Juvenile dermatomyositis resembling late-stage Degos disease with gastrointestinal perforations successfully treated with combination of cyclophosphamide and rituximab: case-based review.

Dermatomyositis (DM) is a multi-system disease that results in chronic inflammation principally of the skin and striated muscle. Small blood vessel injury in the GI tract has been described in dermatomyositis, manifesting as bleeding, ulceration, pneumatosis intestinalis, and ultimately perforation. Recent histopathological studies have shown deposits in the capillaries of the skin, gastrointestinal tract, and brain of patients with dermatomyositis similar to that found in patients with Degos disease, suggesting these disease processes are closely related or represent varying degrees of severity on the same pathologic spectrum. We report a case of juvenile dermatomyositis (JDM) resembling late-stage Degos disease with gastrointestinal perforations successfully treated with combination rituximab and cyclophosphamide therapy. We systematically reviewed the literature detailing the medical and surgical treatments for gastrointestinal perforation in dermatomyositis, Degos-like dermatomyositis, and Degos disease. In addition to our case, as of October 2019, we identified 36 cases describing gastrointestinal perforation in patients with underlying dermatomyositis, 5 cases of Degos-like dermatomyositis and 17 cases of idiopathic Degos disease. Corticosteroid therapy was used widely for dermatomyositis and Degos-like dermatomyositis, while antiplatelet and anticoagulant medications were chiefly used for patients with idiopathic Degos disease. However, there were no cases that detailed the successful treatment of dermatomyositis or Degos disease with gastrointestinal perforation with rituximab alone or combined with cyclophosphamide. We report that rituximab, in combination with cyclophosphamide, can be used as a novel adjunctive therapy to successfully treat dermatomyositis with Degos-like gastrointestinal perforation.

Peptide inhibitor of complement C1 modulates acute intravascular hemolysis of mismatched red blood cells in rats.

BACKGROUND: Acute hemolytic transfusion reactions have a broad clinical presentation from mild and transitory signs and symptoms to shock, disseminated intravascular coagulation, renal failure, and death. We have recently developed a rat model of acute intravascular hemolysis showing that the classical complement pathway mediates antibody-dependent hemolysis. The objective of this study was to evaluate the role of the classical pathway inhibitor peptide inhibitor of complement C1 (PIC1) in this animal model. STUDY DESIGN AND METHODS: Male Wistar rats received a 15% transfusion of human red blood cells (RBCs) and blood was isolated from the animals up to 120 minutes. Animals received PIC1 either 2 minutes before or 0.5 minutes after transfusion. Sham-, vehicle-, and cobra venom factor (CVF)-treated animals were used as control groups with a subset of rats also receiving an equivalent dose of intravenous immunoglobulin (IVIG) before transfusion. Blood was analyzed for transfused RBC survival by flow cytometry and free hemoglobin (Hb) in isolated plasma by spectrophotometry. RESULTS: Vehicle-treated rats showed decreased human RBC survival and increased free Hb as expected. Rats receiving PIC1 before transfusion showed increased human RBC survival and decreased Hb similar to CVF-treated rats. Notably, rats receiving PIC1 after initiation of transfusion showed similar decreases in hemolysis as animals receiving PIC1 before transfusion. Compared to IVIG and saline controls, PIC1-treated animals demonstrated decreased hemolysis and protection from acute kidney injury. CONCLUSIONS: These results demonstrate that PIC1 has efficacy in an animal model of acute intravascular hemolysis in both prevention and rescue scenarios.

Eosinophil Quantitated Urine Kinetic: A novel assay for assessment of eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic disease that requires long-term medical management and monitoring. The eosinophil count determined during esophageal biopsy remains the gold standard for diagnosis and monitoring of EoE. Although markers of eosinophil degranulation correlate with symptoms, eosinophil counts do not correlate. Development of a noninvasive, cost-effective biomarker of eosinophil activation for the evaluation of EoE is an unmet medical need. OBJECTIVE: To conduct a proof-of-concept study to evaluate the potential for measuring urinary 3-bromotyrosine (3-BT) levels in creatinine normalized urine for quantifying eosinophil degranulation in EoE disease. METHODS: A mass spectrometry-based method of measuring normalized 3-BT levels, the Eosinophil Quantitated Urine Kinetic (EoQUIK), was developed, and proof-of-concept evaluation was performed for patients with EoE (n = 27), atopic controls (n = 24), and nonatopic controls (n = 24). RESULTS: EoQUIK revealed that median normalized 3-BT levels were increased 93-fold in patients with EoE compared with nonatopic controls (P = .01) and increased 13-fold in patients with EoE compared with atopic controls (P = .01). Cutoff thresholds were selected for EoQUIK that yielded a specificity of 100% and a negative predictive value of 100% for nonatopic controls and a specificity of 79% and a negative predictive value of 90% for atopic controls. In a logistic regression model, a urine 3-BT level greater than 20 pg per 400 mg of creatinine increased the odds of a patient having EoE by 4.8 (95% confidence interval, 1.14-20.5; P = .03) when compared with atopic controls after controlling for race and sex. CONCLUSION: These data provide proof of concept that EoQUIK can potentially be a useful noninvasive clinical tool in the evaluation of possible EoE.

Complement inhibition significantly decreases red blood cell lysis in a rat model of acute intravascular hemolysis.

BACKGROUND: Prevention of acute hemolytic transfusion reactions is a worldwide concern. The objective of this study was to develop a simple rat model of complement-mediated acute intravascular hemolysis. STUDY DESIGN AND METHODS: Human AB red blood cells (RBCs) were incubated with complement-sufficient or complement-deficient Wistar rat serum (WRS) in the presence and absence of human RBC antibody in vitro to elucidate the mechanism of hemolysis. To study the role of complement in acute intravascular hemolysis in vivo, Wistar rats were treated either with or without cobra venom factor (CVF) to deplete complement activity. Human AB RBCs were then injected into both groups of rats, followed by serial blood draws up to 2 hours. Venous blood clearance and lysis of transfused RBCs at each time point were measured by flow cytometry and spectrophotometry. RBC sequestration was determined in the liver, spleen, and kidney by immunohistochemistry. RESULTS: In vitro incubation of human RBCs with WRS demonstrated that RBC lysis was mediated via the classical complement pathway and that hemolysis was antibody dependent. Transfusion of human RBCs into rats showed significantly less hemolysis in the CVF group versus untreated group. RBC sequestration in the spleen and liver 2 hours posttransfusion were not quantitatively different between the two groups. CONCLUSIONS: Given the much higher degree of similarity for rat and human complement compared to mice, this simple rat model is ideal for testing novel inhibitors of classical pathway activation for the prevention and treatment of acute intravascular hemolysis.

Infarction of Paratesticular Inflammatory Myofibroblastic Tumor Mimicking Testicular Torsion.

This report describes a 14-year-old male with a rare paratesticular inflammatory myofibroblastic tumor that presented atypically with acute unilateral scrotal pain and swelling. This presentation, which raised suspicion for testicular torsion, contrasts with the typical presentation of a slow-growing scrotal mass. Scrotal exploration revealed an infarcted right testis, demonstrating this locally aggressive tumor can undergo vascular invasion and occlude testicular blood supply. Thus, inflammatory myofibroblastic tumor should be considered in the differential diagnosis when evaluating patients with acute scrotal pain suspicious for testicular infarction.

Peptide inhibition of acute lung injury in a novel two-hit rat model.

Acute lung injury (ALI) often causes severe trauma that may progress to significant morbidity and mortality. ALI results from a combination of the underlying clinical condition of the patient (e.g., inflammation) with a secondary insult such as viral pneumonia or a blood transfusion. While the secondary insult may be variable, the rapidly progressive disease process leading to pulmonary failure is typically mediated by an overwhelming innate immunological or inflammatory reaction driven by excessive complement and neutrophil-mediated inflammatory responses. We recently developed a 'two-hit' ALI rat model mediated by lipopolysaccharide followed by transfusion of incompatible human erythrocytes resulting in complement activation, neutrophil-mediated ALI and free DNA in the blood indicative of neutrophil extracellular trap formation. The objective of this study was to evaluate the role of peptide inhibitor of complement C1 (RLS-0071), a classical complement pathway inhibitor and neutrophil modulator in this animal model. Adolescent male Wistar rats were infused with lipopolysaccharide followed by transfusion of incompatible erythrocytes in the presence or absence of RLS-0071. Blood was collected at various time points to assess complement C5a levels, free DNA and cytokines in isolated plasma. Four hours following erythrocyte transfusion, lung tissue was recovered and assayed for ALI by histology. Compared to animals not receiving RLS-0071, lungs of animals treated with a single dose of RLS-0071 showed significant reduction in ALI as well as reduced levels of C5a, free DNA and inflammatory cytokines in the blood. These results demonstrate that RLS-0071 can modulate neutrophil-mediated ALI in this novel rat model.

Physical and Physiological Determinants of Rock Climbing.

PURPOSE: Rock climbing performance relies on many characteristics. Herein, the authors identified the physical and physiological determinants of peak performance in rock climbing across the range from lower grade to elite. METHODS: Forty four male and 33 female climbers with onsight maximal climbing grades 5a-8a and 5a-7b+, respectively, were tested for physical, physiological, and psychological characteristics (independent variables) that were correlated and modeled by multiple regression and principal component analysis to identify the determinants of rock climbing ability. RESULTS: In males, 23 of 47 variables correlated with climbing ability (P < .05, Pearson correlation coefficients .773-.340), including shoulder endurance, hand and finger strength, shoulder power endurance, hip flexibility, lower-arm grip strength, shoulder power, upper-arm strength, core-body endurance, upper-body aerobic endurance, hamstrings and lower-back flexibility, aerobic endurance, and open-hand finger strength. In females, 10 of 47 variables correlated with climbing ability (P < .05, Pearson correlation coefficients .742-.482): shoulder endurance and power, lower-arm grip strength, balance, aerobic endurance, and arm span. Principal component analysis and univariate multiple regression identified the main explanatory variables. In both sexes, shoulder power and endurance measured as maximum pull-ups, average arm crank power, and bent-arm hang, emerged as the main determinants (P < .01; adjusted R2 = .77 in males and .62 in females). In males, finger pincer (P = .07) and grip strength also had trends (P = .09) toward significant effects. Finally, in test-of-principle training studies, they trained to increase main determinants 42% to 67%; this improved climbing ability 2 to 3 grades. CONCLUSIONS: Shoulder power and endurance majorly determines maximal climbing. Finger, hand, and arm strength, core-body endurance, aerobic endurance, flexibility, and balance are important secondary determinants.

Incompatible erythrocyte transfusion with lipopolysaccharide induces acute lung injury in a novel rat model.

Acute transfusion reactions can manifest in many forms including acute hemolytic transfusion reaction, allergic reaction and transfusion-related acute lung injury. We previously developed an acute hemolytic transfusion reaction rat model mediated by transfusion of incompatible human erythrocytes against which rats have preexisting antibodies resulting in classical complement pathway mediated intravascular hemolysis. In this study, the acute hemolytic transfusion reaction model was adapted to yield an acute lung injury phenotype. Adolescent male Wistar rats were primed in the presence or absence of lipopolysaccharide followed by transfusion of incompatible erythrocytes. Blood was collected at various time points during the course of the experiment to determine complement C5a levels and free DNA in isolated plasma. At 4 hours, blood and lung tissue were recovered and assayed for complete blood count and histological acute lung injury, respectively. Compared to sham animals or animals receiving increasing amounts of incompatible erythrocytes (equivalent to a 15-45% transfusion) in the absence of lipopolysaccharide, lungs of animals receiving lipopolysaccharide and a 30% erythrocyte transfusion showed dramatic alveolar wall thickening due to neutrophil infiltration. C5a levels were significantly elevated in these animals indicating that complement activation contributes to lung damage. Additionally, these animals demonstrated a significant increase of free DNA in the blood over time suggestive of neutrophil extracellular trap formation previously associated with transfusion-related acute lung injury in humans and mice. This novel 'two-hit' model utilizing incompatible erythrocyte transfusion in the presence of lipopolysaccharide yields a robust acute lung injury phenotype.

Microdebrider vs electrocautery: a comparison of tonsillar wound healing histopathology in a canine model.

OBJECTIVE: To evaluate tonsillar wound healing histopathology in a canine model following microdebrider intracapsular and electrocautery tonsillectomy techniques. STUDY DESIGN: Randomized, controlled, single-blinded, paired comparison of histopathology. SUBJECTS AND METHODS: Twelve beagles underwent tonsillectomies by microdebrider on one side and electrocautery on the other. Punch biopsies were taken of the tonsillar fossae on postoperative days 3, 9, and 20. Specimens were graded with a novel mucosal wound healing scale (inter-rater reliability, r = 0.83) and appropriate statistical analysis performed. RESULTS: Combined mucosal wound healing scale scores showed significantly faster healing on the microdebrider side when compared to the electrocautery side on postoperative day 3 and day 9 (P < 0.05), which equalized by day 20. CONCLUSION: In a canine model of tonsillar wound healing, microdebrider intracapsular tonsillectomy produced significantly faster healing than electrocautery tonsillectomy in the early postoperative course. The "biologic dressing" theory of intracapsular tonsillectomy wound healing may account for observed differences in healing and suggests a mechanism for improved clinical outcomes.

A 1-Year-Old with Mycobacterium tuberculosis Endocarditis with Mass Spectrometry Analysis of Cardiac Vegetation Composition.

In this study, we report the first case of Mycobacterium tuberculosis endocarditis in an immunocompetent child born in the United States. Mass spectrometry of the vegetation identified coagulation, humoral immune proteins, neutrophil granule proteins, and histones. Few neutrophils on histopathology suggest that neutrophil extracellular traps may contribute to tuberculous endocardiac mass formation.

Juvenile xanthogranuloma of the tympanic membrane: a case report.

Juvenile xanthogranuloma (JXG) is a benign, non-Langerhans cell histiocytic lesion that generally affects infants and children. These lesions characteristically appear as a solitary, yellow, cutaneous nodule of the head, neck, or trunk. Subcutaneous and extracutaneous forms can involve the gastrointestinal tract, kidney, lung, gonads, pericardium, central nervous system, temporal bone, larynx, and eye. We describe the clinical presentation, imaging, histochemical findings, and management of a solitary JXG of the tympanic membrane in a 17-month-old girl. The patient underwent surgical resection and was without disease several months following surgery and reconstruction of the defect. To the best of our knowledge, this is the first reported case of a JXG of the tympanic membrane.

Comparison of FT4 with log TSH on the Abbott Architect ci8200: Pediatric reference intervals for free thyroxine and thyroid-stimulating hormone.

BACKGROUND: We evaluated the clinical validity of serum FT4 measurements by assessing its correlation with log TSH. To provide pediatric reference intervals (representative ranges) for FT4, and TSH on the Architect ci8200 integrated system. METHODS: This population-based study encompassed 6023 children (3369 females and 2654 males). The percentile and Hoffmann approaches for obtaining reference intervals on these analytes were also compared. RESULTS: FT4 correlation with log TSH was poor ( r=0.010 for males and 0.050 for females). Reference intervals were established. TSH and FT4 did not show a significant sex difference; moreover, the intervals decreased with age for FT4 and TSH. CONCLUSIONS: Whereas in a previous study ultrafiltration tandem mass spectrometry yielded a correlation of r=0.90 for FT4 vs. log TSH this present study reveals a poor FT4 vs. log TSH correlation in the pediatric population studied and indicates the FT4 immunoassay conducted on the Abbott Architect ci8200 is less useful clinically than might have been expected. Reference intervals using the Hoffmann approach for pediatric in- and out-patients compare well with previously published results utilizing the percentile approach.

Clinicopathologic features of histiocytic lesions following ALL, with a review of the literature.

We describe the clinicopathologic features of 15 patients who had histiocytic lesions that followed acute lymphoblastic leukemia (ALL). Twenty-one separate histiocytic lesions were evaluated that covered a wide spectrum, some conforming to the usual categories of juvenile xanthogranulomas (5), Langerhans' cell histiocytosis (1), Langerhans' cell sarcoma (4), Rosai-Dorfman disease (1), and histiocytic sarcoma (4). Most were atypical for the category by histology, phenotype, or abnormally high turnover rate. Seven low-grade lesions defied easy categorization and were characterized only as "atypical histiocytic lesion" following ALL. For those evaluated, the molecular signature of the prior leukemia was present in the histiocytic lesion. In 3 of 15 patients, the leukemia and histiocytic lesion shared immunoglobulin H or monoclonal TCR gene rearrangements and, in 4 of 15 patients, clonal identity was documented by fluorescence in situ hybridization. Four patients died of progressive disease, 3 of whom had histiocytic sarcoma and 1 who had an atypical lesion. One patient died of recurrent ALL. The other 10 patients are alive, 7 after recurrences and treatment with surgery and/or chemotherapy. The post-ALL lesions are more aggressive than their native counterparts, but despite the demonstration of the presence of the leukemia signature in 7 of 15 patients, the prognosis is generally favorable, except for patients with histiocytic sarcoma. It remains unclear whether the histiocytic lesions arise as a line from the original ALL or whether transdifferentiation is involved.

Aggressive Digital Papillary Adenocarcinoma in a 15-year-old Female.

Aggressive digital papillary adenocarcinoma is a rare neoplasm of eccrine sweat gland origin that typically presents as a mass on a finger, toe, or the adjacent skin. Less than 100 cases have been reported. The majority of these cases are described in males in their fifth to seventh decade. We report a case of an aggressive digital papillary adenocarcinoma of the right second toe in a 15-year-old white female. A metastatic work-up, computed tomography of the chest, abdomen, pelvis, and a bone scan, was negative. The patient underwent amputation of the right second toe through the metatarsophalangeal joint. Two sentinel lymph nodes were biopsied and found to be negative for metastatic disease. One year after surgery the patient has no evidence of disease recurrence. To our knowledge, this is the youngest reported case of an aggressive digital papillary adenocarcinoma.

Pacman dysplasia: a lethal skeletal dysplasia with variable radiographic features.

BACKGROUND: Punctate or stippled cartilaginous calcifications are associated with many conditions, including chromosomal, infectious, endocrine, and teratogenic etiologies. Some of these conditions are clinically mild, while others are lethal. Accurate diagnosis can prove instrumental in clinical management and in genetic counseling. OBJECTIVE: To describe the diagnostic radiographic features seen in Pacman dysplasia, a distinct autosomal recessive, lethal skeletal dysplasia. MATERIALS AND METHODS: We present the fourth reported case of Pacman dysplasia and compare the findings seen in our patient with the three previously described patients. RESULTS: Invariable and variable radiographic findings were seen in all four cases of histologically proven Pacman dysplasia. CONCLUSION: Pacman dysplasia presents both constant and variable diagnostic radiographic features.