Peter C. Rowe

Eosinophilic esophagitis attributed to gastroesophageal reflux: Improvement with an amino acid-based formula☆☆☆

BACKGROUND & AIMS Treatment for gastroesophageal reflux may be ineffective in patients with an eosinophilic infiltration of the esophagus. The aim of this study was to investigate whether unremitting symptoms of gastroesophageal reflux and biopsy abnormalities of the esophagus may be associated with the ingestion of certain foods. METHODS Ten children previously diagnosed with gastroesophageal reflux by standard testing with long-standing symptoms (median, 34.3 months; range, 6-78 months) despite standard antireflux therapies, including Nissen fundoplication in 6 patients, were fed the elemental formulas Neocate or Neocate-1-Plus (Scientific Hospital Supplies Inc., Gaithersburg, MD) for a minimum of 6 weeks. Each child had repeat endoscopy followed by open food challenges. RESULTS While receiving the formulas, patients had either resolution (n = 8) or improvement (n = 2) of symptoms. On follow-up esophageal biopsy, the maximal intraepithelial eosinophil counts decreased significantly before (median, 41; range, 15-100) to after (median, 0.5; range, 0-22) the formula trial (P = 0.005). Other reactive epithelial changes of the esophageal mucosa also improved significantly. All patients redeveloped their previous symptoms on open food challenges. CONCLUSIONS Chronic gastrointestinal symptoms and histological changes of the esophagus unresponsive to standard treatments for gastroesophageal reflux were improved by the use of elemental formulas. Symptoms recurred when specific dietary proteins were reintroduced during open food challenges. The mechanism of these observations is unknown.

Is neurally mediated hypotension an unrecognised cause of chronic fatigue

Neurally mediated hypotension is now recognised as a common cause of otherwise unexplained recurrent syncope, but has not been reported in association with chronic fatigue. We describe seven consecutive non-syncopal adolescents with chronic post-exertional fatigue, four of whom satisfied strict criteria for chronic fatigue syndrome. Upright tilt-table testing induced significant hypotension in all seven (median systolic blood pressure 65 mm Hg, range 37-75), consistent with the physiology of neurally mediated hypotension. Four had prompt improvement in their chronic fatigue when treated with atenolol or disopyramide. These observations suggest an overlap in the symptoms of chronic fatigue syndrome and neurally mediated hypotension.

Embolotherapy for pelvic congestion syndrome : Long-term results

PURPOSE To evaluate the long-term clinical outcome of transcatheter embolotherapy in women with chronic pelvic pain caused by ovarian and pelvic varices. MATERIALS AND METHODS The study population included consecutive patients referred to a tertiary-care interventional radiology service from 1998 to 2003 because of a high degree of clinical suspicion of pelvic and ovarian varices. Visual analog scales and questionnaires during clinic visits were used to measure pain perception levels. Basal female hormonal levels were obtained and compared. RESULTS Of 131 patients referred (mean age, 34.0 years+/-12.5), percutaneous transfemoral venography confirmed the presence of ovarian varices in 127 (97.0%), all of whom were treated with embolotherapy. Internal iliac embolotherapy was performed in 108 of 127 patients (85.0%). Ninety-seven patients completed long-term clinical follow-up (mean 45 months+/-18). The mean pelvic pain level had improved significantly from 7.6+/-1.8 before embolotherapy to 2.9+/-2.8 after embolotherapy (P<.0001). Significant improvement in each category of specific symptoms was also noted (P<.0001). Overall, 83% of the patients exhibited clinical improvement at long-term follow-up, 13% had no significant change, and 4% exhibited worsened condition. No significant change was noted in hormone levels after embolotherapy. Two successful pregnancies were noted after ovarian and pelvic vein embolotherapy. CONCLUSION Direct venographic evaluation with embolotherapy can achieve significant improvement in pain perception levels in patients with chronic pelvic pain caused by pelvic venous congestion.

Pelvic Congestion Syndrome (Pelvic Venous Incompetence): Impact of Ovarian and Internal Iliac Vein Embolotherapy on Menstrual Cycle and Chronic Pelvic Pain

PURPOSE The purpose of this study was to analyze the impact of transcatheter embolotherapy on pain perception and menstrual cycle in women with chronic pelvic pain caused by the presence of ovarian and pelvic varices (ie, women with pelvic congestion syndrome or pelvic venous incompetence). MATERIALS AND METHODS From July 1998 to August 2000, 56 patients (mean age, 32.3 y) were treated for chronic pelvic pain. Diagnostic venography of the ovarian veins was followed by transcatheter embolotherapy with a sclerosing agent and coils. A second session was completed to embolize the internal iliac veins in 43 of 56 patients. Visual analog scales (VAS) used to measure pain were administered before embolization and at 3-, 6-, and 12-month follow-up. Questionnaires regarding menstrual history were used as part of the postprocedural analysis. RESULTS Percutaneous transcatheter embolotherapy of ovarian and pelvic varices was technically successful in 56 of 56 patients (100%); three patients developed recurrent varices, two of whom were treated with repeat transcatheter embolotherapy. Two patients, early in the experience, had complications in which coils placed in the internal iliac veins embolized to the pulmonary circulation; the coils were snared without clinical sequelae. On the VAS, the mean baseline pain level was 7.8 (range, 3.2-9.8; n = 56); at 3-month follow-up, it was 4.2 (range, 0.0-7.2; n = 56); at 6 months, 3.8 (range, 0.0-6.7; n = 41); and at 12 months, 2.7 (range, 0.0-6.9; n = 32). Differences were significant (P <.001) between baseline pain levels and those at all follow-up intervals (ie, 3, 6, and 12 months). The mean decrease in VAS was 5.1 (65% decrease). The clinical follow-up in this series ranged between 6 and 38 months; the mean was 22.1 months. Regarding the impact of embolization on menstruation, all 24 patients responding to questionnaires indicated no change in menstrual cycle. CONCLUSION For patients with ovarian/internal iliac varices, transcatheter embolotherapy provides a nonsurgical treatment option. There is a significant decrease in pain based on VAS without any notable impact on menstrual cycle.

Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome

OBJECTIVE To report chronic fatigue syndrome (CFS) associated with both Ehlers-Danlos syndrome (EDS) and orthostatic intolerance. STUDY DESIGN Case series of adolescents referred to a tertiary clinic for the evaluation of CFS. All subjects had 2-dimensional echocardiography, tests of orthostatic tolerance, and examinations by both a geneticist and an ophthalmologist. RESULTS Twelve patients (11 female), median age 15.5 years, met diagnostic criteria for CFS and EDS, and all had either postural tachycardia or neurally mediated hypotension in response to orthostatic stress. Six had classical-type EDS and 6 had hypermobile-type EDS. CONCLUSIONS Among patients with CFS and orthostatic intolerance, a subset also has EDS. We propose that the occurrence of these syndromes together can be attributed to the abnormal connective tissue in dependent blood vessels of those with EDS, which permits veins to distend excessively in response to ordinary hydrostatic pressures. This in turn leads to increased venous pooling and its hemodynamic and symptomatic consequences. These observations suggest that a careful search for hypermobility and connective tissue abnormalities should be part of the evaluation of patients with CFS and orthostatic intolerance syndromes.

Nebulized Budesonide for Children with Mild-to-Moderate Croup

BACKGROUND Although recent evidence has strongly supported the use of glucocorticoid therapy in children hospitalized with croup, the benefit of this therapy in children with less severe croup has not been documented. This randomized, double-blind trial compared a nebulized glucocorticoid, budesonide, with placebo in outpatients with mild-to-moderate croup. METHODS Children three months to five years of age were eligible for the study if their croup scores fell in the mild-to-moderate range (scores of 2 to 7 out of a possible 17). The patients were randomly assigned to receive either 2 mg (4 ml) of nebulized budesonide (27 children) or 4 ml of nebulized normal saline (27 children); they were then assessed hourly for up to four hours by investigators who were unaware of the assigned treatments. RESULTS The median croup score at entry into the study was 4 in both groups. At the final study assessment, the median score was significantly lower in the budesonide group than in the placebo group (1 vs. 3, P = 0.005). The patients in the budesonide group were discharged from the emergency department significantly earlier than those in the placebo group (P = 0.002). One week after enrollment, 21 patients assigned to placebo had received dexamethasone, as compared with 15 patients assigned to budesonide (P = 0.10), and 7 patients assigned to placebo had been admitted to the hospital, as compared with 1 patient assigned to budesonide (P = 0.05). CONCLUSIONS We conclude that nebulized budesonide leads to a prompt and important clinical improvement in children with mild-to-moderate croup who come to the emergency department.

Neurally mediated hypotension and chronic fatigue syndrome.

A substantial body of clinical evidence now supports an association between various forms of hypotension and both idiopathic chronic fatigue and the chronic fatigue syndrome (CFS). Patients with CFS have a high prevalence of neurally mediated hypotension, and open treatment of this autonomic dysfunction has been associated with improvements in CFS symptoms. Randomized trials are now in progress to evaluate the efficacy of treatments directed at neurally mediated hypotension in those with CFS patients, and the results of these trials should help guide more basic inquiries into the mechanisms of orthostatic intolerance in affected individuals.

Diagnostic challenges of early Lyme disease: Lessons from a community case series

BackgroundLyme disease, the most common vector-borne infection in North America, is increasingly reported. When the characteristic rash, erythema migrans, is not recognized and treated, delayed manifestations of disseminated infection may occur. The accuracy of diagnosis and treatment of early Lyme disease in the community is unknown.MethodsA retrospective, consecutive case series of 165 patients presenting for possible early Lyme disease between August 1, 2002 and August 1, 2007 to a community-based Lyme referral practice in Maryland. All patients had acute symptoms of less than or equal to 12 weeks duration. Patients were categorized according to the Centers for Disease Control and Prevention criteria and data were collected on presenting history, physical findings, laboratory serology, prior diagnoses and prior treatments.ResultsThe majority (61%) of patients in this case series were diagnosed with early Lyme disease. Of those diagnosed with early Lyme disease, 13% did not present with erythema migrans; of those not presenting with a rash, 54% had been previously misdiagnosed. Among those with a rash, the diagnosis of erythema migrans was initially missed in 23% of patients whose rash was subsequently confirmed. Of all patients previously misdiagnosed, 41% had received initial antibiotics likely to be ineffective against Lyme disease.ConclusionFor community physicians practicing in high-risk geographic areas, the diagnosis of Lyme disease remains a challenge. Failure to recognize erythema migrans or alternatively, viral-like presentations without a rash, can lead to missed or delayed diagnosis of Lyme disease, ineffective antibiotic treatment, and the potential for late manifestations.

Circulating inflammatory cytokine levels in hemolytic uremic syndrome

Abstract Experimental data suggest that the host’s inflammatory response is involved in the pathophysiology of verotoxin-producing Escherichia coli (VTEC)-associated hemolytic uremic syndrome (HUS). We compared the circulating levels of pro- [interleukin (IL)-6, IL-8] and anti-inflammatory [IL-10 and IL-1 receptor antagonist (Ra)] mediators on enrollment among children with HUS due to E. coli O157:H7, according to the severity of renal dysfunction. The latter was evaluated by the occurrence of oligoanuria, the requirement for dialysis, and a glomerular filtration rate (GFR) ≤80 ml/min per 1.73 m2 measured 1 year later. Increased levels of IL-6 (P<0.0001), IL-10 (P<0.0001), and IL-1Ra (P<0.07) were found among patients with HUS compared with normal controls. Children with severe renal dysfunction also had tenfold increased levels of IL-6 and higher concentrations of IL-10 and IL-1Ra. Both the IL-6/IL-10 (4.9±8.3 vs. 0.5±0.4, P=0.01) and the IL-6/IL-1Ra ratios (0.10±0.20 vs. 0.01±0.01, P=0.04) were significantly increased. GFR correlated well with IL-6 levels, IL-6/IL-10 and IL-6/IL-1Ra ratios. Our data demonstrate that the inflammatory response of the host is associated with the severity of renal dysfunction during classic HUS. An imbalance between the pro- and the anti-inflammatory responses may be involved in the pathophysiology of VTEC-associated HUS.

Gastrointestinal symptoms associated with orthostatic intolerance.

Background: The term orthostatic intolerance is used to describe symptoms of hemodynamic instability such as lightheadedness, fatigue, impaired cognition and syncope that develop on assuming an upright posture. Common forms of orthostatic intolerance in childhood include postural tachycardia syndrome and neurally mediated hypotension. Objective: A descriptive report of the clinical characteristics of patients presenting with gastrointestinal symptoms who are ultimately found to have orthostatic intolerance. Methods: A medical record review of all patients referred to the pediatric gastroenterology service at the Johns Hopkins Childrens Center who had an abnormal tilt table test between June 1996 and December 2000. Results: Of 24 eligible subjects aged 9-17 years (mean, 14.3 years), four had postural tachycardia syndrome, eight had both postural tachycardia and neurally mediated hypotension, and 12 had neurally mediated hypotension alone. The most common presenting gastrointestinal symptoms were abdominal pain, nausea and vomiting. Median number of gastrointestinal symptoms per patient was 3 (range, 1-7), and 87% of the patients experienced gastrointestinal symptoms for more than 1 year and 48% experienced gastrointestinal symptoms for more than 3 years. Follow-up information was available on 18 patients. Seventy-eight percent of patients (14 of 18) had complete resolution of symptoms with treatment of orthostatic intolerance. Conclusion: Pediatric patients with chronic upper gastrointestinal symptoms may have underlying orthostatic intolerance. In patients with upper gastrointestinal symptoms and orthostatic intolerance, treatment of orthostatic intolerance may result in resolution of gastrointestinal symptoms.