Autoinflammatory Diseases/Periodic Fevers.

Children with intermittent fevers present to pediatricians and other primary care child health providers for evaluation. Most patients will have self-limited, benign infectious illnesses. However, the possibility of a periodic fever syndrome should be considered if febrile episodes become recurrent over an extended period and are associated with particular signs and symptoms during each attack. This review discusses the current conceptualization of autoinflammatory diseases with specific focus and detail on familial Mediterranean fever; tumor necrosis factor receptor-associated periodic syndrome; mevalonate kinase deficiency; NLRP3-associated autoinflammatory disease; and periodic fever, aphthous stomatitis, pharyngitis, and adenitis. The genetic mutations associated with these clinical entities are identified, along with the historical nomenclature that predates the current pathogenetic understanding of these diseases. The episodic signs and symptoms seen across these periodic fever syndromes can be overlapping, but there are some distinguishing features that can be useful, and these are described. The disease course and potential complications, particularly amyloidosis, which is a variable risk in these conditions and a potential source of significant morbidity and mortality, are addressed. Treatment strategies are outlined, highlighting the advances in therapy that have resulted from the advent of proinflammatory cytokine-targeting biological agents.

Off-on-off-on use of imatinib in three children with fibrodysplasia ossificans progressiva.

The compassionate use of available medications with unproven efficacy is often in conflict with their clinical evaluation in placebo-controlled clinical trials. For ultra-rare diseases where no approved treatments exist, such as fibrodysplasia ossificans progressiva (FOP), routine clinical trial enrollment for available medications may be difficult to achieve. Therefore adaptive methods of evaluation are often desirable. Off-on-off-on (O4) approaches offer an opportunity to rapidly assess the potential symptomatic efficacy and tolerability of a medication with a limited number of patients and may aid in the design of more focused clinical trials that are amenable to enrollment. Here we report three children with classic FOP who had recalcitrant flare-ups of the back and who had been treated with an O4 regimen of imatinib. In all three children, fewer flare-ups, decreased swelling and improved function with activities of daily living were reported by the parents and treating physician when the children were "on" imatinib than when they were "off" imatinib. The median time to improvement on imatinib was 2-3 weeks. The anecdotal O4 experience with imatinib reported here in three children with FOP who had recalcitrant flare-ups of the back supports the design of a brief placebo controlled trial to assess the potential efficacy of imatinib in reducing the symptoms in children with refractory flare-ups of FOP. A tool to prospectively measure and quantitate flare-up symptoms is presently being developed and validated and will be used for such a study.

Emotional response inhibition to self-harm stimuli interacts with momentary negative affect to predict nonsuicidal self-injury urges.

The current study investigated whether impaired emotional response inhibition to self-harm stimuli is a risk factor for real-time nonsuicidal self-injury (NSSI) urges. Participants were 60 university students with a history of repetitive NSSI. At baseline, participants completed an emotional stop-signal task assessing response inhibition to self-harm stimuli. Participants subsequently completed an ecological momentary assessment protocol in which they reported negative affect, urgency, and NSSI urge intensity three times daily over a ten-day period. Impaired emotional response inhibition to self-harm stimuli did not evidence a main effect on the strength of momentary NSSI urges. However, emotional response inhibition to self-harm images interacted with momentary negative affect to predict the strength of real-time NSSI urges, after adjusting for emotional response inhibition to neutral images. Our findings suggest that emotional response inhibition deficits specifically to self-harm stimuli may pose vulnerability for increased NSSI urge intensity during real-time, state-level negative affect.

Real-time monitoring of the associations between self-critical and self-punishment cognitions and nonsuicidal self-injury.

The Defective Self Model of nonsuicidal self-injury (NSSI) proposes that some people engage in NSSI to punish themselves and/or to respond to self-critical cognitions. Although there is a growing body of research to support this theory, there has been a lack of ecologically valid approaches employed to critically examine its tenets. The current study aimed to fill this gap in the literature. A sample of 64 undergraduates with a history of repetitive NSSI were recruited and completed an ecological momentary assessment (EMA) protocol. At baseline, participants completed trait measures of self-criticism and self-punishment cognitions. Over the EMA period, participants reported their experience of self-critical and self-punitive cognitions, and NSSI urge intensity three times daily. Our between-persons level findings suggest that trait and aggregated state self-punishment, but not self-critical cognitions, predict NSSI urges experienced over the EMA period. Our findings additionally provide evidence that both momentary self-critical and self-punishment cognitions are concomitantly and prospectively associated with NSSI urge intensity as measured in real-time and modeled at a within-persons level. However, after adjusting for concurrent NSSI urge intensity in prospective models, these within-persons level findings do not hold. Nevertheless, our findings provide greater support for the Defective Self Model of NSSI.

The role of reward sensitivity and childhood maltreatment in predicting nonsuicidal self-injury.

OBJECTIVE: Findings from prior research on reward sensitivity in nonsuicidal self-injury (NSSI) have been mixed. Childhood maltreatment is an independent risk factor for NSSI and for hyposensitivity to rewards. This study aimed to disentangle the role of reward sensitivity as a predictor of NSSI for those with an elevated severity of childhood maltreatment. METHOD: In a diverse undergraduate sample (N = 586), trait reward sensitivity (i.e., behavioral approach system subscales) and the severity of maltreatment were assessed as predictors of a lifetime history of NSSI. In a subset of this sample (n = 51), predictors of NSSI urge intensity were measured using ecological momentary assessment. RESULTS: Individuals with elevated maltreatment who reported less positive responsiveness to rewards were more likely to have a lifetime history of NSSI. Those with elevated maltreatment who reported a lower likelihood to approach rewards experienced more intense NSSI urges across the ten-day observation period. However, those with elevated maltreatment who reported a greater likelihood to approach rewards experienced less intense NSSI urges. CONCLUSIONS: The role of reward sensitivity as a cognitive risk factor for NSSI varies depending on childhood maltreatment history. Findings indicate that, for those with elevated maltreatment, hypersensitivity to approaching rewards may decrease risk for NSSI urges.

Functions of Non-Suicidal Self-Injury in Late Adolescence: A Latent Class Analysis.

This study employed latent class analysis utilizing an array of features of non-suicidal self-injury (NSSI) in order to identify distinct subgroups of self-injurers. Participants were 359 undergraduates with NSSI history. Indicator variables were lifetime and last year frequency rates, number of methods, scarring, pain during self-injury, and functions of NSSI. Analyses yielded mild/experimental NSSI, moderate NSSI, moderate multiple functions NSSI, and severe NSSI groups, endorsing low, moderate, moderate multiple functions, and high frequencies of self-injury and presence of functions, respectively. Following class assignment, groups differed on self-esteem, social support and belongingness, internalizing symptoms, suicidal ideation and behaviors, and additional NSSI constructs. These subtype analyses emphasize matching phenotypes of NSSI to specific interventions considering dimensions of clinical functioning.

Social anxiety and interpersonal stress generation: the moderating role of interpersonal distress.

BACKGROUND AND OBJECTIVES: Existing models of social anxiety scarcely account for interpersonal stress generation. These models also seldom include interpersonal factors that compound the effects of social anxiety. Given recent findings that two forms of interpersonal distress, perceived burdensomeness and thwarted belongingness, intensify social anxiety and cause interpersonal stress generation, these two constructs may be especially relevant to examining social anxiety and interpersonal stress generation together. DESIGN: The current study extended prior research by examining the role of social anxiety in the occurrence of negative and positive interpersonal events and evaluated whether interpersonal distress moderated these associations. METHODS: Undergraduate students (N = 243; M = 20.46 years; 83% female) completed self-report measures of social anxiety, perceived burdensomeness, and thwarted belongingness, as well as a self-report measure and clinician-rated interview assessing negative and positive interpersonal events that occurred over the past six weeks. RESULTS: Higher levels of social anxiety were associated only with a higher occurrence of negative interpersonal dependent events, after controlling for depressive symptoms. This relationship was stronger among individuals who also reported higher levels of perceived burdensomeness, but not thwarted belongingness. CONCLUSIONS: It may be important to more strongly consider interpersonal stress generation in models of social anxiety.

Recording routine forensic mental health evaluations should be a standard of practice in the 21st century.

The standard of practice for forensic interviews in criminal and delinquency cases, other than those conducted as part of brief preliminary screening evaluations or in emergency situations, should include a digital recording requirement. This standard should be adopted because of the greater availability of, and familiarity with, recording technology on the part of mental health professionals, the greater use and proven effectiveness of recording in other contexts of the criminal justice system, and the improvement in court presentation and accuracy of judicial determinations involving forensic assessments that recording will provide. The experience of practitioners with recording since professional associations last studied the issue should be taken into account, as informal data suggest it has been positive. Unfortunately, the legal system is unlikely to prompt this advance without its reconsideration by the forensic mental health professions, because current constitutional jurisprudence does not require recording and effectively makes it contingent upon request by examiners. Forensic evaluators thus have a valuable opportunity to educate the legal system on the utility and importance of this key reform, and so should adopt it as a best practice.

Early clinical observations on the use of imatinib mesylate in FOP: A report of seven cases.

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is an ultrarare genetic disorder of progressive, disabling heterotopic ossification (HO) for which there is presently no definitive treatment. Research studies have identified multiple potential targets for therapy in FOP, and novel drug candidates are being developed for testing in clinical trials. A complementary approach seeks to identify approved drugs that could be re-purposed for off-label use against defined targets in FOP. One such drug is imatinib mesylate, a tyrosine kinase inhibitor originally developed for use in patients with chronic myeloid leukemia (CML). Imatinib has the desirable effect of attacking multiple targets involved in the early hypoxic and inflammatory stages of FOP flare-ups, including HIF1-α, PDGFRα, c-KIT, and multiple MAP kinases. RESULTS: Based on compelling biologic rationale, strong preclinical data, and a favorable safety profile, imatinib has been prescribed on an off-label basis in a non-trial setting in seven children with continuous FOP flare-ups, predominantly in the axial regions, and which were not responsive to standard-of-care regimens. Anecdotal reports in these seven isolated cases document that the medication was well-tolerated with a ubiquitous reported decrease in the intensity of flare-ups in the six children who took the medication. CONCLUSIONS: These early clinical observations support the implementation of clinical trials in children with uncontrolled FOP flare-ups to determine if imatinib may ameliorate symptoms or alter the natural history of this debilitating and life-threatening disease.

The supreme court and the sentencing of juveniles in the United States: reaffirming the distinctiveness of youth.

The US Supreme Court has set 2 key constitutionally based limits to punishment of juveniles; a bar on the imposition of the death penalty for crimes committed by juveniles and of life imprisonment without possibility of parole for juveniles who commit nonhomicide offenses. Both decisions held that these penalties were disproportionate given juveniles' distinctive characteristics. The Court's adoption of a developmental model of culpability may produce future challenges to lengthy juvenile sentences, broad provisions allowing transfer of juveniles for trial as adults, and even possibly to younger juveniles'competence to stand trial.

Educating residents in behavioral health care and collaboration: comparison of conventional and integrated training models.

PURPOSE: To determine whether former pediatric residents trained using a model of integrated behavioral health (BH) care in their primary care continuity clinics felt more comfortable managing BH care and better prepared to collaborate with BH professionals than did peers from the same residency who trained in clinics with a conventional model of BH care. METHOD: University of Rochester School of Medicine and Dentistry pediatric residents were assigned to one of two continuity clinic sites. At one site, psychology fellows and faculty were integrated into the clinic teams in the mid-1990s. At the other, conventional patterns of consultation and referral continued. In 2004, the authors surveyed 245 alumni (graduated 1989-2003) about their experiences and their comfort with providing BH care and collaborating with BH providers in their current practice. RESULTS: A total of 174 alumni (71%) responded. There were significant differences between graduates who trained in the two models. Those who trained in the integrated model were significantly more likely than others to report that they had consulted or planned treatment with a BH provider during residency and to report that their continuity clinic helped prepare them to collaborate with BH providers. They were somewhat more likely to believe that their overall residency training prepared them to manage BH issues in their current practice. CONCLUSIONS: These findings suggest that an integrated training environment, described in detail in the companion article in this issue, can enhance pediatric resident education in the management of BH problems and collaboration with BH specialists.

Educating residents in behavioral health care and collaboration: integrated clinical training of pediatric residents and psychology fellows.

Pediatric residency practices face the challenge of providing both behavioral health (BH) training for pediatricians and psychosocial care for children. The University of Rochester School of Medicine and Dentistry and Rochester General Hospital developed a joint training program and continuity clinic infrastructure in which pediatric residents and postdoctoral psychology fellows train and practice together. The integrated program provides children access to BH care in a primary care setting and gives trainees the opportunity to integrate collaborative BH care into their regular practice routines. During 1998-2008, 48 pediatric residents and 8 psychology fellows trained in this integrated clinical environment. The program's accomplishments include longevity, faculty and fiscal stability, sustained support from pediatric leadership and community payers, the development in residents and faculty of greater comfort in addressing BH problems and collaborating with BH specialists, and replication of the model in two other primary care settings. In addition to quantitative program outcomes data, the authors present a case example that illustrates how the integrated program works and achieves its goals. They propose that educating residents and psychology trainees side by side in collaborative BH care is clinically and educationally valuable and potentially applicable to other settings. A companion report published in this issue provides results from a study comparing the perceptions of pediatric residents whose primary care continuity clinic took place in this integrated setting with those of residents from the same pediatric residency who had their continuity clinic training in a nonintegrated setting.

A blood lead benchmark for assessing risks from childhood lead exposure.

Lead exposure is an insidious problem, causing subtle effects in children at low exposure levels where clinical signs are not apparent. Although a target blood lead concentration (Pb(B)) of ten micrograms per deciliter (10 microg/dL) has been used as the basis for environmental decision-making in California for nearly two decades, recent epidemiologic evidence suggests a relationship between cognitive deficits and Pb(B) at concentrations < 10 microg/dL. Based on a published meta-analysis of children's IQ scores and their blood lead concentrations, we developed a new blood lead benchmark: an incremental increase in blood lead concentration (DeltaPb(B)) of 1 microg/dL, an increase that we estimate could decrease the IQ score in an average school child in California by up to one point. Although there is no evidence to date for a threshold for the neurobehavioral effects of lead, a one-point IQ decrement was chosen to represent a de minimus change. To safeguard the intellectual potential of all children, additional efforts to reduce or eliminate multiple-source exposures to lead are warranted.

Munchausen Syndrome by Proxy: a pediatrician's observations.

Munchausen Syndrome by Proxy (MSP) is a disturbing diagnosis that should be considered when persistent signs and symptoms defy adequate explanation despite extensive testing. Insistence by a parent (often mother) that more, and particularly invasive investigations be pursued, should serve as a warning sign that MSP might be present. The primary care provider who has an existing, over-time, relationship with the child and family is in an important position to raise the question of MSP because this professional may be able to recognize larger dynamics at play between child and family that are less apparent to subspecialists who are focused on a narrow aspect of the evaluation. A confounding element to identifying MSP can also be at play when parent(s) have become proficient in the jargon and technical communication with which professionals on the healthcare team are most comfortable. This easily occurs in cases of MSP both because frequent hospitalizations offer ample opportunity for the articulate and inquisitive parent to pick up the ways of "medical-speak," and because the World Wide Web provides countless and effortlessly accessible sources of disease related information (albeit not always accurate or relevant to the diagnostic dilemma in question). An additional complicating factor in posing a risk for MSP is the child with a chronic illness, or one whose neonatal course has served to label the child as vulnerable.

The growing admissibility of expert testimony by clinical social workers on competence to stand trial.

Expert testimony by clinical social workers concerning a criminal defendant's competence to stand trial has increasingly been admitted in certain state courts over the past two decades, yet most state laws still require that court-appointed competence evaluators be psychiatrists or psychologists. Pressure to admit social workers' testimony will come from social workers' increasing role in diagnosis and treatment of mental disorders. The evolution of forensic assessment instruments that permits greater transparency in competence evaluation and facilitates training, and the standardization of forensic evaluation in general, support greater use of clinical social workers as competence evaluators. A list of proposed qualifications for competence evaluators is developed from recent criticism of evaluation shortcomings, and the article describes how social workers could help address these problems. Through review of representative case precedents, comparison of educational and credentialing practices of clinical social workers and psychologists, and assessment of limited quality data on forensic assessments across disciplines, the article proposes that the principal determinant of qualifications to testify as a competence expert should be advanced training, experience, and credentialing in the specific skills related to competence evaluation rather than professional designation.

The diagnostic significance of soluble CD163 and soluble interleukin-2 receptor alpha-chain in macrophage activation syndrome and untreated new-onset systemic juvenile idiopathic arthritis.

OBJECTIVE: Macrophage activation syndrome is characterized by an overwhelming inflammatory reaction driven by excessive expansion of T cells and hemophagocytic macrophages. Levels of soluble interleukin-2 receptor alpha (sIL-2Ralpha) and soluble CD163 (sCD163) may reflect the degree of activation and expansion of T cells and macrophages, respectively. This study was undertaken to assess the value of serum sIL-2Ralpha and sCD163 in diagnosing acute macrophage activation syndrome complicating systemic juvenile idiopathic arthritis (JIA). METHODS: Enzyme-linked immunosorbent assay was used to assess sIL-2Ralpha and sCD163 levels in sera from 7 patients with acute macrophage activation syndrome complicating systemic JIA and 16 patients with untreated new-onset systemic JIA. The results were correlated with clinical features of established macrophage activation syndrome, including ferritin levels. RESULTS: The median level of sIL-2Ralpha in the patients with macrophage activation syndrome was 19,646 pg/ml (interquartile range [IQR] 18,128), compared with 3,787 pg/ml (IQR 3,762) in patients with systemic JIA (P = 0.003). Similarly, the median level of sCD163 in patients with macrophage activation syndrome was 23,000 ng/ml (IQR 14,191), compared with 5,480 ng/ml (IQR 2,635) in patients with systemic JIA (P = 0.017). In 5 of 16 patients with systemic JIA, serum levels of sIL-2Ralpha or sCD163 were comparable with those in patients with acute macrophage activation syndrome. These patients had high inflammatory activity associated with a trend toward lower hemoglobin levels (P = 0.11), lower platelet counts, and significantly higher ferritin levels (P = 0.02). Two of these 5 patients developed overt macrophage activation syndrome several months later. CONCLUSION: Levels of sIL-2Ralpha and sCD163 are promising diagnostic markers for macrophage activation syndrome. They may also help identify patients with subclinical macrophage activation syndrome.

Chronic arthritis in adolescence.

Musculoskeletal complaints, and joint pain in particular, are common symptoms among adolescents presenting to primary care providers. In this article, the distinction between arthralgia and arthritis is described, and important inflammatory arthropathies seen in teenagers are addressed. The current nomenclature of juvenile idiopathic arthritis is used to address each of the major clinical entities that account for chronic arthritis in teens, including oligoarthritis, polyarthritis, systemic arthritis, psoriatic arthritis, and spondyloarthropathy. Diagnostic criteria, important comorbidities, and principles of management are summarized with identification of antiinflammatory, immunosuppressive, and cytokine-specific biological agents and their relative uses. Other categories of chronic arthritis are also discussed, including infection-associated reactive arthritis, Lyme disease, joint disease of inflammatory bowel disease, as well as chronic arthritis as a dimension of other autoimmune diseases. In addition to the biomedical dimension of these disorders, the psychological impact and developmental context of persistent pain and musculoskeletal abnormality in adolescents are commented on.