Sheilagh Maguiness

“Eczema Coxsackium” and Unusual Cutaneous Findings in an Enterovirus Outbreak

OBJECTIVE: To characterize the atypical cutaneous presentations in the coxsackievirus A6 (CVA6)–associated North American enterovirus outbreak of 2011–2012. METHODS: We performed a retrospective case series of pediatric patients who presented with atypical cases of hand, foot, and mouth disease (HFMD) from July 2011 to June 2012 at 7 academic pediatric dermatology centers. Patients were included if they tested positive for CVA6 or if they met clinical criteria for atypical HFMD (an enanthem or exanthem characteristic of HFMD with unusual morphology or extent of cutaneous findings). We collected demographic, epidemiologic, and clinical data including history of skin conditions, morphology and extent of exanthem, systemic symptoms, and diagnostic test results. RESULTS: Eighty patients were included in this study (median age 1.5 years, range 4 months–16 years). Seventeen patients were CVA6-positive, and 63 met clinical inclusion criteria. Ninety-nine percent of patients exhibited a vesiculobullous and erosive eruption; 61% of patients had rash involving >10% body surface area. The exanthem had a perioral, extremity, and truncal distribution in addition to involving classic HFMD areas such as palms, soles, and buttocks. In 55% of patients, the eruption was accentuated in areas of eczematous dermatitis, termed “eczema coxsackium.” Other morphologies included Gianotti-Crosti–like (37%), petechial/purpuric (17%) eruptions, and delayed onychomadesis and palm and sole desquamation. There were no patients with serious systemic complications. CONCLUSIONS: The CVA6-associated enterovirus outbreak was responsible for an exanthem potentially more widespread, severe, and varied than classic HFMD that could be confused with bullous impetigo, eczema herpeticum, vasculitis, and primary immunobullous disease.

Risk for PHACE Syndrome in Infants With Large Facial Hemangiomas

OBJECTIVES: This study was conducted to determine the prevalence of posterior fossae of the brain, arterial anomalies, cardiac anomalies, and eye anomalies (PHACE) in infants with large facial hemangiomas. The extracutaneous manifestations of PHACE may be associated with significant morbidity, and the prevalence of PHACE in patients with facial hemangiomas has not previously been reported. METHODS: A multicenter prospective study was conducted with 108 infants who had large facial hemangiomas and were systematically evaluated for manifestations of PHACE. The prevalence of PHACE and its extracutaneous manifestations in this cohort was calculated. The relationship between hemangioma distribution and the manifestations of PHACE was analyzed. RESULTS: Thirty-three (31%) of 108 had PHACE. Thirty of the 33 patients with PHACE had >1 extracutaneous finding. The risk for PHACE syndrome was higher in infants with larger hemangiomas and in those with hemangiomas that encompassed >1 facial segment. The most common extracutaneous anomalies observed in infants with PHACE were of the arteries of the cerebrovasculature (91%) and cardiac anomalies (67%). Upper face (frontotemporal and frontonasal) hemangiomas were commonly observed in infants with PHACE; isolated maxillary hemangiomas were rarely associated with PHACE. CONCLUSIONS: In infants with large facial hemangiomas, one-third have extracutaneous manifestations consistent with the diagnosis of PHACE syndrome, most commonly cerebrovascular and cardiovascular anomalies. The high prevalence of arterial anomalies in this cohort has implications for clinical management and future research regarding the pathophysiology of PHACE.

Propranolol in the Management of Airway Infantile Hemangiomas

OBJECTIVE To report our experience with propranolol in managing airway infantile hemangiomas. DESIGN Case series of 3 consecutive patients who had extensive, symptomatic airway infantile hemangiomas treated with propranolol. SETTING Tertiary academic medical center. PATIENTS Three infants with facial cutaneous hemangiomas who developed stridor that progressed to respiratory distress, which according to laryngoscopic examination results was confirmed to be caused by extensive subglottic hemangiomas. These patients underwent follow-up during their course of therapy, ranging from 3 weeks to 15 months. RESULTS Patient 1 failed to respond to systemic corticosteroids, laser ablation, and intravenous vincristine for her airway hemangioma and had to undergo tracheotomy. She was given propranolol after her tracheotomy and had a significant reduction in her subglottic airway obstruction. Patient 2 developed progressive stridor secondary to airway hemangioma at age 6 1/2 months following tapering of systemic corticosteroids prescribed for her periorbital hemangioma. Systemic corticosteroids were restarted with the addition of propranolol. The stridor improved within 24 hours, and she was able to be weaned off corticosteroids. Patient 3 was also treated with initial combined therapy of systemic corticosteroids and propranolol. He had a significant reduction in stridor within 24 hours and was weaned off corticosteroids. CONCLUSIONS Our 3 patients had severe respiratory symptoms related to their airway infantile hemangiomas. In the first patient, propranolol was used when other treatments were ineffective or associated with intolerable adverse effects. In the second and third patients, propranolol was part of a dual regimen that resulted in rapid resolution of airway symptoms and allowed for quicker weaning of corticosteroids.

Current Management of Infantile Hemangiomas

During the past several years, there have been new advancements in the management of infantile hemangiomas (IHs). In many patients, no treatment is ever necessary--because IHs are well known for their natural history of spontaneous involution. However, a significant minority of hemangiomas do require treatment. Moreover, they are very heterogeneous, making the decision of when, how, and why to intervene quite variable. The least common but most important rationale for intervention is the presence of a life- or function-threatening complication, where prompt therapeutic intervention is a necessity. A much more common scenario is ulceration, where appropriate management is needed to expedite healing and control pain. Increasingly, the life-altering aspects of hemangioma are being recognized as a rationale for treatment because permanent scarring and disfigurement can result even if involution is complete. Treatments for IHs currently include topical, intralesional, and systemic therapies. Laser and surgical modalities are also sometimes used depending on the clinical scenario. In the absence of rigorous evidence-based studies, clinicians must carefully weigh the risks and benefits of medical or surgical treatments versus observation alone in tailoring management to the specific clinical situation at hand.

Analysis of interleukin-10 levels in lesions of vitiligo following treatment with topical tacrolimus.

Background  Vitiligo is an acquired dermatological condition that is characterized by depigmentation of patches of skin. It is relatively common, occuring in about 0·38–0·50% of the general population, and can engender significant cosmetic disfigurement and psychological sequelae in the affected individual. Recent studies demonstrate that topical tacrolimus (Protopic®; Astellas, Markham, ON, Canada) is efficacious in the treatment of vitiligo. We propose that the successful treatment of vitiligo with topical tacrolimus involves the unique immunosuppressive actions of the T lymphocyte T‐helper (Th) 2 cytokine, interleukin (IL)‐10.

Management of difficult infantile haemangiomas

Infantile haemangiomas are common vascular tumours of infancy. They typically present shortly after birth, undergo a period of rapid proliferation, and then slowly involute over many years. Although most patients require no intervention, appropriate investigation and treatment may be necessary in a minority of cases. Identifying which patients require further investigation or intervention can be difficult due to the heterogeneity of clinical presentation. This is compounded by a lack of rigorous randomised controlled trials on haemangioma management. Therefore, the rationale for treatment is not always straightforward. Haemangiomas occur anywhere on the body, have superficial, deep or mixed morphology, and depending on anatomic location, size and subtype, can be associated with underlying structural anomalies and many other potential complications. Generally, the management of difficult haemangiomas is best approached on a case-by-case basis. Over the last few years, there have been several advances in our understanding of haemangiomas, together with some exciting new therapeutic options. In the following review, the authors discuss the various possible complications of infantile haemangiomas, the rationale for treatment and appropriate possible interventions.

Early White Discoloration of Infantile Hemangioma: A Sign of Impending Ulceration

OBJECTIVE To evaluate the relationship between early white discoloration of infantile hemangioma (IH) and ulceration. DESIGN Retrospective cohort study. SETTING Tertiary referral center. PATIENTS A case series of 11 infants with early white discoloration of IH are described. An additional 55 infants with IH, aged 3 months, were evaluated retrospectively from a photograph archive to further explore the relationship between early white discoloration and presence or development of ulceration. MAIN OUTCOME MEASURES Patient demographics and hemangioma size, location, and subtype are documented. Sensitivity and specificity of white discoloration in relationship to ulceration are estimated. RESULTS Ten of the 11 infants in the case series were girls (90%); all IHs were of segmental or indeterminate subtype. Average age at first ulceration was 2.6 months, with average age at healing 5.2 months. No intervention halted progression of ulceration. Of the 55 additional 3-month-old infants, 14 had white discoloration and 12 of these 14 had or developed ulceration (86%). When the hemangioma was either white or slightly white, sensitivity for predicting ulceration was 1.00 (95% confidence interval [CI], 0.78-1.00), with a specificity of 0.68 (95% CI, 0.51-0.81). In contrast, in infants with either slightly white or no white discoloration, the sensitivity for not developing ulceration was 0.80 (95% CI, 0.52-0.96), with a specificity of 0.95 (95% CI, 0.83-0.99), suggesting that a lack of substantial white discoloration early in infancy indicates low risk of ulceration. CONCLUSION Early white discoloration of infantile hemangioma is highly suggestive of impending ulceration.

Relevance of D-dimer Testing in Patients with Venous Malformations

tology Foundation, American Society for Dermatologic Surgery, National Psoriasis Foundation, Ortho Pharmaceuticals, Aventis Pharmaceuticals, Roche Dermatology, 3M, Bristol-Myers Squibb Dermatology, and Novartis. Funding/Support: The Center for Dermatology Research is funded by a grant from Galderma Laboratories, LP. Role of the Sponsors: The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; or in the preparation of the manuscript, review, or approval of the manuscript.

Management of capillary malformations

Capillary malformations (CMs) are the most common vascular malformations. They are comprised of the small vessels of the capillary network in skin and mucous membranes. In the vast majority of affected individuals, CMs are isolated and not associated with any underlying abnormalities. Depending on size and location, however, they may cause significant morbidity due to disfigurement or stigmatization and, rarely, herald the presence of an underlying syndrome.

Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy syndrome

Disorders of keratinization (DOK) show marked genotypic and phenotypic heterogeneity. In most cases, disease is primarily cutaneous, and further clinical evaluation is therefore rarely pursued. We have identified subjects with a novel DOK featuring erythrokeratodermia and initially-asymptomatic, progressive, potentially fatal cardiomyopathy, a finding not previously associated with erythrokeratodermia. We show that de novo missense mutations clustered tightly within a single spectrin repeat of DSP cause this novel cardio-cutaneous disorder, which we term erythrokeratodermia-cardiomyopathy (EKC) syndrome. We demonstrate that DSP mutations in our EKC syndrome subjects affect localization of desmosomal proteins and connexin 43 in the skin, and result in desmosome aggregation, widening of intercellular spaces, and lipid secretory defects. DSP encodes desmoplakin, a primary component of desmosomes, intercellular adhesion junctions most abundant in the epidermis and heart. Though mutations in DSP are known to cause other disorders, our cohort features the unique clinical finding of severe whole-body erythrokeratodermia, with distinct effects on localization of desmosomal proteins and connexin 43. These findings add a severe, previously undescribed syndrome featuring erythrokeratodermia and cardiomyopathy to the spectrum of disease caused by mutation in DSP, and identify a specific region of the protein critical to the pathobiology of EKC syndrome and to DSP function in the heart and skin.