Treacher Collins syndrome with novel ophthalmic findings and visceral anomalies.
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Adult↗
Biomedical subjects
E Ruchelli
Publications and source records attributed to E Ruchelli.
Retropharyngeal aberrant thymus.
INTRODUCTION: Upper airway obstruction from a retropharyngeal mass requires urgent evaluation. In children, the differential diagnosis includes infection, trauma, neoplasm, and congenital abnormalities. Aberrant cervical thymic tissue, although occasionally observed on autopsy examination, is rarely clinically significant. We present the case of an infant with respiratory distress attributed to aberrant thymic tissue located in the retropharyngeal space. CASE: A 6-week-old infant was brought to the emergency department for evaluation of stridor associated with periodic episodes of cyanosis. Lateral neck radiograph revealed widening of the retropharyngeal soft tissues. The patient's symptoms did not improve with intravenous ampicillin-sulbactam. Magnetic resonance imaging (MRI) performed on the seventh day of hospitalization revealed a retropharyngeal mass that extended to the carotid space. The mass was easily resected using an intraoral approach. Microscopic examination demonstrated thymic tissue. A normal thymus was also observed in the anterior mediastinum on MRI. The patient recovered uneventfully and had no further episodes of stridor or cyanosis. DISCUSSION: Aberrant cervical thymic tissue may be cystic or solid. Cystic cervical thymus is more common, and 6% of these patients present with symptoms of dyspnea or dysphagia. Aberrant solid cervical thymus usually presents as an asymptomatic anterior neck mass. This case is unusual in that solid thymic tissue was located in the retropharynx, a finding not previously reported in the English literature. Additionally, the patient presented in acute respiratory distress, and the diagnosis was confounded by the presence of mild laryngomalacia. In retrospect, our patient likely had symptoms of intermittent upper airway obstruction since birth. The acute respiratory distress at presentation was likely the result of laryngomalacia exacerbated by the presence of aberrant thymic tissue and a superimposed viral infection. Aberrantly located thymic tissue arises as a consequence of migrational defects during thymic embryogenesis. The thymus is a paired organ derived from the third and, to a lesser extent, fourth pharyngeal pouches. After its appearance during the sixth week of fetal life, it descends to a final position in the anterior mediastinum, adjacent to the parietal pericardium. Aberrant thymic tissue results when this tissue breaks free from the thymus as it migrates caudally. Therefore, aberrant thymic tissue may be found in any position along a line from the angle of the mandible to the sternal notch, and in the anterior mediastinum to the level of the diaphragm. In an autopsy study of 3236 children, abnormally positioned thymic tissue was found in 34 cases (1%). The aberrant thymus was most often located near the thyroid gland (n = 19 cases) but was also detected lower in the anterior neck (n = 6 cases), higher in the anterior neck (n = 8 cases), and at the left base of the skull (n = 1 case). The presence of thymic tissue in the retropharyngeal space in our patient is more unusual given the typical embryologic origin and descent of the thymus in the anterior neck to the mediastinum. Children with aberrant thymus may have associated anomalies. Twenty-four of 34 children (71%) with aberrant thymus detected at autopsy had features consistent with DiGeorge syndrome, and only 5 of the remaining 10 patients had a normal mediastinal thymus present. Our patient had normal serum calcium levels after excision and a mediastinal thymus was visualized on MRI. Biospy is required for diagnosis of cervical thymus and should also be considered to exclude other causes. MRI is helpful in delineating the presence, position, and extent of thymic tissue. Immunologic sequelae or recurrence after resection of an aberrant cervical thymus has not been reported.
Airway Obstruction↗
Successful reversal of recalcitrant hepatic allograft rejection by photopheresis.
Extracorporeal photopheresis (ECP) is an immunologic modality that has shown efficacy in the treatment of clonal T-cell diseases, including Sézary syndrome and allograft rejection. In this case report, we expand on this observation to include recalcitrant hepatic allograft rejection. A 14-year-old boy with hepatic allograft rejection refractory to high-dose corticosteroid and lymphocytolytic therapy was treated with 4 sessions of ECP over a 6-week period. After 2 sessions, a liver biopsy showed complete reversal of acute cell-mediated rejection. No opportunistic infections or other adverse events were noted. Photopheresis appears to be a safe and effective modality for the treatment of refractory hepatic allograft rejection.
Adolescent↗
Serum hyaluronan and its association with unfavorable histology and aggressiveness of heterotransplanted Wilms' tumor.
BACKGROUND/PURPOSE: The sera and urine of children with Wilms' tumor (WT) often contain increased concentrations of hyaluronan (HA). The authors developed a heterotransplant model to investigate whether serum HA concentrations could predict the histology and progression of WT. METHODS: Random portions of 8 human WT specimens (7 favorable and 1 unfavorable histology findings) were heterotransplanted into the flanks of severe combined immunodeficient (SCID) mice. After 6 to 20 weeks of observation, animals were killed, and serum HA concentrations, tumor histology, and local invasion were determined. RESULTS: Sera of mice supporting tumor growth had a median HA concentration of 9,379 microg/L (range, 459 to 3,206,176 microg/L) compared with a median HA concentration of 416 microg/L (range, 204 to 782 microg/L) in animals not supporting tumor growth. The highest serum HA concentrations were detected in animals harboring unfavorable histology blastemal-predominant tumors, whereas animals supporting favorable histology epithelial- and stromal-predominant tumors had the lowest serum HA concentrations. In association with markedly increased serum HA, undifferentiated blastemal tumors showed significantly greater growth rates than the more differentiated epithelial or stromal tumors. Additionally, serum HA concentrations were greater in mice with invasive as compared with noninvasive tumors for each histological type. Complete resection of established tumors also resulted in the return of serum HA to preheterotransplant concentrations. Identification of tumor progression was further tested in SCID mice receiving subcutaneous flank injections of the human WT cell line, SK-NEP-1. Significantly greater serum HA concentrations again corresponded with more rapid growth rates and invasiveness. CONCLUSIONS: Serum HA concentrations predict the growth, invasion, and unfavorable histology findings of WT in a heterotransplant model. The authors further speculate that HA may foster an environment conducive to WT aggressiveness.
Animals↗
Colonic inflammation found at diagnosis of juvenile retention polyps in pediatric patients.
OBJECTIVE: The finding of colonic inflammation concurrently with a juvenile retention polyp (JRP) may have prognostic value. However, the significance of abnormal mucosal histology with JRP has not been evaluated. We evaluated the significance of mucosal histology at the time of JRP removal with respect to future development of inflammatory bowel disease (IBD) and polyp recurrence. METHODS: The medical records of patients who had an endoscopic polypectomy performed at the Children's Hospital of Philadelphia (CHOP) from 1/1/87 through 4/30/98 were retrospectively reviewed. RESULTS: JRP was histologically identified in 96 patients. A total of 54 patients had colonic mucosal biopsies: 30 (55.6%) had normal histology and 24 (44.4%) had colitis. Of the 24 patients with colitis, 14 patients (58.3%) had inflammation at the polyp site. Twelve of these patients had additional inflammation elsewhere in the colon. Nine (37.5%) had inflammation elsewhere in the colon; however, biopsies around the polyp site were not obtained. One patient with inflammation did not have the location of the polyp documented. Four patients (16.7%) had IBD at the time of polypectomy; two were diagnosed prior and two coincident with JRP. None have subsequently been diagnosed with IBD. There was no difference in polyp recurrence between those with or without inflammation (16.7% [4/24] vs 10.0% [3/30]). The mean follow-up period was 72.4 months (range, 5-142 months). CONCLUSIONS: In our experience, histological mucosal inflammation is a common finding with JRP. This inflammation may be a precursor for the development of JRP but has no predictive value for polyp recurrence. This colitis does not seem to be associated with IBD.
Adolescent↗
Pneumonia in infants and children: radiological-pathological correlation.
The radiographic characteristics of pulmonary infection in children are many and varied. Although typical patterns are helpful in diagnosis, clinical and laboratory evaluation provide important diagnostic information. An understanding of the basic pathophysiology of infection and an appreciation of the anatomy of the child's growing lung help provide clearer, insightful, and more accurate radiological interpretation.
Child↗
Langerhans' cell histiocytosis with stool retention caused by a perianal mass.
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Anus Diseases↗
Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids.
BACKGROUND: The histologic appearance of esophageal eosinophils has been correlated with esophagitis and gastroesophageal reflux disease in children. Esophageal eosinophilia that persists despite traditional antireflux therapy may not represent treatment failure, but instead may portray early eosinophilic gastroenteritis or allergic esophagitis. In this study, a series of pediatric patients with severe esophageal eosinophilia who were unresponsive to aggressive antireflux therapy were examined and their clinical and histologic response to oral corticosteroid therapy assessed. METHODS: Of 1809 patients evaluated prospectively over 2.5 years for symptoms of gastroesophageal reflux, 20 had persistent symptoms and esophageal eosinophilia, despite aggressive therapy with omeprazole and cisapride. These patients were treated with 1.5 mg/kg oral methylprednisolone per day, divided into twice-daily doses for 4 weeks. All patients underwent clinical, laboratory, and histologic evaluation before and after treatment. RESULTS: Histologic findings in examination of specimens obtained in pretreatment esophageal biopsies in children with primary eosinophilic esophagitis indicated significantly greater eosinophilia (34.2+/-9.6 eosinophils/high-power field [HPF]) compared with that in children with gastroesophageal reflux disease who responded to medical therapy (2.26+/-1.16 eosinophils/HPF; p < 0.001). After corticosteroid therapy, all but one patient with primary eosinophilic esophagitis had dramatic clinical improvement, supported by histologic examination (1.5 +/-0.9 eosinophils/HPF, p < 0.0001). CONCLUSIONS: Pediatric patients in a series with marked esophageal eosinophilia and chronic symptoms of gastroesophageal reflux disease unresponsive to aggressive medical antire-flux therapy had both clinical and histologic improvement after oral corticosteroid therapy.
Anti-Inflammatory Agents↗
Enteric defensin expression in necrotizing enterocolitis.
Immaturity of local innate defenses has been suggested as a factor involved in the pathophysiology of necrotizing enterocolitis (NEC). The mRNA of enteric human defensins 5 (HD5) and 6 (HD6), antibiotic peptides expressed in Paneth cells of the small intestine, have significantly lower levels of expression in fetal life compared with the term newborn and adult. In the current study, intracellular HD5 was demonstrated by immunohistochemistry at 24 wk of gestation, but at low levels, consistent with findings at the mRNA level. These data suggest that the low level enteric defensin expression, characteristic of normal intestinal development, may contribute to the immaturity of local defense, which predisposes the premature infant to NEC. To test if levels of defensin expression are altered in NEC, specimens from six cases of patients with NEC and five control subjects (four patients with atresia and one with meconium ileus) were analyzed to determine HD5 and HD6 mRNA levels by in situ hybridization. Compared with the control group, the level of enteric defensin expression per Paneth cell assessed by image analysis was increased 3-fold in cases of NEC (p = 0.02, analysis of variance and covariance). In addition, the number of Paneth cells was increased 2-fold in the small intestinal crypts of NEC specimens compared with those of control subjects (p < 0.01, covariance analysis). In healthy tissue, peptide levels within Paneth cells paralleled mRNA levels through development. In tissue from infants with NEC, the steady state level of intracellular peptide was not increased in conjunction with the observed rise in defensin mRNA. A straightforward interpretation of this finding is that HD5 is actively secreted in this setting and the Paneth cells maintain a constant steady state level of intracellular peptide, but the possibility of translational regulation of peptide expression is also consistent with these data. The associations between NEC and enteric defensin expression reported here offer support for future studies to address the role of these endogenous host defense factors in the pathophysiology of this disease.
Adult↗
Heterotaxia in a fetus with campomelia, cervical lymphocele, polysplenia, and multicystic dysplastic kidneys: expanding the phenotype of Cumming syndrome.
We report on a fetus with tetramelic campomelia, polysplenia, multicystic dysplastic kidneys, and cervical lymphocele. This condition is similar to the autosomal recessive condition described by Cumming et al. [1986: Am J Med Genet 25:783-790] and is different from campomelic syndrome. In addition, our case had anomalies not previously described in this condition, including abnormal lung lobation with bilateral left bronchial morphology, dextrocardia, total anomalous pulmonary venous return, a left superior vena cava, and a right aortic arch. The pancreas was short, with absence of the body and tail. These anomalies are similar to those found in the polyasplenia spectrum. We suggest that the syndrome reported by Cumming et al. may be expanded to include polysplenia with heterotaxia and that Cumming syndrome may be considered another autosomal recessive condition associated with a laterality defect.
Abnormalities, Multiple↗
Bronchitis obliterans due to Mycoplasma pneumonia.
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Bronchiolitis Obliterans↗
Acremonium infection of the esophagus.
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Acremonium↗
Human enteric defensins. Gene structure and developmental expression.
Paneth cells, secretory epithelial cells of the small intestinal crypts, are proposed to contribute to local host defense. Both mouse and human Paneth cells express a collection of antimicrobial proteins, including members of a family of antimicrobial peptides named defensins. In this study, data from an anchored polymerase chain reaction (PCR) strategy suggest that only two defensin mRNA isoforms are expressed in the human small intestine, far fewer than the number expressed in the mouse. The two isoforms detected by this PCR approach were human defensin family members, HD-5 and HD-6. The gene encoding HD-6 was cloned and characterized. HD-6 has a genomic organization similar to HD-5, and the two genes have a striking pattern of sequence similarity localized chiefly in their proximal 5'-flanking regions. Analysis of human fetal RNA by reverse transcriptase-PCR detected enteric defensin HD-5 mRNA at 13.5 weeks of gestation in the small intestine and the colon, but by 17 weeks HD-5 was restricted to the small intestine. HD-6 mRNA was detectable at 13.5-17 weeks of gestation in the small intestine but not in the colon. This pattern of expression coincides with the previously described appearance of Paneth cells as determined by ultrastructural approaches. Northern analysis of total RNA from small intestine revealed quantifiable enteric defensin mRNA in five samples from 19 24 weeks of gestation at levels approximately 40-250-fold less than those observed in the adult, with HD-5 mRNA levels greater than those of HD-6 in all samples. In situ hybridization analysis localized expression of enteric defensin mRNA to Paneth cells at 24 weeks of gestation, as is seen in the newborn term infant and the adult. Consistent with earlier morphological studies, the ratio of Paneth cell number per crypt was reduced in samples at 24 weeks of gestation compared with the adult, and this lower cell number partially accounts for the lower defensin mRNA levels as determined by Northern analysis. Low levels of enteric defensin expression in the fetus may be characteristic of an immaturity of local defense, which is thought to predispose infants born prematurely to infection from intestinal microorganisms.
Amino Acid Sequence↗
Epstein-Barr virus-associated hepatic smooth muscle neoplasm in a cardiac transplant recipient.
Host immunosuppression is increasingly recognized as a significant risk factor for the development of a primary neoplasm. Chronic immunosuppressive therapy, as used in organ transplantation, may perturb the immunosurveillance ability of the host, making the patient more susceptible to virus-associated malignancies. We have taken care of a care of a child who received an orthotopic heart transplant and who then developed both a generalized lymphoproliferative disorder and a leiomyoma of the liver a year later. Epstein-Barr virus DNA was detected in a lymph node initially and the hepatic tumor cells subsequently. The former responded to a reduction in the immunosuppressive medications and the latter responded to surgical resection. This is the first report of a hepatic smooth cell neoplasm occurring following cardiac transplant and the development of two sequential Epstein-Barr virus-associated disorders in an immunosuppressed patient.
Child↗
Prenatal diagnosis of a chest wall hamartoma and sternal cleft.
We present the prenatal evaluation and diagnosis of a disorganized chest wall hamartoma with underlying sternal cleft in a family with a prior offspring with the VATER association. The possibility that these conditions are linked to mesodermal defects with a common pathogenic etiology is suggested.
Adult↗
Treatment of pediatric autoimmune enteropathy with tacrolimus (FK506).
Autoimmune enteropathy is characterized by chronic secretory diarrhea, villous atrophy, associated autoantibodies, and a partial response to immunosuppression. Currently available therapy (including steroids and cyclosporine) has resulted in remission only in a subset of patients. We evaluated the effects of tacrolimus (FK506) in patients with autoimmune enteropathy refractory to steroids and cyclosporine. Three patients with diagnosed autoimmune enteropathy who continued to have intractable diarrhea despite treatment with steroids and/or cyclosporine were treated with oral tacrolimus. Despite documented histological villous atrophy and poor absorption of oral cyclosporine, therapeutic tacrolimus levels were easily achieved in all 3 patients. All patients showed clinical improvement as documented by decreased stool output and ability to be weaned off parenteral nutrition; response time ranged from 1 to 4 months after tacrolimus was begun. Histological improvement was noted in all patients, and the small bowel biopsy specimens of 2 of the 3 patients showed a return to normal. All patients have been followed up for at least 6 months and are in clinical remission; 1 has received a bone marrow transplant for underlying immunodeficiency. Tacrolimus is a useful drug in the treatment of autoimmune enteropathy, even in patients who have not responded to steroids or cyclosporine. No long-term follow-up of patients with autoimmune enteropathy treated with tacrolimus is currently available.
Administration, Oral↗
An uncommon presentation of Salmonella.
Salmonella infection can cause appendicitis by direct invasion of the appendix, or can mimic appendicitis by causing mild inflammation of the appendix, ileum, or lymph nodes. Clinical presentation and radiologic and laboratory evaluation may not distinguish the extent of underlying pathology. This case of a child with an atypical presentation of Salmonella who underwent diagnostic laparotomy illustrates the overlap of enteric infections and acute appendicitis. A literature review confirms the variety of clinical scenarios of patients with suspected appendicitis and Salmonella-positive cultures. We conclude that enteric infection should be considered in children with atypical presentations of appendicitis, and that the knowledge that Salmonella can progress to appendicitis should guide management if signs and symptoms of appendicitis develop.
Adolescent↗
Misalignment of pulmonary veins with alveolar capillary dysplasia: affected siblings and variable phenotypic expression.
Misalignment of pulmonary veins with alveolar capillary dysplasia is recognized as a rare cause of persistent pulmonary hypertension of the neonate. Until now, misalignment of pulmonary veins was thought to be a random occurrence, but its appearance in siblings at our institution suggests that there may be a familial predisposition. There have been reports of variable expression and variable severity in this disease; our report describes this variability in family members.
Abnormalities, Multiple↗