Publications by authors named "Julie Prendiville"

31 Publications

Recurrent sterile abscesses in a case of X-linked neutropenia.

Pediatr Dermatol 2020 Jul 23;37(4):742-744. Epub 2020 Mar 23.

Division of Allergy & Immunology, University of British Columbia, Vancouver, BC, Canada.

Cutaneous manifestations are common in monogenic immune disorders, including both infectious and non-infectious etiologies. We report follow-up of a case initially published in Pediatric Dermatology in 2001 of a 13-year-old boy with a history of inflammatory skin lesions and neutropenia who developed neutrophilic dermatoses precipitated by G-CSF. Whole exome sequencing performed at 36 years of age revealed a gain-of-function mutation in the WAS gene, leading to a diagnosis of X-linked neutropenia. This case report provides closure on a decades-long diagnostic odyssey and underscores the importance of genetic sequencing in patients who present with unusual dermatologic findings.
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http://dx.doi.org/10.1111/pde.14146DOI Listing
July 2020

Recessive Mutations in AP1B1 Cause Ichthyosis, Deafness, and Photophobia.

Am J Hum Genet 2019 11 17;105(5):1023-1029. Epub 2019 Oct 17.

Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Dermatology, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address:

We describe unrelated individuals with ichthyosis, failure to thrive, thrombocytopenia, photophobia, and progressive hearing loss. Each have bi-allelic mutations in AP1B1, the gene encoding the β subunit of heterotetrameric adaptor protein 1 (AP-1) complexes, which mediate endomembrane polarization, sorting, and transport. In affected keratinocytes the AP-1 β subunit is lost, and the γ subunit is greatly reduced, demonstrating destabilization of the AP-1 complex. Affected cells and tissue contain an abundance of abnormal vesicles and show hyperproliferation, abnormal epidermal differentiation, and derangement of intercellular junction proteins. Transduction of affected cells with wild-type AP1B1 rescues the vesicular phenotype, conclusively establishing that loss of AP1B1 function causes this disorder.
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http://dx.doi.org/10.1016/j.ajhg.2019.09.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849088PMC
November 2019

JAK1 gain-of-function causes an autosomal dominant immune dysregulatory and hypereosinophilic syndrome.

J Allergy Clin Immunol 2017 06 19;139(6):2016-2020.e5. Epub 2017 Jan 19.

Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2016.12.957DOI Listing
June 2017

The importance of considering monogenic causes of autoimmunity: A somatic mutation in KRAS causing pediatric Rosai-Dorfman syndrome and systemic lupus erythematosus.

Clin Immunol 2017 Feb 31;175:143-146. Epub 2016 Dec 31.

Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Objectives: Clinicians need to be aware of the growing list of defined monogenic etiologies of autoimmune diseases. This is particularly relevant when evaluating children, as these rare monogenic forms of autoimmunity tend to present very early in life.

Methods And Results: By harnessing the transformative power of next generation sequencing, we made the unifying diagnosis of RAS-associated autoimmune leukoproliferative disease (RALD), caused by the somatic gain-of-function p.G13C KRAS mutation, in a boy with the seemingly unrelated immune dysregulatory conditions of Rosai-Dorfman and systemic lupus erythematosus (SLE).

Conclusions: This case expands our understanding of the clinical phenotypes associated with the extremely rare condition of RALD, and emphasizes the importance of always considering the possibility of a monogenic cause for autoimmunity, particularly when the disease manifestations begin early in life and do not follow a typical clinical course.
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http://dx.doi.org/10.1016/j.clim.2016.12.006DOI Listing
February 2017

Vascular Anomalies Classification: Recommendations From the International Society for the Study of Vascular Anomalies.

Pediatrics 2015 Jul 8;136(1):e203-14. Epub 2015 Jun 8.

Laboratory of Human Molecular Genetics, Christian de Duve Institute of Cellular Pathology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

Vascular anomalies represent a spectrum of disorders from a simple "birthmark" to life- threatening entities. Incorrect nomenclature and misdiagnoses are commonly experienced by patients with these anomalies. Accurate diagnosis is crucial for appropriate evaluation and management, often requiring multidisciplinary specialists. Classification schemes provide a consistent terminology and serve as a guide for pathologists, clinicians, and researchers. One of the goals of the International Society for the Study of Vascular Anomalies (ISSVA) is to achieve a uniform classification. The last classification (1997) stratified vascular lesions into vascular malformations and proliferative vascular lesions (tumors). However, additional disease entities have since been identified that are complex and less easily classified by generic headings, such as capillary malformation, venous malformation, lymphatic malformation, etc. We hereby present the updated official ISSVA classification of vascular anomalies. The general biological scheme of the classification is retained. The section on tumors has been expanded and lists the main recognized vascular tumors, classified as benign, locally aggressive or borderline, and malignant. A list of well-defined diseases is included under each generic heading in the "Simple Vascular Malformations" section. A short definition is added for eponyms. Two new sections were created: one dealing with the malformations of individually named vessels (previously referred to as "truncular" malformations); the second groups lesions of uncertain or debated nature (tumor versus malformation). The known genetic defects underlying vascular anomalies are included in an appendix. This classification is meant to be a framework, acknowledging that it will require modification as new scientific information becomes available.
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http://dx.doi.org/10.1542/peds.2014-3673DOI Listing
July 2015

Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.

Am J Med Genet A 2015 Feb 16;167A(2):296-312. Epub 2015 Jan 16.

INSERM UMR 1163, Laboratory of Neurogenetics and Neuroinflammation, Paris Descartes - Sorbonne Paris Cité University, Institut Imagine, Hôpital Necker, Paris, France; Manchester Centre for Genomic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.

Aicardi-Goutières syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi-Goutières syndrome-related genes. Our findings also make it clear that a window of therapeutic opportunity exists relevant to the majority of affected patients and indicate that the assessment of type I interferon activity might serve as a useful biomarker in future clinical trials.
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http://dx.doi.org/10.1002/ajmg.a.36887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382202PMC
February 2015

Combined immunodeficiency associated with homozygous MALT1 mutations.

J Allergy Clin Immunol 2014 May 12;133(5):1458-62, 1462.e1-7. Epub 2013 Dec 12.

Department of Pediatrics, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2013.10.045DOI Listing
May 2014

Successful approach to treatment of Helicobacter bilis infection in X-linked agammaglobulinemia.

J Clin Immunol 2012 Dec 28;32(6):1404-8. Epub 2012 Jul 28.

Department of Pediatrics, BC Children's Hospital and Child & Family Research Institute, University of British Columbia, Vancouver, BC, Canada.

Helicobacter bilis, an unusual cause of chronic infections in patients with X-linked agammaglobulinemia (XLA), is notoriously difficult to diagnose and eradicate. Based on the limited number of cases reported worldwide, we highlight the typical features of H. bilis infection in XLA and provide a rational and successful approach to diagnosis and treatment of this challenging infection.
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http://dx.doi.org/10.1007/s10875-012-9750-8DOI Listing
December 2012

Use of propranolol in treating hemangiomas.

Can Fam Physician 2011 Mar;57(3):302-3

Department of Pediatrics, BC Children's Hospital, Vancouver, BC V6H 3V4, Canada.

Question: I see many children with infantile hemangiomas and have read about new therapeutic options such as propranolol. Is this medication effective and safe for treating hemangiomas in children?

Answer: Most infantile hemangiomas resolve spontaneously without any need for therapy. In many case series, propranolol has been shown to be effective and safe in treating hemangiomas that cause complications. Further studies are required to determine the optimal dose and duration of propranolol treatment for problematic hemangiomas.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056677PMC
March 2011

Acute onset of generalized pruritic rash in a toddler. Diagnosis: systemic allergic (contact) dermatitis to nickel from ingestion of metal coins.

Pediatr Dermatol 2011 Jan-Feb;28(1):53-4

Division of Pediatric Dermatology, Columbia's Children's Hospital, Vancouver, BC, Canada.

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http://dx.doi.org/10.1111/j.1525-1470.2010.01367.xDOI Listing
June 2011

Intracerebral large artery disease in Aicardi-Goutières syndrome implicates SAMHD1 in vascular homeostasis.

Dev Med Child Neurol 2010 Aug;52(8):725-32

Department of Paediatric Neurology, Newcastle General Hospital, Newcastle upon Tyne, UK.

Aim: To describe a spectrum of intracerebral large artery disease in Aicardi-Goutières syndrome (AGS) associated with mutations in the AGS5 gene SAMHD1.

Method: We used clinical and radiological description and molecular analysis.

Results: Five individuals (three males, two females) were identified as having biallelic mutations in SAMHD1 and a cerebral arteriopathy in association with peripheral vessel involvement resulting in chilblains and ischaemic ulceration. The cerebral vasculopathy was primarily occlusive in three patients (with terminal carotid occlusion and basal collaterals reminiscent of moyamoya syndrome) and aneurysmal in two. Three of the five patients experienced intracerebral haemorrhage, which was fatal in two individuals. Post-mortem examination of one patient suggested that the arteriopathy was inflammatory in origin.

Interpretation: Mutations in SAMHD1 are associated with a cerebral vasculopathy which is likely to have an inflammatory aetiology. A similar disease has not been observed in patients with mutations in AGS1 to AGS4, suggesting a particular role for SAMHD1 in vascular homeostasis. Our report raises important questions about the management of patients with mutations in SAMHD1.
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http://dx.doi.org/10.1111/j.1469-8749.2010.03727.xDOI Listing
August 2010

Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response.

Nat Genet 2009 Jul 14;41(7):829-32. Epub 2009 Jun 14.

Academic Unit of Medical Genetics, University of Manchester, Manchester, UK.

Aicardi-Goutières syndrome is a mendelian mimic of congenital infection and also shows overlap with systemic lupus erythematosus at both a clinical and biochemical level. The recent identification of mutations in TREX1 and genes encoding the RNASEH2 complex and studies of the function of TREX1 in DNA metabolism have defined a previously unknown mechanism for the initiation of autoimmunity by interferon-stimulatory nucleic acid. Here we describe mutations in SAMHD1 as the cause of AGS at the AGS5 locus and present data to show that SAMHD1 may act as a negative regulator of the cell-intrinsic antiviral response.
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http://dx.doi.org/10.1038/ng.373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154505PMC
July 2009

Cystic bone lesions in a boy with Darier disease: a magnetic resonance imaging assessment.

J Am Acad Dermatol 2009 Jun;60(6):1062-6

Division of Pediatric Dermatology, British Columbia Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada.

We describe asymptomatic bone cysts in the right humerus of a 17-year-old boy with Darier disease. The cysts were found when a radiographic skeletal survey was performed to monitor for adverse effects of oral retinoid therapy. Magnetic resonance imaging was used to confirm that the lesions were cystic and to delineate their extent. The literature was reviewed for previous reports of this association.
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http://dx.doi.org/10.1016/j.jaad.2008.10.049DOI Listing
June 2009

SLC29A3 gene is mutated in pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome and interacts with the insulin signaling pathway.

Hum Mol Genet 2009 Jun 31;18(12):2257-65. Epub 2009 Mar 31.

Department of Haematology and Genetics, South Eastern Area Laboratory Services, Sydney, NSW 2031, Australia.

Pigmented hypertrichotic dermatosis with insulin-dependent diabetes (PHID) syndrome is a recently described autosomal recessive disorder associated with predominantly antibody negative, insulin-dependent diabetes mellitus. In order to identify the genetic basis of PHID and study its relationship with glucose metabolism, we performed homozygosity mapping in five unrelated families followed by candidate gene sequencing. Five loss-of-function mutations were identified in the SLC29A3 gene which encodes a member of a highly conserved protein family that transports nucleosides, nucleobases and nucleoside analogue drugs, hENT3. We show that PHID is allelic with a related syndrome without diabetes mellitus, H syndrome. The interaction of SLC29A3 with insulin signaling pathways was then studied using an established model in Drosophila melanogaster. Ubiquitous knockdown of the Drosophila ortholog of hENT3, dENT1 is lethal under stringent conditions; whereas milder knockdown induced scutellar bristle phenotypes similar to those previously reported in the knockdown of the Drosophila ortholog of the Islet gene. A cellular growth assay showed a reduction of cell size/number which could be rescued or enhanced by manipulation of the Drosophila insulin receptor and its downstream signaling effectors, dPI3K and dAkt. In summary, inactivating mutations in SLC29A3 cause a syndromic form of insulin-dependent diabetes in humans and in Drosophila profoundly affect cell size/number through interactions with the insulin signaling pathway. These data suggest that further investigation of the role of SLC29A3 in glucose metabolism is a priority for diabetes research.
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http://dx.doi.org/10.1093/hmg/ddp161DOI Listing
June 2009

Parkes Weber syndrome, vein of Galen aneurysmal malformation, and other fast-flow vascular anomalies are caused by RASA1 mutations.

Hum Mutat 2008 Jul;29(7):959-65

Laboratory of Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Brussels, Belgium.

Capillary malformation-arteriovenous malformation (CM-AVM) is a newly recognized autosomal dominant disorder, caused by mutations in the RASA1 gene in six families. Here we report 42 novel RASA1 mutations and the associated phenotype in 44 families. The penetrance and de novo occurrence were high. All affected individuals presented multifocal capillary malformations (CMs), which represent the hallmark of the disorder. Importantly, one-third had fast-flow vascular lesions. Among them, we observed severe intracranial AVMs, including vein of Galen aneurysmal malformation, which were symptomatic at birth or during infancy, extracranial AVM of the face and extremities, and Parkes Weber syndrome (PKWS), previously considered sporadic and nongenetic. These fast-flow lesions can be differed from the other two genetic AVMs seen in hereditary hemorrhagic telangiectasia (HHT) and in phosphatase and tensin homolog (PTEN) hamartomatous tumor syndrome. Finally, some CM-AVM patients had neural tumors reminiscent of neurofibromatosis type 1 or 2. This is the first extensive study on the phenotypes associated with RASA1 mutations, and unravels their wide heterogeneity.
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http://dx.doi.org/10.1002/humu.20746DOI Listing
July 2008

A comparison of disease severity among affected male versus female patients with PHACE syndrome.

J Am Acad Dermatol 2008 Jan 29;58(1):81-7. Epub 2007 Oct 29.

Department of Dermatology at Baylor College of Medicine, Houston, Texas, USA.

Background: PHACE syndrome (Online Mendelian Inheritance in Man database No. 606519) refers to the association of large, plaquelike, or segmental hemangiomas of the face, with one or more of the following anomalies: posterior fossa brain malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, eye anomalies, and ventral developmental defects, specifically sternal defects, supraumbilical raphe, or both.

Objective: The underlying pathogenesis of PHACE is unknown. A strong female predominance exists, leading some to suggest the possibility of X-linked dominant inheritance, with lethality in male patients. However, no familial cases have been reported, and disease severity among affected male patients has not been systematically studied.

Methods: We compared the incidence of syndrome-associated anomalies between 17 new and 42 published reports of male patients with PHACE versus 213 published reports of female patients with PHACE.

Results: A statistically significant difference was found only for structural brain anomalies, which were somewhat more common in male patients.

Limitations: This was a retrospective study. Information was limited on some new and many previously reported cases.

Conclusions: Overall, our results show no convincing trend toward greater or lesser disease severity among affected male patients with PHACE.
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http://dx.doi.org/10.1016/j.jaad.2007.09.009DOI Listing
January 2008

Clinical and molecular phenotype of Aicardi-Goutieres syndrome.

Am J Hum Genet 2007 Oct 4;81(4):713-25. Epub 2007 Sep 4.

Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, LS9 7TF, UK.

Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P=.001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified.
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http://dx.doi.org/10.1086/521373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2227922PMC
October 2007

Quiz page. Acute rheumatic fever with concomitant poststreptococcal glomerulonephritis.

Am J Kidney Dis 2007 Jul;50(1):A33-5

Division of Nephrology, Department of Pediatrics, British Columbia Children's Hospital, Vancouver, Canada.

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http://dx.doi.org/10.1053/j.ajkd.2007.04.001DOI Listing
July 2007

Pigmented hypertrichotic dermatosis and insulin dependent diabetes: manifestations of a unique genetic disorder?

Pediatr Dermatol 2007 Mar-Apr;24(2):101-7

Division of Pediatric Dermatology, Department of Pediatrics, British Columbia's Children's Hospital, University of British Columbia Vancouver, Canada.

A novel pigmented dermatosis was observed in four unrelated boys, three of whom had insulin-dependent diabetes. Three patients were the offspring of consanguineous parents. All four boys had pigmented hypertrichotic patches or induration on the upper inner thighs, with variable involvement of the genitalia, trunk, and limbs. Two boys had episcleritis and orbital proptosis with similar facies and musculoskeletal abnormalities including clinodactyly, flat feet, and short stature. One child had paraaortic and inguinal lymphadenopathy and three patients had an enlarged liver and spleen. A large, swollen pancreas was observed on ultrasound imaging in one patient with insulin dependent diabetes who also had echocardiographic evidence of pericardial inflammation. Three boys had elevated laboratory markers of inflammation. Biopsy specimens from the skin and orbit showed a chronic inflammatory cell infiltrate composed of polyclonal lymphocytes, histiocytes, and plasma cells; fibrosis was observed in two patients, one of whom had previously received radiation therapy to the orbit. Two boys responded to treatment with subcutaneous interferon-alpha, combined with a short course of oral prednisone in the child without diabetes. We believe these inflammatory pigmented skin lesions represent a unique dermatosis associated with diabetes mellitus and systemic disease. The pathogenesis is unknown. The presence of consanguinity in three of four families, and similar dysmorphic features in two boys, suggest a genetic disorder, possibly with autosomal recessive inheritance.
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http://dx.doi.org/10.1111/j.1525-1470.2007.00352.xDOI Listing
July 2007

Keratosis pilaris rubra: a common but underrecognized condition.

Arch Dermatol 2006 Dec;142(12):1611-6

Department of Dermatology, University of California, San Francisco 94143-0316, USA.

Background: Keratosis pilaris is a common skin disorder of childhood that often improves with age. Less common variants of keratosis pilaris include keratosis pilaris atrophicans and atrophodermia vermiculata.

Observations: In this case series from dermatology practices in the United States, Canada, Israel, and Australia, the clinical characteristics of 27 patients with keratosis pilaris rubra are described. Marked erythema with follicular prominence was noted in all patients, most commonly affecting the lateral aspects of the cheeks and the proximal arms and legs, with both more marked erythema and widespread extent of disease than in keratosis pilaris. The mean age at onset was 5 years (range, birth to 12 years). Sixty-three percent of patients were male. No patients had atrophy or scarring from their lesions. Various treatments were used, with minimal or no improvement in most cases.

Conclusions: Keratosis pilaris rubra is a variant of keratosis pilaris, with more prominent erythema and with more widespread areas of skin involvement in some cases, but without the atrophy or hyperpigmentation noted in certain keratosis pilaris variants. It seems to be a relatively common but uncommonly reported condition.
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http://dx.doi.org/10.1001/archderm.142.12.1611DOI Listing
December 2006

Treatment of cystic lymphatic vascular malformations with OK-432 sclerotherapy.

Plast Reconstr Surg 2006 Nov;118(6):1441-1446

Vancouver, British Columbia, Canada From the Vascular Anomalies Clinic, British Columbia Children's Hospital; and Division of Plastic Surgery, Department of Surgery; Department of Radiology; Division of Otolaryngology, Department of Surgery; and Division of Dermatology, Department of Pediatrics, University of British Columbia.

Background: Cystic lymphatic vascular malformations are benign lesions that can cause disfigurement and functional impairment. Complete surgical resection is often difficult, and clinical recurrence is common. Sclerotherapy has been used as an alternative to excision. OK-432 is a lyophilized mixture of Streptococcus pyogenes and benzylpenicillin which, when injected into a lesion, has shown significant ability to reduce its size or obliterate it completely.

Methods: The authors report a series of 12 patients treated in this fashion at the Vascular Anomalies Clinic, British Columbia Children's Hospital, between 1999 and 2004. All patients underwent imaging of the lesion: 10 had magnetic resonance imaging, one had a computed tomographic scan, and one had ultrasound examination. Six patients had macrocystic malformations (cysts > or = 2 cm) and six had microcystic or combined lymphaticovenous malformations. Patients were treated with intralesional injection of OK-432. The position of the injection was confirmed by angiography and/or ultrasound in 10 cases. Response to treatment was assessed clinically.

Results: All patients with macrocystic malformations had complete resolution or good response to treatment. None required any additional treatment. In contrast, those with microcystic or combined malformations responded poorly. All of these patients underwent subsequent excision without adverse consequences. The size and location of the lesion did not correlate with response to treatment. Seventy-five percent of patients experienced pyrexia. Local swelling is an expected phenomenon and must be anticipated, particularly for lesions near the airway.

Conclusions: OK-432 is an excellent treatment for patients with macrocystic lymphatic malformations. However, it is ineffective for microcystic lesions.
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http://dx.doi.org/10.1097/01.prs.0000239503.10964.11DOI Listing
November 2006

Old challenges and new directions in pediatric rheumatology.

J Rheumatol 2006 Jan;33(1):173-84

Department of Rheumatology, Division of Pediatrics, B.C. Children's Hospital, University of British Columbia (UBC), Vancouver, BC, Canada.

A symposium was convened April 2, 2005, by the Department of Pediatrics, University of British Columbia, Vancouver, Canada. The event was a tribute to Dr. Ross Petty on his retirement and in recognition of his contributions to the local and international community of pediatric rheumatology. Speakers were past and present fellows, local basic science and adult rheumatology colleagues, and pediatric rheumatologists from the Pacific North West.
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January 2006

Cerebellar and cerebral atrophy in trichothiodystrophy.

Pediatr Radiol 2005 Oct 24;35(10):1019-23. Epub 2005 May 24.

Department of Radiology, British Columbia Children's Hospital, 4500 Oak Street, Vancouver, BC V6H 3N1, Canada.

Trichothiodystrophy is a rare neuroectodermal disorder of autosomal recessive inheritance that is characterized by brittle hair, nail dysplasia, ichthyosis, mental retardation, and gonadal failure. We describe a female patient whose cranial MRI revealed almost total lack of myelination in the supratentorial white matter, which is similar to the previously described cases. In addition, there was progressive cerebellar and cerebral atrophy, which has not been well documented in association with trichothiodystrophy.
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http://dx.doi.org/10.1007/s00247-005-1495-6DOI Listing
October 2005

A pruritic linear urticarial rash, fever, and systemic inflammatory disease in five adolescents: adult-onset still disease or systemic juvenile idiopathic arthritis sine arthritis?

Pediatr Dermatol 2004 Sep-Oct;21(5):580-8

Division of Pediatric Dermatology, Department of Pediatrics, British Columbia's Children's Hospital, Vancouver, British Columbia, Canada.

The characteristic rash of systemic juvenile idiopathic arthritis is a transient erythematous eruption associated with a quotidian spiking fever. Usually asymptomatic, it can be pruritic, with dermatographism at sites of scratching or pressure. An illness similar to this entity in adults is designated adult-onset Still disease. The relationship between the pediatric and adult disease is uncertain and differences in case definition have evolved. Specifically, a sustained arthritis for at least 6 weeks is required for a diagnosis of systemic juvenile idiopathic arthritis, whereas transient arthritis and arthralgia are accepted criteria in adult-onset Still disease. We describe five patients less than 16 years of age who presented with an acute illness characterized by fever and a distinctive skin eruption. Intense pruritus and linear erythematous lesions flared with a spiking fever, usually in the late afternoon and evening. Periorbital edema/erythema and nonlinear urticarial lesions were also seen. Two children had splinter hemorrhages of the nail beds and one girl developed a fixed, scaling, pigmented, linear eruption. Severe malaise, myalgia, arthralgia, and leukocytosis were present in every patient. Other systemic manifestations included sore throat, transient arthritis, abdominal pain, lymphadenopathy, hepatomegaly, splenomegaly, hyperferritinemia, and hepatic dysfunction. No patient had a sustained arthritis. The course of the disease was variable. One patient, diagnosed with macrophage activation syndrome, recovered on oral naproxen. Two patients responded to systemic corticosteroid therapy. One girl developed status epilepticus and died from aspiration and asphyxia. A boy with severe hepatitis developed renal failure and thrombotic thrombocytopenic purpura and was treated with plasmapheresis, dialysis, and systemic corticosteroids; he had recurrent episodes of rash and fever into adult life. These children did not fulfill the case definition of systemic juvenile idiopathic arthritis because they lacked a persistent arthritis. Adolescent and adult patients with the same clinical and laboratory findings are described under the rubric of adult-onset Still disease. Recognition of the distinctive urticarial skin eruption and spiking fever is important in the diagnosis of a disease with severe morbidity and potentially life-threatening complications.
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http://dx.doi.org/10.1111/j.0736-8046.2004.21513.xDOI Listing
January 2005

Detection and genotyping of varicella-zoster virus by TaqMan allelic discrimination real-time PCR.

J Clin Microbiol 2004 Apr;42(4):1409-13

Department of Pathology and Laboratory Medicine, University of British Columbia and Children's & Women's Health Centre of British Columbia, Canada.

A proportion of individuals vaccinated with live attenuated Oka varicella-zoster virus (VZV) vaccine subsequently develop attenuated chicken pox and/or herpes zoster. To determine whether postvaccination varicella infections are caused by vaccine or wild-type virus, a simple method for distinguishing the vaccine strain from wild-type virus is required. We have developed a TaqMan real-time PCR assay to detect and differentiate wild-type virus from Oka vaccine strains of VZV. The assay utilized two fluorogenic, minor groove binding probes targeted to a single nucleotide polymorphism in open reading frame 62 that distinguishes the Oka vaccine from wild-type strains. VZV DNA could be genotyped and quantified within minutes of thermocycling completion due to real-time monitoring of PCR product formation and allelic discrimination analysis. The allelic discrimination assay was performed in parallel with two standard PCR-restriction fragment length polymorphism (RFLP) methods on 136 clinical and laboratory VZV strains from Canada, Australia, and Japan. The TaqMan assay exhibited a genotyping accuracy of 100% and, when compared to both PCR-RFLP methods, was 100 times more sensitive. In addition, the method was technically simpler and more rapid. The TaqMan assay also allows for high-throughput genotyping, making it ideal for epidemiologic study of the live attenuated varicella vaccine.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC387589PMC
http://dx.doi.org/10.1128/jcm.42.4.1409-1413.2004DOI Listing
April 2004

Subcutaneous panniculitic T-cell lymphoma in children: response to combination therapy with cyclosporine and chemotherapy.

J Am Acad Dermatol 2004 Feb;50(2 Suppl):S18-22

Division of Dermatology, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614, USA.

We describe 2 adolescent boys with facial swelling and/or subcutaneous nodules and fever. Extensive evaluation, including several biopsy specimens, led to a diagnosis of subcutaneous panniculitic T-cell lymphoma, an entity rarely seen in children. Both patients were treated with oral cyclosporine in an effort to suppress the cytokine release from T-cells that has been thought to induce the hemophagocytic syndrome. The patients responded dramatically to cyclosporine treatment with defervescence of the fever and reduction in number and size of the subcutaneous nodules. Subsequent therapy with multidrug chemotherapy achieved complete remission in the first patient. This report suggests the value of cyclosporine as a first-line agent coupled with chemotherapy in the treatment of patients with subcutaneous panniculitic T-cell lymphoma. A clinicopathologic review of 8 described pediatric cases of subcutaneous panniculitic T-cell lymphoma is also presented.
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http://dx.doi.org/10.1016/s0190-9622(03)00746-1DOI Listing
February 2004

Central nervous system involvement in neonatal lupus erythematosus.

Pediatr Dermatol 2003 Jan-Feb;20(1):60-7

Division of Pediatric Dermatology, Department of Pediatrics, British Columbia's Children's Hospital, Vancouver, British Columbia, Canada.

Computerized tomography (CT) of the brain was performed in 10 of 11 consecutive infants with neonatal lupus erythematosus (NLE) (five boys and six girls). Ten of the 11 infants had brain neurosonography. Nine of 10 infants had abnormal CT scans. There was diffuse, markedly reduced attenuation of the cerebral white matter in four infants studied in the first week of life, and also in an infant 5 weeks of age. Patchy reduced subcortical white matter attenuation was observed in another 5-week-old infant. Basal ganglia calcifications were present in two infants at 2 months of age, one of whom also had mild ventriculomegaly. A patient with macrocephaly studied at 4 months of age had enlarged ventricles and subarachnoid spaces consistent with benign macrocephaly of infancy. Cerebral ultrasound examination was abnormal in all five infants studied in the first week of life and in one infant at 2 months of age. Findings included subependymal cysts (4), echogenic white matter (3), and echogenic lenticulostriate vessels (3). Apart from one case of macrocephaly, there was no clinical evidence of neurologic disease and the subsequent development of these infants has been normal. Subclinical central nervous system (CNS) disease in NLE is likely to be a transient phenomenon that resolves as maternal antibodies are cleared from the infant's circulation. It is important to be aware of these neuroimaging abnormalities to avoid misdiagnosis of congenital viral infection in a newborn with multisystem NLE. The potential for neurologic sequelae is uncertain.
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http://dx.doi.org/10.1046/j.1525-1470.2003.03014.xDOI Listing
June 2003

Stevens-Johnson syndrome and toxic epidermal necrolysis.

Adv Dermatol 2002 ;18:151-73

Division of Pediatric Dermatology, Department of Pediatrics, University of British Columbia, British Columbia Children's Hospital, Vancouver, Canada.

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February 2003