Pre-eclampsia and risk of infantile haemangioma.

BACKGROUND: Infantile haemangioma is the most common tumour of infancy, but the association with pre-eclampsia is poorly understood. OBJECTIVES: We determined the relationship between variants of pre-eclampsia and risk of infantile haemangioma. METHODS: We carried out a retrospective cohort study of hospital data for all live births between 1989 and 2013 in Quebec, Canada. We identified 14 240 neonates with, and 1 930 564 without haemangioma before discharge, and determined whether early- or late-onset pre-eclampsia was documented on the maternal chart. We used log-binomial regression to compute prevalence ratios (PRs) and 95% confidence intervals (CIs) for the association between pre-eclampsia and infantile haemangioma, adjusted for maternal characteristics. RESULTS: The prevalence of any haemangioma was higher for pre-eclampsia than for no pre-eclampsia (81·3 vs. 72·9 per 10 000), with a PR of 1·15 (95% CI 1·06-1·25) after adjustment for maternal characteristics. Pre-eclampsia with onset before 34 weeks' gestation was associated with cutaneous (PR 2·32, 95% CI 1·68-3·21), noncutaneous (PR 3·66, 95% CI 2·49-5·37) and unspecified haemangioma (PR 2·49, 95% CI 1·77-3·49). However, the association between early-onset pre-eclampsia and haemangioma was attenuated once long neonatal length of hospital stays was accounted for. There was no association with late-onset pre-eclampsia after 34 weeks, and associations were weaker for other variants including severe pre-eclampsia and pre-eclampsia with low birthweight. CONCLUSIONS: Early-onset pre-eclampsia is associated with increased risk of haemangioma at birth, but detection bias due to longer hospital stays and closer follow-up may be part of the reason.

Risk factors for morphoea disease severity: a retrospective review of 114 paediatric patients.

BACKGROUND: Morphoea is a rare fibrosing disease of the skin and subcutaneous tissue with an unpredictable disease course, running the spectrum from mild skin involvement to severe disfigurement or extracutaneous complications. OBJECTIVES: Our objective was to describe the natural history of paediatric morphoea and determine patient variables that were associated with severe disease. PATIENTS AND METHODS: We conducted a retrospective chart review of patients with morphoea seen in one paediatric hospital system. Information about demographics, clinical characteristics, disease course and treatment were collected. Statistical analysis was performed using appropriate univariate tests and a multivariable model. RESULTS: One hundred and fourteen patients met study inclusion criteria. The female : male ratio was 2·6 : 1, and the median age of onset was 7 years old. There were 55 patients (48%) with linear morphoea, 38 patients (33%) with circumscribed morphoea, 12 patients (11%) with generalized morphoea, and nine patients (8%) with mixed morphoea. Neurological symptoms and joint involvement were present in 27 subjects (24%). Extracutaneous manifestations occurred in 38% of subjects with linear morphoea, compared with 15% with generalized morphoea and 3% with circumscribed morphoea (P = 0·0001). Thirty-six per cent of children with disease onset prior to 10 years of age and 5% of children with disease onset after 10 years of age had extracutaneous manifestations (P = 0·0002). Both linear morphoea and early-onset disease were significantly associated with extracutaneous involvement in a multivariable model. CONCLUSIONS: Children with linear morphoea and disease onset before 10 years of age should be monitored closely for extracutaneous manifestations and need early treatment with systemic medications to prevent disease complications.

Demographic and clinical characteristics of cutaneous lupus erythematosus at a paediatric dermatology referral centre.

BACKGROUND: Paediatric cutaneous lupus erythematosus (CLE) is uncommon and inadequately described in the literature. Similar to adults, children with CLE develop LE-specific and/or LE-nonspecific skin findings. Similarities and differences in demographics and clinical course between paediatric and adult CLE have not been sufficiently described. OBJECTIVES: To detail the demographic and clinical features of paediatric CLE and compare these findings with those reported in the adult literature. METHODS: A retrospective chart review was performed of 53 children seen in a paediatric dermatology clinic with cutaneous manifestations of LE. RESULTS: Patients presented with all five major subtypes of CLE, with some notable differences from adult CLE and previously published reports of paediatric CLE. Progression from discoid LE to systemic LE (SLE) did not occur in our cohort. Patients with subacute CLE were more likely than adults to have lesions below the waist as well as concomitant SLE. Sex distribution for CLE in our study was equal prior to puberty and female predominant in post-pubertal patients. CONCLUSIONS: Children with CLE have variable clinical presentations and progression to SLE that may be different from adult disease. Specifically, children with acute and subacute CLE may be more likely than adults to have systemic disease; therefore, patients with these subtypes should be monitored closely for evidence of SLE. Study limitations included small patient numbers that may limit the ability to generalize these data and relatively short follow-up intervals.

The hair collar sign: marker for cranial dysraphism.

OBJECTIVE: To call attention to a cutaneous marker for neural tube closure defects of the scalp, the "hair collar" sign. This finding consists of a ring of long, dark, coarse hair surrounding a midline scalp nodule. METHODS AND RESULTS: Four children with small congenital scalp nodules and the hair collar sign were studied from the standpoint of clinical findings, radiologic scans, and histology of the excised nodules. All four had an overlying vascular stain in addition to the hair collar. Patients 1 and 2 were found to have encephaloceles, and one had heterotopic brain tissue. The fourth family refused surgery, but the clinical and radiologic findings were consistent with a diagnosis of atretic encephaloceles. One infant had agenesis of the corpus callosum and a Dandy-Walker malformation as associated findings. CONCLUSIONS: The "hair collar" sign should alert the pediatrician to the possibility of ectopic neural tissue in the scalp and/or underlying central nervous system malformations.

Dyskeratosis congenita with linear areas of severe cutaneous involvement.

Dyskeratosis congenita (DC) is a rare hereditary disorder of skin which may be associated with aplastic anemia. The pattern of inheritance is X-linked recessive in most instances, but autosomal dominant and autosomal recessive types have been documented. Reticulated hyperpigmentation usually is the first manifestation. The pigmentary changes may be limited to neck, upper chest, and proximal parts of the limbs initially but within affected areas the involvement is always diffuse. We report on a patient with typical diffuse cutaneous signs of dyskeratosis congenita superimposed with hyperpigmentation that was more pronounced along Blaschko's lines. To explain this phenomenon, we assume that the patient has the autosomal dominant type and that loss of heterozygosity occurred in a somatic cell giving rise to a population of cells that migrated along these lines during embryogenesis.

Preauricular skin defects. A consequence of a persistent ectodermal groove.

BACKGROUND: The term aplasia cutis is used to describe congenital localized defects of the skin. This affliction is the end result of various in utero events. Aplasia cutis of the face, although rare, has been associated with numerous dysmorphic features and described under many clinical terms. OBSERVATIONS: We studied 10 patients with oval, atrophic patches distributed in a linear pattern on the preauricular region of the face. Most of the defects were bilateral, and all consistently fell in an oblique line extending from the preauricular region to the angle of the mouth. This line corresponds to the region of fusion between the maxillary and mandibular facial prominences during embryonic development. CONCLUSIONS: This type of facial aplasia cutis may be the result of incomplete fusion of the ectodermal groove between the maxillary and mandibular facial prominences. Although other types of facial skin defects may share a similar pathogenic mechanism, they are distinct in that they occur in different regions and may have other abnormal facial features.

Vesiculopustular eruptions in Down syndrome neonates with myeloproliferative disorders.

BACKGROUND: Infants with Down syndrome are at increased risk for hematologic abnormalities, including leukemoid reaction, transient myeloproliferative disorder, and congenital leukemia. The differential diagnosis of a vesiculopustular eruption in an infant with Down syndrome and these hematologic abnormalities is broad and includes benign, self-limited disorders as well as life-threatening infections. OBSERVATION: We describe 3 newborns with Down syndrome and vesiculopustular eruptions associated with myeloproliferative disorders during the neonatal period. These lesions differ from other neonatal vesicular eruptions in that they have a unique distribution, display pathergy, and contain immature hematopoietic cells similar to circulating blast cells. Resolution occurs without treatment as the hematologic disorder subsides. CONCLUSIONS: Infants with Down syndrome and hematologic abnormalities may have a cutaneous eruption that has characteristic clinical and histopathologic findings. It is possible that this eruption has been unrecognized in the past because of its self-limited course. Whether this eruption is a prognostic factor for the subsequent development of leukemia is uncertain.

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.

Cutaneous signs of neural tube dysraphism.

Cutaneous markers have a crucial role in the detection and diagnosis of occult neural tube dysraphism. Recognition of these stigmata and appropriate radiologic imaging decrease the long-term morbidity of this condition.

X Chromosome-Inactivation Patterns in 31 Individuals with PHACE Syndrome.

Segmental hemangiomas of the head and neck can be associated with multiple congenital anomalies in the disorder known as PHACE syndrome (OMIM 606519) (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, and eye anomalies). All reported cases of PHACE syndrome to date have been sporadic, and the genetic basis of this disorder has not yet been established. PHACE syndrome has a striking female predominance which has raised the question of X-linked inheritance. In this study, the X chromosome-inactivation (XCI) patterns of 31 females with PHACE syndrome and their mothers were analyzed using blood-derived DNA and X-chromosome locus methylation assay. This study was performed to test the hypothesis that some cases of PHACE syndrome are due to X-linked inheritance and favorable skewing in the mothers may protect against a severe phenotype, but the clinical phenotype may be unmasked in daughters with a random pattern of X-inactivation. XCI analysis was informative in 27/31 mothers. Our results identified skewed XCI in 5 of 27 (19%) informative mothers, which is not statistically significant with a p value of 0.41. None of the mothers reported significant medical problems, although a full PHACE work-up has not been performed in these individuals. Skewed XCI in the mothers of children with PHACE was identified in only a minority of cases. Based on these results, genetic heterogeneity is likely in PHACE syndrome, although it is possible a subset of cases are caused by a mutation in an X-linked gene.

Cervical and intracranial arterial anomalies in 70 patients with PHACE syndrome.

BACKGROUND AND PURPOSE: Cerebral and cervical arterial abnormalities are the most common non-cutaneous anomaly in PHACE syndrome, but the location and type of arterial lesions that occur have not been systematically assessed in a large cohort. Our aim was to characterize the phenotypic spectrum of arteriopathy, assess the frequency with which different arteries are involved, and evaluate spatial relationships between arteriopathy, brain structural lesions, and hemangiomas in PHACE syndrome. MATERIALS AND METHODS: Intracranial MRA and/or CTA images from 70 children and accompanying brain MR images in 59 patients with arteriopathy and PHACE syndrome were reviewed to identify the type and location of arterial lesions and brain abnormalities. Five categories of arteriopathy were identified and used for classification: dysgenesis, narrowing, nonvisualization, primitive embryonic carotid-vertebrobasilar connections, and anomalous arterial course or origin. Univariate logistic regression analyses were performed to test for associations between arteriopathy location, hemangiomas, and brain abnormalities. RESULTS: By study design, all patients had arterial abnormalities, and 57% had >1 form of arteriopathy. Dysgenesis was the most common abnormality (56%), followed by anomalous course and/or origin (47%), narrowing (39%), and nonvisualization (20%). Primitive embryonic carotid-vertebrobasilar connections were present in 20% of children. Hemangiomas were ipsilateral to arteriopathy in all but 1 case. The frontotemporal and/or mandibular facial segments were involved in 97% of cases, but no other specific associations between arteriopathy location and hemangioma sites were detected. All cases with posterior fossa anomalies had either ICA anomalies or persistent embryonic carotid-basilar connections. CONCLUSIONS: The arteriopathy of PHACE syndrome commonly involves the ICA and its embryonic branches, ipsilateral to the cutaneous hemangioma, with dysgenesis and abnormal arterial course the most commonly noted abnormalities. Brain abnormalities are also typically ipsilateral.

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.

Role of human papillomavirus in cutaneous oncogenesis.

There is a strong association between the human papillomavirus and cutaneous squamous cell carcinoma. If this association was merely random, one would expect an equal distribution of human papillomavirus types among affected individuals. However, only specific types of human papillomavirus are consistently found in cutaneous and genital squamous cell carcinomas. Immunosuppressed individuals clearly have a much higher incidence of cutaneous carcinomas. Immunosuppression, either local or systemic, not only decreases immune surveillance but may also dictate the amount and type of virus each individual may carry. Epidermodysplasia verruciformis and other rare hereditary disorders that combine specific immune defects and an increased incidence of malignancy are very useful models that clearly fulfill a multistep theory of oncogenesis. The precise mechanism of oncogenesis in these select human papillomavirus types is not yet fully understood. Intracellular interactions with the recently described tumor suppressor proteins may prove to be the primary site of action of these oncogenic viruses. Environmental cocarcinogens and activation of oncogenes are clearly important if not essential factors in human papillomavirus-associated tumors. As our knowledge and understanding of malignant transformation grows, it becomes apparent that this is a complex multistep process.