Why are you hitting yourself? Whole-exome sequencing diagnosis of monogenic autoimmunity.

Inborn errors of immunity may present with autoimmunity and autoinflammation as hallmark clinical manifestations. We aimed to identify the potential monogenic causes of autoimmune disorders in 26 patients from a pediatric reference hospital in Mexico through whole-exome sequencing. We specifically selected patients with a family history of autoimmune diseases, early-onset symptoms, and difficult-to-control autoimmune disorders or autoimmunity associated with infection predisposition. We identified the genetic variants that were compatible with the patients' phenotype in 54% of the patients. Autoimmune diseases are often caused by a combination of genetic factors, but cases that appear at a young age are resistant to treatment or occur in clusters, as well as the presence of autoimmune symptoms alongside infectious diseases should raise suspicion for an underlying inborn error of immunity.

Amaurosis as an initial presentation of Takayasu arteritis in children.

Visual disturbances in Takayasu arteritis (TA) are common but tend to be late manifestations of the disease. However, its presence at diagnosis must alert TA to avoid sight disabilities. Herein, we present two children with TA that debuted with vision loss, and the results of the literature review displayed 58 subjects with vision loss before the diagnosis of TA. The world English literature was reviewed by searching the PubMed database of the National Library of Medicine for the terms "Takayasu Arteritis" and "Blindness" or "Amaurosis fugax", from 190 to 2021. Cases eligible must present vision loss before or at TA diagnosis. Our two patients who presented with amaurosis fulfilled the criteria for TA diagnosis. The first patient had a bilateral and transient visual loss, whereas the second had monocular and permanent amaurosis. Both patients were cursed with hypertension and demonstrated large vessel compromise; their clinical picture improved with corticosteroids and immunosuppressant therapy. We identified in the literature review sixteen patients with TA in case reports and 42 in case series, plus our two cases presented herein with monocular or bilateral vision loss at the time of diagnosis. Previous literature indicated that amaurosis represents a severely advanced disease. Herein, we reported two children with amaurosis as their pivotal symptom; they had significant head and neck vascular alterations, so prompt and aggressive treatment is needed to prevent disease progression and disability. Transient or permanent vision loss must alert the physician to include Takayasu arteritis in the differential diagnosis.

Prognostic Factors at Diagnosis Associated With Damage Accrual in Childhood-Onset Systemic Lupus Erythematosus Patients.

Objectives: To associate prognostic factors present at diagnosis with damage accrual in childhood-onset systemic lupus erythematosus (cSLE) patients. Methods: We designed a cohort study of eligible children age 16 or younger who fulfilled the 1997 American College of Rheumatology (ACR) classification criteria for SLE. Excluded were those with previous treatment of steroids or immunosuppressants. The diagnosis date was cohort entry. We followed up on all subjects prospectively for at least 2 years. Two experts assessed the disease activity with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Mexican-SLEDAI (MEX-SLEDAI) every 3-6 months. Damage was measured annually, applying Pediatric Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) to their last visit. We analyzed prognostic factors by relative risks (RR) and used logistic regression to construct the clinimetric table. Results: Ninety patients with a median age of 11.8 years at diagnosis had a SLEDAI score of 15.5 (2-40) and a MEX-SLEDAI score of 12 (2-29); and of them, forty-eight children (53%) had SDI ≥ 2. The associated variables to damage (SDI ≥ 2) are as follows: neurologic disease RR 9.55 [95% CI 1.411-64.621]; vasculitis RR 2.81 [95% CI 0.991-7.973], and hemolytic anemia RR 2.09 [95% CI 1.280-3.415]. When these three features are present at diagnosis, the probability of damage ascends to 98.97%. Conclusion: At diagnosis, we identified neurologic disease, vasculitis, and hemolytic anemia as prognostic factors related to the development of damage in cSLE. Their presence should lead to a closer follow-up to reduce the likelihood of damage development.

IgA vasculitis (Henoch - Schönlein Purpura) as the first manifestation of juvenile Systemic Lupus Erythematosus: Case-control study and systematic review.

BACKGROUND: We have recognized 15 children with jSLE and the antecedent of IgA vasculitis (HSP). This association is not broadly present in the literature. AIM: To know the age and gender distribution of children with IgA vasculitis (HSP), compare it to our IgA vasculitis (HSP) + jSLE cases, and identify prognostic factors to develop jSLE within our case series, IgA vasculitis (HSP) vs. IgA vasculitis (HSP) + jSLE. METHODS: A systematic review was carried out to know the age and gender distribution of children with IgA vasculitis (HSP). The information obtained plus data from 110 children with IgA vasculitis (HSP) from the Instituto Nacional de Pediatría were used to compare groups and identify prognostic factors. We performed a case-control study in patients < 18 years, consisting of 15 cases retrospectively identified with IgA vasculitis (HSP) + jSLE, and 110 IgA vasculitis (HSP) control subjects. RESULTS: The information of 12,819 IgA vasculitis (HSP) subjects from the systematic review and 110 IgA vasculitis (HSP) controls was obtained and compared to our 15 IgA vasculitis (HSP) + jSLE cases. The mean age of IgA vasculitis (HSP) was 7.1-years vs. 10.4-years of IgA vasculitis (HSP) + jSLE at the HSP diagnosis. Female to male ratio of IgA vasculitis (HSP) was 1:1.33 vs. 1:0.25 of IgA vasculitis (HSP) + jSLE. Patients with IgA vasculitis (HSP) + jSLE had lower levels of Hemoglobin (Hb) compared to patients with IgA vasculitis (HSP) 109 g/L vs. 141 g/L. For the development of jSLE, we found older age and lower levels of Hb as prognostic factors with OR [95% CI]: 1.37 [1.06, 1.89] and 5.39 [2.69, 15.25], respectively. CONCLUSION: IgA vasculitis (HSP) + jSLE patients are older and have lower levels of Hb than patients with IgA vasculitis (HSP). It is necessary to confirm these findings through a prospective study.

Agreement among musculoskeletal pediatric specialists in the assessment of radiographic joint damage in juvenile idiopathic arthritis.

OBJECTIVE: To evaluate agreement among musculoskeletal pediatric specialists in assessing radiographic joint damage in juvenile idiopathic arthritis (JIA). METHODS: Two pediatric rheumatologists, 2 pediatric radiologists, and 2 pediatric orthopedic surgeons evaluated independently 60 radiographs of both wrists and hands of children with polyarticular-course JIA. Films were scored using an adapted and simplified version of the Larsen score, ranging from 0-5. Study radiographs were selected from 568 films used in a previous study aimed to validate an adapted pediatric version of the Sharp/van der Heijde (SHS) score. To enable comparison of specialists' scores with the adapted SHS score, the 60 radiographs were divided into 6 classes of severity of damage based on quintiles of the adapted SHS score. Agreement was evaluated in terms of absolute agreement and through weighted kappa statistics. RESULTS: The pediatric radiologists tended to assign lower scores and to provide more frequently scores of 0 than did the other specialists. Weighted kappa for the 3 pairs of specialists ranged from 0.67-0.69, indicating substantial agreement. Absolute agreement ranged from 51.3-55.7%, depending on the pair of specialists examined. Both absolute and weighted kappa concordance between specialists' scores and the adapted SHS score were poorer for the pediatric radiologist than for the other specialists. CONCLUSION: We observed fair agreement in the assessment of radiographic damage among pediatric specialists involved in the care of children with JIA. The radiologists tended to be more reserved than the rheumatologists and orthopedic surgeons in labeling radiographs as damaged or in considering changes as important.

[Brain hemorrhage in a patient with Kawasaki disease]. / Hemorragia cerebral en un paciente con enfermedad de Kawasaki.

Kawasaki disease is an acute, self-limiting vasculitis of unknown origin, characterized by fever, palms and soles edema, cervical lymphadenopathy, strawberry tongue, and non-exudative conjunctivitis. It is a multisystemic vasculitis that affects predominantly infants and young children. The most feared complication is the development of coronary aneurysms that occurs up to 25% of untreated patients; however there are reports of extra coronary involvement. Herein we present the case of a 2 year-old girl who had a severe symptomatology and persistent fever despite intravenous gammaglobulin. Two years later she presented right hemiparesia and headache, with data from CAT and MRI suggestive of brain mass and deviation of the midline, secondary to left frontoparietal haemorrhage that was treated with a craniotomy. She was discharged on prednisone, ASA and rehabilitation.

Intravenous immunoglobulin treatment for macrophage activation syndrome complicating chronic granulomatous disease.

OBJECTIVES: Chronic granulomatous disease is a rare phagocyte disorder characterized by an increased susceptibility to infections and inflammatory complications. We describe two patients with chronic granulomatous disease (CGD) complicated by macrophage activation syndrome (MAS) (secondary hemophagocytic lymphohistiocytosis) treated with intravenous immunoglobulin (IVIG). METHODS: A report of two cases of CGD complicated by MAS who were successfully treated with IVIG was made, and a comparison was made with ten other cases reported in the literature. RESULTS: MAS is a severe potentially fatal complication of CGD. Most cases are associated with Burkholderia cepacia and leishmaniasis infection. The treatment of these patients varies between centers, and one example is the use of the HLH-2004 protocol. IVIG could be an effective first line option for this complication in CGD patients. CONCLUSIONS: The exaggerated inflammatory response characteristic of CGD patients could play a role in the development of this complication. IVIG appears to be a safe and effective first line treatment in these patients.

Treatment of Kimura disease with intravenous immunoglobulin.

Kimura disease is an uncommon chronic inflammatory condition of unknown etiology and is characterized by painless subcutaneous nodules, usually affecting the head and neck, eosinophilia, and markedly elevated immunoglobulin E levels. Several reports have described the main modalities of treatment; both corticosteroids and surgery have provided good results, but occasionally corticosteroids cannot be tapered as the disease flares up. We report here the case of an 8-year-old boy diagnosed with Kimura disease who was successfully treated with 1 dose of intravenous immunoglobulin as a steroid-sparing agent.

Agreement between multi-dimensional and renal-specific response criteria in patients with juvenile systemic lupus erythematosus and renal disease.

OBJECTIVES: To evaluate change over time and level of agreement of renal-specific and multi-dimensional measures in juvenile systemic lupus erythematosus (SLE) with renal disease. METHODS: An analysis was made of 205/557 children with baseline 24-hour proteinuria >or=0.5 g. Data were collected at baseline, 6-, 12- and 24-month intervals. Using the Systemic Lupus International Collaborating Clinics (SLICC) renal index (change in proteinuria and urine sediment) as gold standard, responsiveness and discriminative ability analyses were used to identify key renal and multi-dimensional disease activity and damage measures for the evaluation of response to therapy. We also evaluated the kappa agreement between SLICC renal index and PRINTO/ACR juvenile SLE criteria (change in proteinuria, physician and parents evaluations, disease activity, health related quality of life [HRQOL]). RESULTS: Children with renal disease compared to children without renal disease, had a lower female rate and higher disease activity/response rate (p-values <0.01) but similar damage levels. Large responsiveness (standardised response mean >or=0.8) and statistical significant discriminative ability with the SLICC renal index 4 levels of response (improved, partially improved, stable and worsened) were observed for renal specific measures (proteinuria, urine sediment, renal sub-scores, p<0.0001) and for multi-dimensional variables (disease activity level and physician evaluation p<0.001). Agreement between the SLICC renal index and PRINTO/ACR criteria was moderate (0.57; 95% confidence intervals: 0.44-0.71). CONCLUSIONS: We propose to incorporate multi-dimensional measures (physician and parents' evaluations, disease activity and HRQOL), in addition to renal specific measures, in future clinical trials in juvenile SLE with renal involvement.