Reliability and reproducibility of antinuclear antibody testing in pediatric rheumatology practice.

Antinuclear antibody (ANA) testing is common practice among health care practitioners when evaluating children and adolescents with non-specific symptoms including fatigue and aches and pains. When positive, ANA results often lead to referrals to pediatric rheumatologists as these antibodies may be key indicators for specific pediatric rheumatologic diagnoses. The reliability and reproducibility of ANA tests varies with assay techniques and validation and interpretation of results. In the following article, review of ANA testing in pediatrics is provided along with case examples that demonstrate the reliability and reproducibility of these results in specific scenarios common in the practice of pediatric rheumatology. Guidelines for more accurate utilization of ANA testing are presented with the aim to improve testing and interpretation by ordering clinicians.

Improving Hospital Infant Safe Sleep Compliance by Using Safety Prevention Bundle Methodology.

BACKGROUND AND OBJECTIVES: Sudden unexpected infant death often results from unsafe sleep environments and is the leading cause of postneonatal mortality in the United States. Standardization of infant sleep environment education has been revealed to impact such deaths. This standardized approach is similar to safety prevention bundles typically used to monitor and improve health outcomes, such as those related to hospital-acquired conditions (HACs). We sought to use the HAC model to measure and improve adherence to safe sleep guidelines in an entire children's hospital. METHODS: A hospital-wide safe sleep bundle was implemented on September 15, 2017. A safe sleep performance improvement team met monthly to review data and discuss ideas for improvement through the use of iterative plan-do-study-act cycles. Audits were performed monthly from March 2017 to October 2019 and monitored safe sleep parameters. Adherence was measured and reviewed through the use of statistical process control charts (p-charts). RESULTS: Overall compliance improved from 9% to 72%. Head of bed flat increased from 62% to 93%, sleep space free of extra items increased from 52% to 81%, and caregiver education completed increased from 10% to 84%. The centerline for infant in supine position remained stable at 81%. CONCLUSIONS: Using an HAC bundle safety prevention model to improve adherence to infant safe sleep guidelines is a feasible and effective method to improve the sleep environment for infants in all areas of a children's hospital.

Interplay of Anti-Viral Vaccines with Biologic Agents and Immunomodulators in Individuals with Autoimmune and Autoinflammatory Diseases.

Vaccines are an essential part of a preventative healthcare strategy. However, response to vaccines may be less predictable in immunocompromised people. While outcomes for individuals with autoimmune and autoinflammatory diseases have dramatically improved with treatment using immunomodulating and biologic agents, infections have caused significant morbidity in these people today often more than due to their underlying diseases. Immune-based biologic therapies contribute to these infectious complications. This review addresses anti-viral vaccines, their effectiveness and safety in patients treated with approved biologic agents and immune targeted therapy with a focus on vaccines against influenza, human papillomavirus, hepatitis B virus and varicella zoster virus. Preliminary information regarding SARS-CoV-2 anti-viral vaccines is addressed. Additionally, we present recommendations regarding the safe use of vaccines in immunocompromised individuals with the goal to enhance awareness of the safety and efficacy of these anti-viral vaccines in these high-risk populations.

Inflammatory Arthritis following Hepatitis B Vaccination in an Infant.

Inflammatory arthritis in children may be idiopathic in nature or may be due to or follow infections. Rare reports identify inflammatory arthritis temporally related to vaccination in children. Herein, we describe the first reported case of an infant who developed inflammatory arthritis following hepatitis B vaccination. A 10-day-old female presented for evaluation of decreased movement of the right lower extremity and right knee swelling. Of note, the patient received a hepatitis B vaccine in her right thigh at birth. A workup found the patient to have a negative ANA but the presence of HLA B27. Findings resolved using ibuprofen. A literature review identified reports of what has been termed "reactive arthritis" in adult patients following the hepatitis B vaccine, frequently in association with HLA B27. No prior pediatric cases have been published. Healthcare providers must be aware of the rare development of postvaccination inflammatory arthritis.

Comparison of Adults With Polyarticular Juvenile Idiopathic Arthritis to Adults With Rheumatoid Arthritis: A Cross-sectional Analysis of Clinical Features and Medication Use.

BACKGROUND/OBJECTIVE: Many individuals with juvenile idiopathic arthritis (JIA) have persistent disease into adulthood. Polyarticular JIA (pJIA) is often mislabeled as rheumatoid arthritis (RA) in adult rheumatology clinics, and treatment for adult pJIA patients is not well defined. We aimed to describe clinical features and medication use in the adult pJIA population in relation to an RA control cohort. METHODS: We performed a cross-sectional study of 45 adults with pJIA and 94 with RA seen from 2013 to 2017. Clinical characteristics including RA classification criteria were compared using χ and McNemar tests. Medication use was analyzed focusing on tumor necrosis factor inhibitor (TNFi) survival, and an accelerated failure-time model was developed for time to methotrexate initiation. RESULTS: Polyarticular JIA patients were less likely to be rheumatoid factor or cyclic citrullinated peptide antibody positive; fewer than half of pJIA subjects met the RA 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria. Time from diagnosis to methotrexate initiation was associated with longer disease duration in both groups (p < 0.01). Current TNFi use was more prevalent in pJIA patients (49% vs. 18%, p < 0.01), and TNFi use, particularly for etanercept, was sustained longer with a median drug survival of 4.41 years compared with 0.70 years in RA patients (p < 0.01). CONCLUSIONS: Although often considered together in adult rheumatology practice, adults with pJIA are distinct from patients with RA. Medication use markedly differed between the 2 populations with greater prevalence and duration of TNFi use in pJIA patients. Further study is needed to improve outcomes in this unique population.

The Impact of the Microbiome on Immunosenescence.

Human microbiome investigations now provide evidence that changes in the microbiome over time and their interaction with the immune, endocrine, and nervous systems are associated with a wide array of disorders. Human immunological studies typically absent a microbiome consideration in their investigations. An area of recent exploration is the role of the microbiome as a critical partner in the development and function of the human immune system in aging. It is well known that immunologic maturation is influenced by a lifetime of interactions of the host with its companion microbiome. It is generally not well recognized that intestinal microbes play an essential role in the development and expansion of gut mucosal and systemic immune function. Gut microbial communities of elderly people have different composition and behavior compared to healthy younger adults. Comorbidities associated with microbial pathogens and an aberrant immune system tend to increase with aging. This review underscores the impact of the human-microbiome interface on the development and function of the immune system and on immunosenescence. These changes have important implications regarding health and health system utilization in the elderly population.

Immunomodulatory interplay of the microbiome and therapy of rheumatic diseases.

Modulation of the immune system by microbes, especially from the gastrointestinal tract, is increasingly considered a key factor in the onset, course and outcome of rheumatic diseases. The interplay of the microbiome, along with genetic predisposition and environmental exposure, is thought to be an important trigger for rheumatic diseases. Improved identification of the relationship of disease-specific genetic alterations and rheumatic diseases has potential diagnostic and therapeutic applications. Treatment of rheumatic disorders is influenced by microbial actions but this interplay can be challenging due to variable and unpredictable responses to therapies. Expanded knowledge of the microbiome now allows clinicians to more precisely select ideal medication regimens and to predict response to and toxicity from drugs. Rheumatic diseases and associated therapies were among the earliest microbiome interactions investigated, yet it is notable that current research is focused on clinical and immunological associations but, in comparison, a limited number of studies regarding the microbiome's impact on treatment for rheumatic diseases have been published. In the coming years, further knowledge of immunomodulating interactions between the microbiome and the immune system will aid our understanding of autoimmunity and will be increasingly important in selection of therapeutic agents for patients with autoimmune and rheumatic diseases. In this review, recent literature regarding the bidirectional immunomodulatory effects of the microbiome with rheumatic diseases and current understanding and gaps regarding the drug-microbiome interface in the management of these disorders is presented.

Vaccine-Preventable Diseases Requiring Hospitalization.

BACKGROUND: Plain children often have lower immunization rates than non-Plain children. Penn State Health Children's Hospital is a tertiary medical center with large nearby Plain (Amish and Mennonite) communities. We sought to describe the characteristics of children hospitalized with vaccine-preventable diseases (VPDs). We hypothesized that Amish children would have a higher risk of VPDs than non-Amish children. METHODS: International Classification of Diseases, Ninth Revision codes were used to identify patients <18 years diagnosed with a VPD from January 1, 2005, to December 31, 2015, at Penn State Children's Hospital. Demographic information, immunization status, and outcomes were obtained from medical records. By using the number of children in our primary service area, we calculated the risk of VPD requiring hospitalization for Amish and non-Amish children. We assessed the relationship between Plain affiliation and vaccination status by using the Pearson correlation coefficient. RESULTS: There were 215 children with 221 VPDs. Most occurred in non-Plain children: 179 of 221 (81%). Except for pneumococcal infections, VPD occurred mostly in unvaccinated or immunocompromised children, regardless of Plain affiliation. There were 15 Haemophilus influenzae type b and 5 tetanus infections that occurred in children with an unvaccinated or unknown vaccination status. The risk of a VPD requiring hospitalization was greater for Amish than for non-Plain children (risk ratio: 2.67 [95% confidence interval: 1.87-3.82]). There was a strong correlation between Plain affiliation and lack of vaccination (r = -0.63, P < .01). CONCLUSIONS: Amish children had an increased risk of a VPD requiring hospitalization than non-Plain children. With the exception of those with pneumococcal disease, most vaccinated children hospitalized with a VPD were immunocompromised.

Immunotherapeutic Biologic Agents in Autoimmune and Autoinflammatory Diseases.

In recent decades, innovative strategies to treat patients with inflammatory, immunologically based diseases have advanced in concert with our increased understanding of molecular immunology. Recognition of the spectrum and pathophysiology of autoimmune and autoinflammatory disorders has allowed for the development of cutting-edge therapies for such patients. In this review, key immunotherapeutic approaches for treating inflammatory autoimmune disorders, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), as well as genetic autoinflammatory diseases, such as cryopyrin associated periodic syndromes, are addressed. Indications, risks and additional considerations in the use of these agents are reviewed.

Patient preferences and satisfaction in a multispecialty infusion center.

PURPOSE: Direct feedback from patients about their preferred modes of medication administration has been increasingly sought by providers to develop care programs that best match patient goals. Multispecialty infusion centers generally provide care to hematology-oncology (HO) and non-HO patients in one unit, with the same nursing staff. Our staff perceived that this was dissatisfying to our non-HO patients. We assessed patient satisfaction, as well as nursing and physician perceptions of patient preference/satisfaction with our infusion center, to determine whether a separate unit should be recommended when designing our new Cancer Institute Infusion Center. PATIENTS AND METHODS: A seven-question Likert scale satisfaction survey for patients, and a separate survey to assess nurses' and physicians' perception of patient satisfaction, were developed. The survey was administered to non-HO patients receiving infusions, doctors prescribing infusions, and nurses administering infusions. Results of the survey were compared between groups to assess differences in responses. RESULTS: Responses were received from 52 non-HO patients, 18 physicians, and 13 nurses. Patients had more satisfaction, on all survey items, with the multispecialty infusion center than had been realized by physicians and nurses. Analysis demonstrated that patients were satisfied with care in a multispecialty infusion unit and were in favor of continuing their care in this combined center. Total scores of patient surveys were significantly different (P<0.001) from those of physicians and nurses, who had assumed patients would prefer to have their care in a non-HO infusion setting. CONCLUSION: Understanding patient preferences is an important step in deciding the structure of infusion centers. Based on these survey conclusions, a combined multispecialty infusion center has been continued at our institution, thus improving quality by including patients in decision-making affecting their care.

The interference of monoclonal antibodies with laboratory diagnosis: clinical and diagnostic implications.

Diagnostic test interference is due to the presence of material that falsely changes an analytic test result. The development of monoclonal antibodies is discussed with focus on their extensive use as both therapeutic and diagnostic agents. In this review the interference of monoclonal antibodies with laboratory test methods and the potential impact on clinical care is addressed. Recognition of the types of interference, endogenous and exogenous, and the varied mechanisms by which monoclonal antibodies may cause interference are discussed in this report. Review of the literature identifies cases which exemplify the issues facing laboratorians and clinicians and describe the impact on patients. Approaches to reducing and eliminating sources of interference are also addressed. Education of ordering clinicians concerning the possibility of interference in at-risk patients is key in limiting the impact on care. Laboratorians and medical practitioners should be cognizant of the risk of interference to avoid incorrect management of patients.

Accelerated cutaneous nodulosis during infliximab therapy in a patient with rheumatoid arthritis.

Up to one fourth of patients with rheumatoid arthritis (RA) may have extraarticular findings such as subcutaneous nodules. These are discrete subcutaneous granulomatous nodules located on extensor surfaces, especially of the elbows. Over the past 10 to 15 years, there have been reports of accelerated cutaneous nodulosis in patients receiving methotrexate therapy. Recently, antitumor necrosis factor alpha (anti-TNFalpha) biologic therapy has become commonplace in the management of RA, especially in methotrexate-resistant or toxic patients. There have been recent reports of accelerated nodulosis in patients with RA on etanercept. We describe what we believe is the first case of accelerated cutaneous nodulosis resulting from infliximab anti-TNFalpha therapy in a patient with RA. One year after the initiation of infliximab, with RA in remission, our patient noted the rapid development of rheumatoid nodules of both hands. A biopsy was characteristic of a rheumatoid nodule, revealing palisading granulomas and fibrinoid necrosis.