Kikuchi-Fujimoto Disease With Unusual Cutaneous Findings.

ABSTRACT: We present a case of the rare Kikuchi-Fujimoto disease (KFD) in a 14-year-old patient admitted to UCLA Medical Center with fever, weight loss, and pancytopenia. Physical examination revealed tender subcutaneous nodules and cervical lymphadenopathy. A lymph node biopsy showed findings consistent with KFD. The skin biopsy showed mild superficial dermal edema with neutrophil-predominant inflammation. In addition, rare atypical monocytoid cells were seen. This histologic finding of a Sweet-like morphology has not been reported previously in the literature in association with KFD. The differential diagnosis included Sweet syndrome arising in association with KFD, underlying connective tissue, and an infectious etiology.

Eosinophilic dermatosis of hematologic malignancy effectively controlled with omalizumab maintenance therapy.

Treatment of eosinophilic dermatosis of hematologic malignancy (EDHM) has been challenging with a minimal response to several modalities. Only systemic corticosteroids have consistently proven successful in suppressing the rash; however, the response is often only partial, and symptoms tend to recur as the dosage is tapered. This demonstrates the need for effective maintenance therapy. Herein, we present a case of EDHM that, following a 1 month prednisone taper and brief trial of narrow-band ultraviolet B phototherapy, has remained well-controlled with omalizumab. This suggests that omalizumab may represent an effective therapeutic alternative in EDHM management with low long-term toxicity.

Rare Case Report of Pilomatrical Carcinosarcoma in a Pediatric Patient.

We present a case report of the exceptionally rare pilomatrical carcinosarcoma in an even rarer pediatric age group, a 9-year-old female patient. The tumor showed biphasic pilomatrical carcinoma and malignant sarcomatous transformation. To date, the patient is healing well without signs of recurrence. Although limited clinical follow-up is available due to the recent diagnosis, this case may provide a rare look at the clinical outcome of this very rare tumor.

Success rates in pediatric WPW ablation are improved with 3-dimensional mapping systems compared with fluoroscopy alone: a multicenter study.

INTRODUCTION: Three-dimensional mapping (3-D) systems are frequently used for ablation of supraventricular tachycardia. Prior studies have demonstrated radiation dosage reduction with 3-D, but there are no data on whether 3-D improves the efficacy of ablation of Wolff-Parkinson-White syndrome (WPW). We sought to determine if 3-D improves the success rate for ablation of WPW in children. METHODS: Multicenter retrospective study including patients ≤21 years of age with WPW undergoing ablation from 2008 to 2012. Success rates using the 2 techniques (3-D vs. fluoroscopy alone [FLUORO]) were compared. RESULTS: Six hundred and fifty-one cases were included (58% male, mean age 13 ± 4 years, 366 [56%] 3-D). Baseline characteristics including gender, weight, accessory pathway (AP) location, number of APs, and repeat ablation attempts were similar between the 2 groups (3-D and FLUORO) The 3-D group was slightly younger (12.7 ± 4.0 vs. 13.3 ± 4.0 years; P = 0.04) and less likely to undergo ablation utilizing cryoenergy (38 [10%] vs. 56 [20%]; P < 0.01). The 3-D group had a higher acute success rate of ablation (355 [97%] vs. 260 [91%]; P < 0.01). No differences were seen in recurrence (16 [5%] vs. 26 [9%]; P = 0.09) or complication rates (1 [0.3%] vs. 1 [0.4%]; P = 0.86) between the groups. On multivariable analysis, 3-D was shown to significantly improve success at ablation with an odds ratio of 3.1 (95% CI 1.44-6.72; P < 0.01). CONCLUSIONS: Use of 3-D significantly improved success rates for ablation of WPW in children. The increase in acute success associated with 3-D suggests it is an important adjunct for catheter ablation of WPW in children.

Three-Catheter Technique for Ablation of Left-Sided Accessory Pathways in Wolff-Parkinson-White is Less Expensive and Equally Successful When Compared to a Five-Catheter Technique.

PURPOSE: To compare the efficacy, safety, and cost-effectiveness of a three-catheter approach with a conventional five-catheter approach for the mapping and ablation of supraventricular tachycardia in pediatric patients with Wolff-Parkinson-White Syndrome (WPW) and concealed accessory pathways (APs). METHODS: A retrospective review from 2008 to 2012 of patients less than 21 years with WPW who underwent a three-catheter radiofrequency (RF) ablation of a left-sided AP (ablation, right ventricular [RV] apical, and coronary sinus [CS] decapolar catheters) was performed. The three-catheter group was compared to a control group who underwent a standard five-catheter (ablation, RV apical, CS decapolar, His catheter, and right atrial catheter) ablation for the treatment of left-sided WPW or concealed AP. Demographics, ablation outcomes, and costs were compared between groups. RESULTS: Twenty-eight patients met inclusion criteria with 28 control patients. The groups did not differ in gender, age, weight, or body surface area. Locations of the AP on the mitral annulus were similar between the groups. All patients were ablated via transseptal approach. Note that 28 of 28 in the three-catheter group (100%) and 27 of 28 (96%) controls were acutely successfully ablated (P = 0.31). No complications were encountered. There was no difference in procedural time, time to loss of AP conduction, or number of RF applications. Use of the three-catheter technique resulted in a total savings of $2,465/case, which includes the $680 savings from using fewer catheters as well as the savings from a shortened procedure time. CONCLUSIONS: Ablation in patients with WPW and a left-sided AP can be performed using three catheters with similar efficacy and safety while offering significant cost savings compared to a conventional five-catheter approach.

The prevalence of arrhythmias, predictors for arrhythmias, and safety of exercise stress testing in children.

Exercise testing is commonly performed in children for evaluation of cardiac disease. Few data exist, however, on the prevalence, types of arrhythmias, predictors for arrhythmias, and safety of exercise testing in children. A retrospective review of all patients ≤21 years undergoing exercise testing at our center from 2008 to 2012 was performed. Patients with clinically relevant arrhythmias were compared to those not experiencing a significant arrhythmia. 1,037 tests were performed in 916 patients. The mean age was 14 ± 4 years, 537 (55 %) were male, 281 (27 %) had congenital heart disease, 178 (17 %) had a history of a prior arrhythmia, and 17 (2 %) had a pacemaker or ICD. 291 (28 %) patients had a rhythm disturbance during the procedure. Clinically important arrhythmias were noted in 34 (3 %) patients and included: 19 (1.8 %) increasing ectopy with exercise, 5 (0.5 %) VT, 5 (0.5 %) second degree AV block, 3 (0.3 %) SVT, and 2 (0.2 %) AFIB. On multivariate logistic regression, variables associated with the development of clinically relevant arrhythmias included severe left ventricular (LV) dysfunction on echo (OR 1.99, CI 1.20-3.30) and prior history of a documented arrhythmia (OR 2.94, CI 1.25-6.88). There were no adverse events related to testing with no patient requiring cardioversion, defibrillation, or acute anti-arrhythmic therapy. A total of 28 % of children developed a rhythm disturbance during exercise testing and 3 % were clinically important. Severe LV dysfunction and a history of documented arrhythmia were associated with the development of a clinically important arrhythmia.

Reducing patient radiation exposure during paediatric SVT ablations: use of CARTO® 3 in concert with "ALARA" principles profoundly lowers total dose.

BACKGROUND: "ALARA--As Low As Reasonably Achievable" protocols reduce patient radiation dose. Addition of electroanatomical mapping may further reduce dose. METHODS: From 6/11 to 4/12, a novel ALARA protocol was utilised for all patients undergoing supraventricular tachycardia ablation, including low frame rates (2-3 frames/second), low fluoro dose/frame (6-18 nGy/frame), and other techniques to reduce fluoroscopy (ALARA). From 6/12 to 3/13, use of CARTO® 3 (C3) with "fast anatomical mapping" (ALARA+C3) was added to the ALARA protocol. Intravascular echo was not utilised. Demographics, procedural, and radiation data were analysed and compared between the two protocols. RESULTS: A total of 75 patients were included: 42 ALARA patients, and 33 ALARA+C3 patients. Patient demographics were similar between the two groups. The acute success rate in ALARA was 95%, and 100% in ALARA+C3; no catheterisation-related complications were observed. Procedural time was 125.7 minutes in the ALARA group versus 131.4 in ALARA+C3 (p=0.36). Radiation doses were significantly lower in the ALARA+C3 group with a mean air Kerma in ALARA+C3 of 13.1±28.3 mGy (SD) compared with 93.8±112 mGy in ALARA (p<0.001). Mean dose area product was 92.2±179 uGym2 in ALARA+C3 compared with 584±687 uGym2 in ALARA (p<0.001). Of the 33 subjects (42%) in the ALARA+C3 group, 14 received ⩽1 mGy exposure. The ALARA+C3 dosages are the lowest reported for a combined electroanatomical-fluoroscopy technique. CONCLUSIONS: Addition of CARTO® 3 to ALARA protocols markedly reduced radiation exposure to young people undergoing supraventricular tachycardia ablation while allowing for equivalent procedural efficacy and safety.

Eruptive Melanocytic Nevi in the Setting of Encorafenib, Cetuximab, and Binimetinib Combination Therapy: A Case Report.

Introduction: The development of new and changing melanocytic lesions has been increasingly reported as an adverse dermatologic toxicity of BRAF inhibitor therapy. Melanocytic lesions and melanomas induced by BRAF inhibitor therapy that lack BRAF V600E expression have been less commonly described. One mechanism that has been proposed for the development of BRAF inhibitor-induced melanocytic lesions, including those lacking BRAF V600E expression, is the paradoxical activation of the MAPK signaling pathway in BRAF wild-type (BRAFWT) cells. Case Presentation: Herein, we report a rare case of a 39-year-old woman who developed numerous BRAF V600E-negative eruptive melanocytic nevi following encorafenib, cetuximab, and binimetinib combination therapy, the current standard of care for the treatment of BRAF-mutant metastatic colorectal cancer. Conclusion: Patients treated with BRAF inhibitors, with or without related combination therapies, who develop BRAFWT melanocytic lesions are at risk for developing both dysplastic nevi and melanoma, thereby warranting baseline dermatoscopic evaluation prior to the initiation of therapy as well as regular follow-up during and after treatment.

Lone atrial fibrillation in the young - perhaps not so "lone"?

OBJECTIVE: To determine if pediatric patients with a history of lone atrial fibrillation (AF) have other forms of supraventricular tachycardia (SVT) that may potentially trigger AF. STUDY DESIGN: A multicenter review of patients with lone AF who underwent electrophysiology (EP) study from 2006-2011 was performed. INCLUSION CRITERIA: age ≤21 years, normal ventricular function, structurally normal heart, history of AF, and EP study and/or ablation performed. EXCLUSION CRITERIA: congenital heart disease or cardiomyopathy. Patient demographics, findings at EP study and follow-up data were recorded. RESULTS: Eighteen patients met inclusion criteria. The mean age was 17.9 ± 2.2 years, weight was 82 ± 21 kg, body mass index was 27 ± 6, and 15 (83%) were males. Eleven (61%) were overweight or obese. Seven (39%) had inducible SVT during EP study: 5 atrioventricular nodal re-entry tachycardia (71%) and 2 concealed accessory pathways with inducible atrioventricular re-entry tachycardia (29%). All 7 patients with inducible SVT underwent radiofrequency ablation. There were no complications during EP study and/or ablation for all 18 patients. The mean follow-up was 1.7 ± 1.5 years and there were no recurrences in the 7 patients who underwent ablation. There were 2 recurrences of AF in patients with no other form of SVT during EP study. CONCLUSIONS: Inducible SVT was found in 39% of pediatric patients undergoing EP study for lone AF. EP study should be considered for pediatric patients presenting with lone AF.

Reducing patient radiation dosage during pediatric SVT ablations using an "ALARA" radiation reduction protocol in the modern fluoroscopic era.

BACKGROUND: Ablation for supraventricular tachycardia (SVT) relies upon fluoroscopy (fluoro), which exposes the patient and staff to ionizing radiation. The objective of this work was to present a new "ALARA--As Low As Reasonably Achievable" protocol with alterations to fluoroscopic x-ray parameters to reduce dose without an electroanatomical (EAM) approach. METHODS: All patients <21 years of age undergoing ablation of SVT at our institution from June 2011 to April 2012 were included. EAM was not utilized in any case. An ALARA protocol of low frame rates (2 or 3 fps), low fluoro dose/frame (10-18 nGy/frame), and other techniques aimed at reducing use of fluoroscopy were employed. Demographics, procedural, and radiation data were analyzed. RESULTS: Forty-two patients underwent ablation and were studied. Median age was 14.1 years (range 4.8-21.1 years), weight was 51 kg (range 18.2-75 kg), and body surface area was 1.51 m(2) (range 0.72- 1.94 m(2)). Seventeen (41%) had Wolff-Parkinson-White syndrome, 14 (33%) atrioventricular nodal reentrant tachycardia, and 11 (26%) concealed pathways. Median procedural time was 114 minutes (57-246 minutes). Median dose area product (DAP) for posterioanterior and lateral fluoroscopy was 343.2 uGym(2) (range 38.2-3,172 uGym(2)); the median air Kerma product (K) was 45.4 mGy (range 6.7-567.5 mGy). DAP and K are lower than prior data from EAM and fluoroscopy techniques. The acute success rate was 95%; no procedural complications. CONCLUSIONS: An ALARA protocol for ablation of SVT reduced radiation to below levels previously reported for combined EAM/fluoro approaches. Success rates were excellent with no complications and without the costs of EAM.

Clinical and electrophysiologic characteristics of antidromic tachycardia in children with Wolff-Parkinson-White syndrome.

BACKGROUND: Antidromic reciprocating tachycardia (ART) is a rare form of wide complex tachycardia in children with Wolff-Parkinson-White syndrome (WPW). The incidence and electrophysiologic characteristics of ART in children with WPW have not been well described. METHODS: A multicenter retrospective analysis of all patients with WPW undergoing electrophysiology (EP) study from 1990 to 2009 was performed. Patients with clinical or inducible ART were included. RESULTS: A total of 1,147 patients with WPW underwent EP study and 30 patients had ART (2.6%) and were the subject of this analysis. The mean age was 16±3 years, weight was 65±16 kg, and tachycardia cycle length was 305±55 ms. There were two patients (7%) with congenital heart disease (both with Ebstein's anomaly). Four patients (13%) had more than one accessory pathway (AP). The location of the AP was left sided in 53% of patients and right sided in 47%, with septal location and left lateral pathways most commonly involved. AP conduction was found to be high risk in 17 patients (57%). Ablation was not attempted in two patients (7%) due to proximity to the HIS and risk of heart block. Ablation was acutely successful in 93% of the patients in whom it was attempted. CONCLUSIONS: ART is a rare finding in children undergoing EP study. Over half of the patients with ART were found to be high risk and multiple AP were uncommon. Unlike the adult population, ART occurred commonly with septal APs.

Condyloma latum of the plantar foot: Case report of an unusual manifestation of secondary syphilis.

Condyloma lata, a cutaneous manifestation of secondary syphilis, typically presents as verrucous papules or plaques in the anogenital area. Here, we present a case of secondary syphilis presenting in a 38-year-old man as condyloma latum of the plantar foot in the absence of other cutaneous findings of secondary syphilis. The plantar foot is an unusual location for condyloma lata which has not previously been reported in the medical literature. Histopathology was essential to diagnosis in this case and demonstrated verrucous epidermal hyperplasia with a plasma cell-rich infiltrate in the dermis and innumerable spirochetes in the epidermis. The patient was successfully treated with intramuscular penicillin benzathine G. Given the recent rise in the incidence of primary and secondary syphilis, it is essential for clinicians to be aware of atypical presentations of secondary syphilis to avoid delays in treatment and decrease the risk of transmission to sexual partners.

Loss of ventricular preexcitation during noninvasive testing does not exclude high-risk accessory pathways: A multicenter study of WPW in children.

BACKGROUND: Abrupt loss of ventricular preexcitation on noninvasive evaluation, or nonpersistent preexcitation, in Wolff-Parkinson-White syndrome (WPW) is thought to indicate a low risk of life-threatening events. OBJECTIVE: The purpose of this study was to compare accessory pathway (AP) characteristics and occurrences of sudden cardiac arrest (SCA) and rapidly conducted preexcited atrial fibrillation (RC-AF) in patients with nonpersistent and persistent preexcitation. METHODS: Patients 21 years or younger with WPW and invasive electrophysiology study (EPS) data, SCA, or RC-AF were identified from multicenter databases. Nonpersistent preexcitation was defined as absence/sudden loss of preexcitation on electrocardiogram, Holter monitoring, or exercise stress test. RC-AF was defined as clinical preexcited atrial fibrillation with shortest preexcited R-R interval (SPERRI) ≤ 250 ms. AP effective refractory period (APERP), SPERRI at EPS , and shortest preexcited paced cycle length (SPPCL) were collected. High-risk APs were defined as APERP, SPERRI, or SPPCL ≤ 250 ms. RESULTS: Of 1589 patients, 244 (15%) had nonpersistent preexcitation and 1345 (85%) had persistent preexcitation. There were no differences in sex (58% vs 60% male; P=.49) or age (13.3±3.6 years vs 13.1±3.9 years; P=.43) between groups. Although APERP (344±76 ms vs 312±61 ms; P<.001) and SPPCL (394±123 ms vs 317±82 ms; P<.001) were longer in nonpersistent vs persistent preexcitation, there was no difference in SPERRI at EPS (331±71 ms vs 316±73 ms; P=.15). Nonpersistent preexcitation was associated with fewer high-risk APs (13% vs 23%; P<.001) than persistent preexcitation. Of 61 patients with SCA or RC-AF, 6 (10%) had nonpersistent preexcitation (3 SCA, 3 RC-AF). CONCLUSION: Nonpersistent preexcitation was associated with fewer high-risk APs, though it did not exclude the risk of SCA or RC-AF in children with WPW.

Validation of a novel automated signal analysis tool for ablation of Wolff-Parkinson-White Syndrome.

BACKGROUND: In previous pilot work we demonstrated that a novel automated signal analysis tool could accurately identify successful ablation sites during Wolff-Parkinson-White (WPW) ablation at a single center. OBJECTIVE: We sought to validate and refine this signal analysis tool in a larger multi-center cohort of children with WPW. METHODS: A retrospective review was performed of signal data from children with WPW who underwent ablation at two pediatric arrhythmia centers from 2008-2015. All patients with WPW ≤ 21 years who underwent invasive electrophysiology study and ablation with ablation signals available for review were included. Signals were excluded if temperature or power delivery was inadequate or lesion time was < 5 seconds. Ablation lesions were reviewed for each patient. Signals were classified as successful if there was loss of antegrade and retrograde accessory pathway (AP) conduction or unsuccessful if ablation did not eliminate AP conduction. Custom signal analysis software analyzed intracardiac electrograms for amplitudes, high and low frequency components, integrated area, and signal timing components to create a signal score. We validated the previously published signal score threshold 3.1 in this larger, more diverse cohort and explored additional scoring options. Logistic regression with lasso regularization using Youden's index criterion and a cost-benefit criterion to identify thresholds was considered as a refinement to this score. RESULTS: 347 signals (141 successful, 206 unsuccessful) in 144 pts were analyzed [mean age 13.2 ± 3.9 years, 96 (67%) male, 66 (45%) left sided APs]. The software correctly identified the signals as successful or unsuccessful in 276/347 (80%) at a threshold of 3.1. The performance of other thresholds did not significantly improve the predictive ability. A signal score threshold of 3.1 provided the following diagnostic accuracy for distinguishing a successful from unsuccessful signal: sensitivity 83%, specificity 77%, PPV 71%, NPV 87%. CONCLUSIONS: An automated signal analysis software tool reliably distinguished successful versus unsuccessful ablation electrograms in children with WPW when validated in a large, diverse cohort. Refining the tools using an alternative threshold and statistical method did not improve the original signal score at a threshold of 3.1. This software was effective across two centers and multiple operators and may be an effective tool for ablation of WPW.

Impact of intermittent hypoxia on long-term facilitation of minute ventilation and heart rate variability in men and women: do sex differences exist?

Following exposure to intermittent hypoxia, respiratory motor activity and sympathetic nervous system activity may persist above baseline levels for over an hour. The present investigation was designed to determine whether sustained increases in minute ventilation and sympathovagal (S/V) balance, in addition to sustained depression of parasympathetic nervous system activity (PNSA), were greater in men compared with women following exposure to intermittent hypoxia. Fifteen healthy men and women matched for age, race, and body mass index were exposed to eight 4-min episodes of hypoxia during sustained hypercapnia followed by a 15-min end-recovery period. The magnitude of the increase in minute ventilation during the end-recovery period, compared with baseline, was similar in men and women (men, 1.52 +/- 0.03; women, 1.57 +/- 0.02 fraction of baseline; P < 0.0001). In contrast, depression of PNSA and increases in S/V balance were evident during the end-recovery period, compared with baseline, in men (PNSA, 0.66 +/- 0.06 fraction of baseline, P < 0.0001; S/V balance, 2.8 +/- 0.7 fraction of baseline, P < 0.03) but not in women (PNSA, 1.27 +/- 0.19 fraction of baseline, P = 0.3; S/V balance, 1.8 +/- 0.6 fraction of baseline, P = 0.2). We conclude that a sustained increase in minute ventilation, which is indicative of long-term facilitation, is evident in both men and women following exposure to intermittent hypoxia and that this response is independent of sex. In contrast, sustained alterations in autonomic nervous system activity were evident in men but not in women.

Sympathetic drive is modulated by central chemoreceptor activation.

To determine the effects of central chemoreceptor stimulation upon sympathetic modulation while minimizing baroreceptor influences, we performed a single-blind, counter-balanced, placebo-controlled trial of a modified hypercapnic/hyperoxic rebreathe protocol stimulus to activate the central chemoreflex. Muscle sympathetic nerve activity (MSNA), heart rate, blood pressure, and ventilation were recorded dynamically as subjects transitioned from a hypocapnia to hypercapnia state. The stages of data recording were defined as hyperventilation (HyV), pre-threshold (PreT) and post-threshold (PostT), with threshold being defined as the point of non-linear deviation in ventilation. The changes in MSNA (-4.2+/-52.4 arbitrary units (AU) vs. 245.0+/-84.0AU) and burst count (-0.1+/-0.7 bursts/segment vs. 2.5+/-1.7 bursts/segment) were significantly different between control and rebreathe for the HyV to PreT step. There was also a significant difference for PreT to PostT for total MSNA (3.9+/-65.4AU vs. 183.7+/-104.2AU). In a hypercapnic/hyperoxic state, the central chemoreceptors modulate sympathetic activity below the chemoreflex threshold independently of the baroreceptors, possibly contributing to basal autonomic/sympathetic tone. Central chemoreceptors also appear to play a significant role in sympathetic modulation after the threshold.

Pulse Granulomas of the Gastrointestinal Tract and Gallbladder: Report of Five Cases.

Hyaline rings with admixed multinucleated giant cells characterize pulse granulomas; the term pulse refers to edible seeds of legume vegetables. The etiology has been controversial, with theories including vascular degenerative changes or a reaction to vegetable material; ultrastructural studies and experimentally induced lesions in animals favor the latter. This lesion is typically seen in the oral cavity, with only rare reports in the gastrointestinal tract and gallbladder. We herein describe five cases of pulse granulomas identified in these sites. All cases contained foreign-body giant cells and vegetable debris within or near hyaline rings. Pulse granulomas may form mass lesions but are usually an incidental finding on microscopic examination. In incidentally detected cases, recognition of pulse granulomas can suggest a mural abscess, fistula, or perforation of the gut, findings which may not be grossly apparent. The presence of vegetable material in all five cases further supports an exogenous pathogenesis.