Multisystem Inflammatory Syndrome in Children in a 15-Year-Old Male with a Retropharyngeal Phlegmon.

This is a case of a 15-year-old male with an initial diagnosis of a retropharyngeal phlegmon who ultimately developed new symptoms and laboratory findings consistent with MIS-C. This case report demonstrates an atypical initial presentation for MIS-C that has not been reported in the literature.

Early identification of COVID-19 cytokine storm and treatment with anakinra or tocilizumab.

OBJECTIVE: To examine outcomes among patients who were treated with the targeted anti-cytokine agents, anakinra or tocilizumab, for COVID-19 -related cytokine storm (COVID19-CS). METHODS: We conducted a retrospective cohort study of all SARS-coV2-RNA-positive patients treated with tocilizumab or anakinra in Kaiser Permanente Southern California. Local experts developed and implemented criteria to define COVID19-CS. All variables were extracted from electronic health records. RESULTS: At tocilizumab initiation (n = 52), 50 (96.2%) were intubated, and only seven (13.5%) received concomitant corticosteroids. At anakinra initiation (n = 41), 23 (56.1%) were intubated, and all received concomitant corticosteroids. Fewer anakinra-treated patients died (n = 9, 22%) and more were extubated/never intubated (n = 26, 63.4%) compared to tocilizumab-treated patients (n = 24, 46.2% dead, n = 22, 42.3% extubated/never intubated). Patients who died had more severe sepsis and respiratory failure and met COVID-CS laboratory criteria longer (median = 3 days) compared to those extubated/never intubated (median = 1 day). After accounting for differences in disease severity at treatment initiation, this apparent superiority of anakinra over tocilizumab was no longer statistically significant (propensity score-adjusted hazards ratio 0.46, 95% confidence interval 0.18-1.20). CONCLUSIONS: Prompt identification and treatment of COVID19-CS before intubation may be more important than the specific type of anti-inflammatory treatment. Randomized controlled trials of targeted anti-cytokine treatments and corticosteroids should report the duration of cytokine storm in addition to clinical severity at randomization.

A protective Langerhans cell-keratinocyte axis that is dysfunctional in photosensitivity.

Photosensitivity, or skin sensitivity to ultraviolet radiation (UVR), is a feature of lupus erythematosus and other autoimmune and dermatologic conditions, but the mechanistic underpinnings are poorly understood. We identify a Langerhans cell (LC)-keratinocyte axis that limits UVR-induced keratinocyte apoptosis and skin injury via keratinocyte epidermal growth factor receptor (EGFR) stimulation. We show that the absence of LCs in Langerin-diphtheria toxin subunit A (DTA) mice leads to photosensitivity and that, in vitro, mouse and human LCs can directly protect keratinocytes from UVR-induced apoptosis. LCs express EGFR ligands and a disintegrin and metalloprotease 17 (ADAM17), the metalloprotease that activates EGFR ligands. Deletion of ADAM17 from LCs leads to photosensitivity, and UVR induces LC ADAM17 activation and generation of soluble active EGFR ligands, suggesting that LCs protect by providing activated EGFR ligands to keratinocytes. Photosensitive systemic lupus erythematosus (SLE) models and human SLE skin show reduced epidermal EGFR phosphorylation and LC defects, and a topical EGFR ligand reduces photosensitivity. Together, our data establish a direct tissue-protective function for LCs, reveal a mechanistic basis for photosensitivity, and suggest EGFR stimulation as a treatment for photosensitivity in lupus erythematosus and potentially other autoimmune and dermatologic conditions.

Transition of Care and Health-Related Outcomes in Pediatric-Onset Systemic Lupus Erythematosus.

OBJECTIVE: Transition from pediatric to adult care is a complex process and can negatively impact patients with chronic disease. We describe the transition experience of patients with pediatric-onset systemic lupus erythematosus (SLE) and its associated outcomes in adulthood. METHODS: A telephone survey of 41 pediatric-onset SLE patients was conducted following their transition to adult care. Data on medical and social outcomes during and after the transition were collected. Health status was compared to retrospectively collected baseline data at pediatric discharge. RESULTS: The mean ± SD followup interval was 5 ± 3.7 years; the mean ± SD age at followup was 24 ± 4.2 years. More than half of patients (22 of 41) experienced transition difficulties, primarily due to loss of insurance and emotional readjustment, which were associated with poor symptom control (P = 0.03) and multiple organ system involvement (P = 0.05) at followup. After the transition, most patients (35 of 41) were followed by an adult-care rheumatologist, and the majority (37 of 41) reported recent symptoms of active disease; 41% (13 of 29) had developed symptoms suggestive of new renal manifestations following transition. One-third (15 of 41) reported new or ongoing neuropsychiatric symptoms. Both renal and neuropsychiatric manifestations were associated with unemployment (P < 0.05). Direct referral by a pediatric rheumatologist was associated with fewer hospitalizations following transition (P = 0.04). CONCLUSION: The majority of patients transitioned successfully to adult rheumatologic care. Major challenges were loss of insurance and attachment to pediatric providers, highlighting the importance of a structured transition process that focuses on providing emotional and financial guidance. Disease activity in pediatric-onset SLE remains high throughout adulthood, with morbidity primarily related to renal and neuropsychiatric manifestations.

Pediatric systemic lupus erythematosus presenting with coronary arteritis: A case series and review of the literature.

OBJECTIVE: Pediatric-onset systemic lupus erythematosus (pSLE) is typically more aggressive in presentation than adult-onset lupus. Presenting manifestations of lupus in children and adults involve similar organ systems, with renal and neuropsychiatric involvement more common in pSLE. Cardiac manifestations are similar in the 2 groups, with pericarditis accounting for the majority of cardiac lupus at presentation. There are no reports to our knowledge of coronary arteritis as a presenting feature of pSLE. METHODS: This is a retrospective case series describing 4 pediatric lupus patients who presented with prominent coronary artery dilatation and a review of the literature regarding coronary artery involvement in lupus. RESULTS: Coronary arteritis appears to be a more common feature of pSLE than previously thought. Based on our experience, coronary artery changes tend to resolve once the SLE is treated. CONCLUSIONS: Early recognition of this disease manifestation may guide therapy and result in improved long-term cardiovascular outcomes.

Prolonged improvement of childhood onset systemic lupus erythematosus following systematic administration of rituximab and cyclophosphamide.

BACKGROUND: Although the combination of cyclophosphamide and rituximab has been utilized in case reports, there are no previous reports of the long term outcome of SLE treated systematically with this regimen. We report a pilot study to evaluate the efficacy of a systematically administered course of rituximab and cyclophosphamide over an eighteen month period to provide sustained improvement in childhood onset systemic lupus erythematosus (SLE). FINDINGS: Twelve patients with childhood onset lupus nephritis or corticosteroid resistant SLE received systematic treatment with a combination of rituximab (750 mg/M2 up to 1 gram) and cyclophosphamide (750 mg/M2: no patient exceeded 1.8 M2). Two administrations of rituximab and cyclophosphamide, two weeks apart, were administered at the start of study, six months later, and eighteen months later. Clinical data were collected and analyzed after sixty months of follow up. There was sustained improvement in all clinical parameters with a dramatic reduction in both mean SLEDAI score (10.1 to 1 at one year and 0 at five years p<0.005) and mean daily prednisone dosage (29.7 mg/day to 12.7 by one year and 7.0 mg/day at five years p<0.005), with sustained improvement in mean C3 (55.5 mg/ml to 113 at one year and 107.5 at five years p<0.001) which was maintained through sixty months of follow up. Serum immunoglobulin levels were transiently depressed but mean values were within the normal range for both IgG and IgM at one and five years. Few complications were observed (two episodes of febrile neutropenia during the first year of treatment were the only serious adverse events) and patients routinely reported sustained wellbeing. CONCLUSIONS: This pilot study demonstrates that a systematically administered course of rituximab and cyclophosphamide over an eighteen month period provided sustained relief for patients with childhood onset SLE which was maintained over a sixty month period, while minimizing the need for corticosteroids, without excessive toxicity.

Update on juvenile spondyloarthritis.

Spondyloarthritis (SpA) encompasses a group of disorders linked by overlapping clinical manifestations and genetic predisposition. Newer classification systems developed for adults with SpA focus on identifying individuals with axial or predominantly peripheral involvement. All forms of SpA can begin during childhood, and can be considered on a continuum with adult disease. Nevertheless, there are important differences in presentation and outcome that depend on age at onset. This article highlights these differences, what has been learned about genetics and pathogenesis of SpA, and important unmet needs for future studies.

Extreme and conventional cardiorespiratory events and epidemiologic risk factors for SIDS.

OBJECTIVE: To test the hypotheses that there is a lack of correlation between extreme events and epidemiologic risk factors for sudden infant death syndrome (SIDS), and if conventional events are normal, their numbers should increase once a circadian decrease in breathing rate is established. In addition, the number of events should decrease with maternal smoking. STUDY DESIGN: Three outcome variables were derived from the Collaborative Home Infant Monitoring Evaluation (CHIME) of 1082 infants: (1) at least 1 extreme event lasting > or = 30 seconds, (2) at least 1 conventional event lasting > or = 20 seconds, and (3) being part of the 50% of infants with the most events. RESULTS: Multivariate logistic regression analyses found that extreme events were not statistically associated with any known SIDS risk factors and occurred less often during the early morning. Healthy term infants had significantly fewer of these events compared with preterm infants, subsequent siblings of infants with SIDS, and infants with an apparent life-threatening event, a finding that was not evident after 43 weeks (3 weeks postterm). Conventional events increased during the night, whereas maternal smoking was associated with a decrease in conventional events. Apneic episodes persisting for > or = 40 seconds occurred in 1.8% of the infants. CONCLUSIONS: Extreme events are associated with immaturity and do not seem to be immediate precursors of or causally related to SIDS.