatment. One Non-Emirati developed joint deformities due to periods of noncompliance and no follow up. CONCLUSIONS: Delay in presentation to pediatric rheumatology has been identified as an important factor in our population, which is multi-cultural and multi-ethnic. Type of health care insurance cover did not affect number of patients getting biological therapy once patient seen in the pediatric rheumatology service.

Treatment of CD40 ligand deficiency by hematopoietic stem cell transplantation: a survey of the European experience, 1993-2002.

CD40 ligand (CD40L) deficiency causes recurrent sinopulmonary infection, Pneumocystis carinii pneumonia, and Cryptosporidium parvum infection. Approximately 40% to 50% of patients survive to the third decade: long-term survival is unclear. Hematopoietic stem cell transplantation (HSCT) is curative. We present a retrospective analysis of 38 European patients undergoing HSCT for CD40L deficiency in 8 European countries between 1993 and 2002. Donor stem cell source included 14 HLA-identical siblings, 22 unrelated donors, and 2 phenotypically matched parental stem cells (12 T-cell depleted). Of the patients, 34 engrafted and 26 (68%) survived; 3 had autologous reconstitution, 22 (58%) were cured, and 1 engrafted but has poor T-cell immune reconstitution. There were 18 evaluated patients who responded to vaccination. Of the patients, 12 (32%) died from infection-related complications, with severe cryptosporidiosis in 6. Grades 2 to 4 graft-versus-host disease (GvHD) associated with infection occurred in 6 of 12 fatal cases. HSCT cured 58% of patients, 72% of those without hepatic disease. Early T-cell function following whole marrow HSCT may limit cryptosporidial disease, but survival was similar after T-cell-depleted HSCT. Preexisting lung damage was the most important adverse risk factor. Further studies will determine optimal timing and type of HSCT.