Search PubMed⌕ Search

Biomedical subjects

I J Frieden

Publications and source records attributed to I J Frieden.

At least 19 recordsLinked to original sources
PubMed2006

A prospective study of PHACE syndrome in infantile hemangiomas: demographic features, clinical findings, and complications.

PHACE (OMIM no. 606519) is a neurocutaneous syndrome that refers to the association of large, plaque-like, "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 and/or supraumbilical raphe. The etiology and pathogenesis of PHACE is unknown, and potential risk factors for the syndrome have not been systematically studied. The purpose of this study was thus to determine (1) the incidence of PHACE and associated anomalies among a large cohort of hemangioma patients, (2) whether certain demographic, prenatal or perinatal risk factors predispose infants to this syndrome, and (3) whether the cutaneous distribution of the hemangioma can be correlated to the types of anomalies present. We undertook a prospective, cohort study of 1,096 children with hemangiomas, 25 of whom met criteria for PHACE. These 25 patients represented 20% of infants with segmental facial hemangiomas. Compared to previous reports, our PHACE patients had a higher incidence of cerebrovascular and cardiovascular anomalies. Two developed acute arterial ischemic stroke during infancy, while two with cardiovascular anomalies showed documented evidence of normalization, suggesting that both progressive and regressive vascular phenomena may occur in this syndrome. Correlation to the anatomic location of the hemangioma appears to be helpful in determining which structural abnormalities might be present. A comparison of demographic and perinatal data between our PHACE cases and the hemangioma cohort overall showed no major differences, except a trend for PHACE infants to be of slighter higher gestational age and born to slightly older mothers. Eighty-eight percent were female, a finding which has been noted in multiple other reports. Further research is needed to determine possible etiologies, optimal evaluation, and outcomes.

Abnormalities, Multiple↗
PubMed2005

Corticosteroid treatment of periorbital haemangioma of infancy: a review of the evidence.

AIM: To systematically review the literature for corticosteroid treatment of periorbital haemangioma of infancy (HOI) and determine the relative efficacy and safety of oral, topical and intralesional corticosteroids. METHODS: PubMed and the Cochrane Library were queried using keywords, and further articles were obtained by reviewing bibliographies. Inclusion and exclusion criteria were applied to create a subset of literature for analysis. RESULTS: Systematic review revealed 81 original reports of periorbital HOI cases treated with steroids. Most studies and case series failed to document refractive error or visual acuity before and after treatment. Of cases meeting inclusion criteria, five patients received topical steroids and 25 patients received intralesional steroids. Patients receiving intralesional injections tended to demonstrate reduced astigmatism at follow up after treatment (21 of 28). The lack of studies with relevant objective ophthalmological end points prevented statistical meta-analysis. CONCLUSION: Intralesional injections may reduce refractive error, while the efficacy of topical steroids is unclear. Studies measuring objective ophthalmic data before and after treatment are sparse, and more studies are needed to determine the relative efficacy of different steroids. There are insufficient data to estimate the incidence of steroid side effects in patients treated with steroids for periorbital HOI or complications of intralesional injections in particular.

Administration, Oral↗
PubMed2001

Giant congenital melanocytic nevi: the significance of neurocutaneous melanosis in neurologically asymptomatic children.

Patients with a giant congenital melanocytic nevus can develop melanotic tumors characterized by central nervous system involvement, termed leptomeningeal melanocytosis or neurocutaneous melanosis. Although symptomatic neurocutaneous melanosis is rare, we previously reported distinct magnetic resonance (MR) findings of T1 shortening, strongly suggestive of neurocutaneous melanosis, in 30 percent (6 of 20) of children with giant congenital melanocytic nevi who presented initially without neurological symptoms. The purpose of this study was to determine the incidence of neurocutaneous melanosis in high-risk patients and its long-term clinical significance. Magnetic resonance imaging was recommended for all 46 patients with "at-risk" giant congenital melanocytic nevi involving the skin overlying the dorsal spine or scalp. The clinical histories and follow-up of these patients were evaluated by retrospective chart review. Forty-two underwent MR imaging of the brain and 11 underwent additional MR scanning of the spinal cord. Abnormalities were identified in 14 of 43 MR studies, and 23 percent (n = 10) had T1 shortening indicative of melanotic rests within the brain or meninges. None had associated masses or leptomeningeal thickening. The most common areas of involvement in these 10 included the amygdala (n = 8), cerebellum (n = 5), and pons (n = 3). In the group of 11 patients with spinal MR scans, a tethered spinal cord was demonstrated in one. Additional abnormalities were detected by MR scanning, including a middle cranial fossa arachnoid cyst, a Chiari type I malformation, and a crescentic enhancement that subsequently resolved. Clinical follow-up averaging 5 years (range, 2 to 8 years) revealed that only one of the 46 patients evaluated developed neurological symptoms, manifested as developmental delay, hypotonia, and questionable seizures but no other signs of neurocutaneous melanosis. No patient has developed a cutaneous or central nervous system melanoma. Magnetic resonance findings of neurocutaneous melanosis are relatively common, even in asymptomatic children with giant congenital melanocytic nevi. Although these findings suggest an increased lifetime risk of central nervous system melanoma, they do not signify the eventual development of symptomatic neurocutaneous melanosis during childhood.

Brain↗
PubMed2001

Rudimentary meningocele: remnant of a neural tube defect?

BACKGROUND: Rudimentary meningocele, a malformation in which meningothelial elements are present in the skin and subcutaneous tissue, has been described in the past under a variety of different terms and has also been referred to as cutaneous meningioma. There has been debate as to whether rudimentary meningocele is an atretic form of meningocele or results from growth of meningeal cells displaced along cutaneous nerves OBJECTIVE: We reviewed the clinical, histological, and immunohistochemical characteristics of rudimentary meningocele in an attempt to assess the most likely pathologic mechanism for it. DESIGN: Retrospective study. SETTING: University hospitals. PATIENTS: Thirteen children with rudimentary meningocele. MAIN OUTCOME MEASURES: Medical records were reviewed and histopathologic examination as well as immunohistochemistry studies were performed for each case. A panel of immunoperoxidase reagents (EMA, CD31, CD34, CD57, S-100, and CAM 5.2) was used to assess lineage and to confirm the meningothelial nature of these lesions. RESULTS: Recent evidence indicating a multisite closure of the neural tube in humans suggests that classic meningocele and rudimentary meningocele are on a continuous spectrum. CONCLUSION: Rudimentary meningocele seems to be a remnant of a neural tube defect in which abnormal attachment of the developing neural tube to skin (comparable to that in classic meningocele) could explain the presence of ectopic meningeal tissue. In the majority of cases, no underlying bony defect or communication to the meninges could be detected. However, in light of the probable pathogenesis, imaging studies to exclude any communication to the central nervous system should precede any invasive evaluation or intervention.

Child↗
PubMed2001

Congenital nonprogressive hemangioma: a distinct clinicopathologic entity unlike infantile hemangioma.

BACKGROUND: Infantile hemangiomas are common tumors, distinctive for their perinatal presentation, rapid growth during the first year of life, and subsequent involution-and for their expression of a unique immunophenotype shared by placental microvessels. Occasional "hemangiomas" differ from the classic form in presenting fully formed at birth, then following a static or rapidly involuting course. These congenitally fully developed lesions have generally been assumed to be clinical variants of more typical, postnatally developing hemangiomas. This assumption has not been tested by rigorous histologic and immunophenotypic comparisons. OBJECTIVE: To compare the histologic and immunohistochemical features of congenital nonprogressive hemangiomas with those of typical, postnatally proliferating, hemangiomas. DESIGN: All cellular vascular tumors resected from infants younger than 4 months at Arkansas Children's Hospital, Little Rock, over the past 20 years (43 lesions from 36 patients) were first characterized histologically and immunohistochemically, then clinically by chart review. SETTING: A university-affiliated pediatric hospital. MAIN OUTCOME MEASURES: Histologic appearance, immunoreactivity for the infantile hemangioma-associated antigens GLUT1 and LeY, and clinical behavior. RESULTS: Congenital nonprogressive hemangiomas differed from postnatally proliferating infantile hemangiomas in histologic appearance and immunohistochemical profile. Distinguishing pathologic features of these tumors were lobules of capillaries set within densely fibrotic stroma containing hemosiderin deposits; focal lobular thrombosis and sclerosis; frequent association with multiple thin-walled vessels; absence of "intermingling" of the neovasculature with normal tissue elements; and lack of immunoreactivity for GLUT1 and LeY. CONCLUSION: Congenital nonprogressive hemangiomas are histologically and immunophenotypically distinct from classically presenting hemangiomas of infancy, unlikely to be related to the latter in pathogenesis.

Female↗
PubMed2001

Oral corticosteroid use is effective for cutaneous hemangiomas: an evidence-based evaluation.

OBJECTIVES: To determine the efficacy of systemic corticosteroid therapy in treating enlarging, problematic cutaneous hemangiomas and to assess the relationship of dose to response and adverse effects. DESIGN: A quantitative systematic literature review was performed and inclusion and exclusion criteria were applied. SETTING: Patients were treated in primary care, referral centers, and institutional practices. Most patients were ambulatory, although some required hospitalization. PATIENTS: Inclusion criteria were original case series with a minimum of 5 patients with enlarging, problematic cutaneous hemangiomas treated with systemic corticosteroids. Exclusion criteria were being older than 2 years, receiving simultaneous other treatments, being lost to follow-up, or having insufficient information. Twenty-four original case series met inclusion criteria; 10 case series remained (184 patients) after exclusion criteria were applied. INTERVENTION: Patients were given a mean prednisone equivalent daily dose of 2.9 mg/kg (95% confidence interval [CI], 2.7-3.1 mg/kg) for a mean of 1.8 months (95% CI, 1.5-2.2 months). MAIN OUTCOME MEASURES: Response and rebound rates and dose-response and adverse effects-response relationships in responders vs nonresponders. RESULTS: Response was 84% (95% CI, 78%-89%; range, 60%-100%) and rebound was 36% (95% CI, 29%-44%; range, 0%-65%). A significant difference was found between the mean dose administered to responders vs nonresponders (P<.001). No significant difference was observed as to the occurrence of adverse effects (P =.3). CONCLUSION: Systemic corticosteroid treatment seems to be effective for problematic cutaneous hemangiomas of infancy.

Adrenal Cortex Hormones↗
PubMed2001

Do hair care practices affect the acquisition of tinea capitis? A case-control study.

OBJECTIVE: To determine the influences of hair-grooming practices and environmental factors as risk factors for the acquisition of tinea capitis (TC) in children. DESIGN: Case-control study comparing children with culture-proved TC with age-, sex-, and race-matched control subjects without scalp disease. SETTING: A multicenter study involving 3 urban referral centers in the United States. PARTICIPANTS: A convenience sample of 66 patients aged 12 years and younger presenting to pediatric dermatology clinics with clinical evidence of TC were enrolled as cases. Matched control subjects (n = 68), without known scalp disease, were enrolled from the outpatient pediatric clinics at the same institutions. RESULTS: Significant associations with TC in the conditional logistic regression model were a prior history of TC (odds ratio, 3.11; 95% confidence interval, 1.02-9.43; P =.04) and exposure to TC (odds ratio, 16.32; 95% confidence interval, 3.55-75.16; P =.001). The use of a hair conditioner was statistically significant in the univariable model but not in the multivariable model (odds ratio, 0.46; 95% confidence interval, 0.20-1.08; P =.07). Hairstyling, frequency of washing, use of oils or grease, and other hair care practices were not shown to be associated with the presence of TC. CONCLUSIONS: Hair-grooming practices do not appear to play a major role in the acquisition of TC. Hair conditioners may be protective in children at risk for TC, but further studies are needed to confirm this finding.

Case-Control Studies↗
PubMed2001

Cutaneous manifestations of maternal engraftment in patients with severe combined immunodeficiency: a clinicopathologic study.

SCID is a heterogeneous group of disorders characterized by defective T cell and B cell function. Eczematous and morbilliform eruptions are common, and graft-versus-host disease (GVHD) due to maternal engraftment has been documented. We sought to better characterize SCID-related cutaneous disease observed prior to BMT and to compare the eruption to conventional GVHD. Medical records of 51 patients with SCID treated between 1982 and 1999 were reviewed. Ten of 51 (20%) had rash and evidence of maternal engraftment prior to BMT (study group). Eleven of 51 (22%) had no rash or evidence of engraftment pre-BMT but developed GVHD following transplant (control group). Skin biopsies were available for review for 8/10 of the study group and for 8/11 of the control group. Cutaneous findings consisted of a scaling, erythematous maculopapular eruption spread widely over the trunk and extremities, with near-erythroderma in some patients. Microscopically, biopsies from the study group differed significantly from controls. Key differences included parakeratosis (P < or = 0.01), psoriasiform hyperplasia (P < or = 0.04) and spongiosis (P < or = 0.04). The dermatopathologic findings of transplacental GVHD differ from the pattern of post-transplant GVHD. A 'psoriasiform-lichenoid-spongiotic' pattern with necrotic keratinocytes should trigger consideration of SCID and maternal engraftment in the dermatopathologic evaluation of eruptions of infancy.

Bone Marrow Transplantation↗
PubMed2001

Ulcerated hemangiomas: clinical characteristics and response to therapy.

BACKGROUND: Hemangiomas represent the most common benign tumor of infancy, with ulceration its most frequent complication. OBJECTIVE: Our purpose was to review our experience with this challenging problem by evaluating the clinical features, management, and therapeutic responses of ulcerated hemangiomas. METHODS: A retrospective analysis of ulcerated hemangiomas at the University of California, San Francisco outpatient pediatric dermatology clinics and Oakland Children's Hospital from 1987 to 1997 was performed. RESULTS: The medical records of 60 patients were examined. Forty-nine female and 11 male patients were seen with a female/male ratio of 4.5:1. The majority of ulcerated hemangiomas were of the plaque type (n = 50; 83%) and relatively large; 47 (78%) were larger than 6 cm(2). The perineum was the single most frequently involved site, affected in 20 cases (33%). Topical antibiotics, barrier creams, and bio-occlusive dressings were used in most cases. Systemic antibiotics were used in 26 cases (43%) for overt or presumed infection. Systemic corticosteroids were used in 21 children (37%), 5 of whom did not show a response. Intralesional triamcinolone was used in 7 cases (12%), with 4 showing definite improvement. The flashlamp pulsed-dye laser was the modality used in 22 children (37%), 11 (50%) of whom showed definite improvement, 4 (18%) who showed no significant response, and 1 (5%) who showed definite worsening. Interferon alfa-2a was required in 5 patients (8%), all of whom showed improvement without appreciable neurologic side effects. Immediate surgical excision was required in only 2 cases (3%). Pain control with oral acetaminophen, acetaminophen with codeine, and topical 2.5% lidocaine ointment was effective in managing the pain of lip and perineal hemangiomas, with no side effects noted. CONCLUSION: No one uniformly effective treatment modality was found, and frequently several were used concurrently. The decision to use specific therapies was dependent on the age of the patient, as well as the location, size, and stage of growth or involution of the hemangioma. Our approach to management included 4 major areas: local wound care, management of infection, specific therapeutic modalities (systemic and intralesional corticosteroids, flashlamp pulsed-dye laser, and interferon alfa-2a), and pain management.

Adrenal Cortex Hormones↗
PubMed2001

The many faces of PHACE syndrome.

OBJECTIVES: PHACE is an acronym coined to describe a neurocutaneous syndrome encompassing the following features: posterior fossa brain malformations, large facial hemangiomas, arterial anomalies, cardiac anomalies and aortic coarctation, and eye abnormalities. We evaluated the spectrum of disease and significance of potential underlying brain anomalies among affected children. STUDY DESIGN: The records of 14 patients with PHACE syndrome, evaluated between 1995 and 2000, were retrospectively reviewed. A literature review revealed 116 additional cases. RESULTS: PHACE syndrome represents a spectrum of anomalies, because most affected children have only one extracutaneous manifestation. The syndrome is associated with a high incidence of arterial and structural central nervous system anomalies with secondary neurologic sequelae. The potential for progressive neurovascular disease also exists among those patients with anomalous vasculature. CONCLUSION: PHACE syndrome should be considered in any infant presenting with a large, segmental, plaque-type facial hemangioma. Children at risk should receive careful ophthalmologic, cardiac, and neurologic assessment.

Abnormalities, Multiple↗
PubMed2001

Kwashiorkor in the United States: fad diets, perceived and true milk allergy, and nutritional ignorance.

BACKGROUND: Kwashiorkor is the edematous form of protein-energy malnutrition. It is associated with extreme poverty in developing countries and with chronic malabsorptive conditions such as cystic fibrosis in developed countries. Rare cases of kwashiorkor in affluent countries unrelated to chronic illness have been reported. We present 12 cases of kwashiorkor unrelated to chronic illness seen over 9 years by pediatric dermatologists throughout the United States, and discuss common causative themes in this easily preventable condition. OBSERVATIONS: Twelve children were diagnosed as having kwashiorkor in 7 tertiary referral centers throughout the United States. The diagnoses were based on the characteristic rash and the overall clinical presentation. The rash consisted of an erosive, crusting, desquamating dermatitis sometimes with classic "pasted-on" scale-the so-called flaky paint sign. Most cases were due to nutritional ignorance, perceived milk intolerance, or food faddism. Half of the cases were the result of a deliberate deviation to a protein-deficient diet because of a perceived intolerance of formula or milk. Financial and social stresses were a factor in only 2 cases, and in both cases social chaos was more of a factor than an absolute lack of financial resources. Misleading dietary histories and the presence of edema masking growth failure obscured the clinical picture in some cases. CONCLUSIONS: Physicians should consider the diagnosis of kwashiorkor in children with perceived milk allergies resulting in frequent dietary manipulations, in children following fad or unorthodox diets, or in children living in homes with significant social chaos. The presence of edema and "flaky paint" dermatitis should prompt a careful dietary investigation.

Diet Fads↗
PubMed2000

Residual lesions after Kasabach-Merritt phenomenon in 41 patients.

BACKGROUND: Kasabach-Merritt phenomenon (KMP) is the association of a vascular tumor and thrombocytopenic coagulopathy. Vascular tumors are either kaposiform hemangioendothelioma or tufted angioma but not "true" common hemangioma of infancy. There is a conspicuous absence in the literature regarding the late outcome and possible residual lesions after apparent clinical cure of KMP. OBJECTIVE: The purpose of the study was to analyze these residua in a large number of patients. METHODS: Clinical data on 41 patients who had KMP were accrued in an international cooperative study. The emphasis was on the residual lesions after resolution of the thrombocytopenia and other coagulation abnormalities. Imaging studies (follow-up magnetic resonance imaging studies available for 10 patients) and histologic specimens (30 specimens available for 26 patients, 18 biopsies done during the KMP and 12 concerning the sequelae) were reviewed. RESULTS: Residual lesions after "cure" of KMP were common. They exhibited 3 clinical patterns: type I lesions (n = 28) showed a cutaneous red stain, with or without associated red papules. The stain might overlap a minor fibrotic infiltration or a significant poorly delineated diffuse fibrotic infiltration. These cutaneous vascular lesions varied in size and appearance over time and were occasionally painful. Type II lesions were telangiectatic streaks and swelling (n = 5), and type III lesions showed a minor, firm, irregular, subcutaneous mass assessed by palpation or deep infiltration evidenced by computed tomography or magnetic resonance imaging (n = 8). A fourth feature was sequelae in muscles and/or joints. Histologically, tufted angioma was more common in the specimens from residual lesions, whereas kaposiform hemangioendothelioma was more common during the active phase of KMP. Imaging findings were remarkably reproducible and revealed a persistent vascular tumor. CONCLUSION: Residua of tumors associated with KMP are common after the resolution of thrombocytopenia and coagulopathy. They are (more or less) prominent dormant vascular tumors, not "scars" and, clinically as well as histologically, they differ markedly from involuted hemangioma.

Adolescent↗
PubMed2000

Vascular tumors and vascular malformations: evidence for an association.

BACKGROUND: The International Society for the Study of Vascular Anomalies classification is an updated biologic classification that distinguishes vascular tumors from vascular malformations on the basis of clinical and histologic characteristics and biologic behavior. OBJECTIVE: We propose that in a minority of cases there is an association between vascular tumors and vascular malformations. METHODS: We retrospectively identified clinical cases in our medical centers and others reported in the medical literature that demonstrate an association between vascular tumors and vascular malformation clinically or histologically. RESULTS: We identified several clinical or histologic settings in which vascular tumors and vascular malformations were associated: (1) coexistence of hemangioma and vascular malformation at the same anatomic site or in close proximity; (2) pyogenic granuloma arising within a vascular malformation; (3) hemangioma associated with developmental vascular anomalies; (4) spindle-cell hemangioendothelioma and venous malformation; (5) kaposiform hemangioendothelioma and lymphatic malformation. CONCLUSION: The biologic classification of vascular birthmarks distinguishing vascular tumors from vascular malformations is clinically useful and forms the framework for our understanding of vascular anomalies. These examples suggest that in a small minority of patients there is an association between vascular tumors and vascular malformations.

Cardiovascular Abnormalities↗
PubMed1999

Oral and genital ulceration: a unique presentation of immunodeficiency in Athabascan-speaking American Indian children with severe combined immunodeficiency.

BACKGROUND: Oral and genital ulcerations have been previously reported in 3 Navajo children diagnosed with severe combined immunodeficiency disease with T- and B-cell lymphopenia (T-B(-)-SCID). OBJECTIVE: To evaluate the occurrence of oral and genital ulcerations in 12 Athabascan-speaking American Indians with a diagnosis of T-B(-)-SCID (SCIDA group) and to compare their occurrence in non-Athabascan-speaking children with SCID (control group). We also observed the course of these ulcerations in response to bone marrow transplantation (BMT). DESIGN: Retrospective survey of the medical records of patients with SCID admitted from December 1, 1986, through July 31, 1995. SETTING: Pediatric Bone Marrow Transplantation Division at a university hospital. PATIENTS: Twelve children in the SCIDA group and 21 in the control group. All patients had virtual absence of T- and B-cell numbers and function at time of diagnosis. RESULTS: Oral and/or genital ulcers developed as a presenting feature of the SCIDA group. These ulcerations were not observed in the 21 controls. All patients underwent BMT. Of the 10 patients with oral and/or genital ulcerations, 3 had poor T-cell reconstitution after BMT, with recurrences of ulcers requiring additional BMTs. CONCLUSIONS: Oral and/or genital ulcerations are common in Athabascan-speaking American Indian children with T-B(-)-SCID but are not seen in non-Athabascan-speaking children with SCID. Thus, oral and/or genital ulceration appears to be an important, distinctive finding, and often a presenting feature of immunodeficiency in Athabascan-speaking American Indian children with SCID. Bone marrow transplantation with successful T-cell engraftment appears to be curative in the resolution of the ulcers, with recurrences only in patients who had poor T-cell reconstitution.

Bone Marrow Transplantation↗