Marcia Hogeling

A Randomized Controlled Trial of Propranolol for Infantile Hemangiomas

OBJECTIVE: Propranolol hydrochloride is a safe and effective medication for treating infantile hemangiomas (IHs), with decreases in IH volume, color, and elevation. METHODS: Forty children between the ages of 9 weeks and 5 years with facial IHs or IHs in sites with the potential for disfigurement were randomly assigned to receive propranolol or placebo oral solution 2 mg/kg per day divided 3 times daily for 6 months. Baseline electrocardiogram, echocardiogram, and laboratory evaluations were performed. Monitoring of heart rate, blood pressure, and blood glucose was performed at each visit. Children younger than 6 months were admitted to the hospital for monitoring after their first dose at weeks 1 and 2. Efficacy was assessed by performing blinded volume measurements at weeks 0, 4, 8, 12, 16, 20, and 24 and blinded investigator scoring of photographs at weeks 0, 12, and 24. RESULTS: IH growth stopped by week 4 in the propranolol group. Significant differences in the percent change in volume were seen between groups, with the largest difference at week 12. Significant decrease in IH redness and elevation occurred in the propranolol group at weeks 12 and 24 (P = .01 and .001, respectively). No significant hypoglycemia, hypotension, or bradycardia occurred. One child discontinued the study because of an upper respiratory tract infection. Other adverse events included bronchiolitis, gastroenteritis, streptococcal infection, cool extremities, dental caries, and sleep disturbance. CONCLUSION: Propranolol hydrochloride administered orally at 2 mg/kg per day reduced the volume, color, and elevation of focal and segmental IH in infants younger than 6 months and children up to 5 years of age.

Propranolol: useful therapeutic agent for the treatment of ulcerated infantile hemangiomas

Infantile hemangioma (IH) is the most common vascular tumor in early childhood. Ulceration is the most frequent complication, and its management can be challenging. We present 6 cases of ulcerated IH at a single pediatric center, which responded to oral propranolol within 2 to 6 weeks. We recommend that oral propranolol therapy be considered for the management of ulcerated IH as first-line treatment.

Extensive subcutaneous fat necrosis of the newborn associated with therapeutic hypothermia.

Abstract:  Subcutaneous fat necrosis of the newborn is a form of panniculitis that most often occurs in full‐term infants with predisposing risk factors. Three neonates with hypoxic ischemic encephalopathy were treated with therapeutic hypothermia and developed extensive subcutaneous fat necrosis. All three infants developed extensive subcutaneous fat necrosis, involving the back, scalp, and arms. Mild, asymptomatic hypercalcemia was noted in one infant in the weeks following the subcutaneous fat necrosis. Hypothermia as a risk factor for subcutaneous fat necrosis is reviewed. Clinicians should be aware of subcutaneous fat necrosis as a possible risk factor and complication associated with asphyxiated newborns who may undergo therapeutic hypothermia. Future studies for therapeutic hypothermia should evaluate neonates for the development of subcutaneous fat necrosis.

Forehead pressure necrosis in neonates following continuous positive airway pressure.

Abstract:  After treatment with continuous positive airway pressure (CPAP) via nasal masks and a face mask, three neonates developed pressure necrosis involving their central forehead and left eyebrow. The pressure necrosis resulted in permanent scarring in all three infants. We describe a case series of a new cutaneous iatrogenic complication of CPAP.

Lymphatic malformations: clinical course and management in 64 cases.

Background:  Lymphatic malformations (LM) are rare vascular malformations.

Safety of Systemic Agents for the Treatment of Pediatric Psoriasis

Importance Use of systemic therapies for moderate to severe psoriasis in children is increasing, but comparative data on their use and toxicities are limited. Objective To assess patterns of use and relative risks of systemic agents for moderate to severe psoriasis in children. Design, Setting, and Participants A retrospective review was conducted at 20 centers in North America and Europe, and included all consecutive children with moderate to severe psoriasis who used systemic medications or phototherapy for at least 3 months from December 1, 1990, to September 16, 2014. Main Outcomes and Measures The minimal core data set included age, sex, severity of psoriasis, systemic interventions, monitoring, adverse events (AEs), and reason for discontinuation. Results For 390 children (203 girls and 187 boys; mean [SD] age at diagnosis, 8.4 [3.7] years) with psoriasis who used 1 or more systemic medications, the mean interval between diagnosis and starting systemic therapy was 3.0 years. Methotrexate was used by 270 patients (69.2%), biologic agents (primarily etanercept) by 106 (27.2%), acitretin by 57 (14.6%), cyclosporine by 30 (7.7%), fumaric acid esters by 19 (4.9%), and more than 1 medication was used by 73 (18.7%). Of 270 children taking methotrexate, 130 (48.1%) reported 1 or more AEs associated with methotrexate, primarily gastrointestinal (67 [24.8%]). Folic acid 6 days per week (odds ratio, 0.16; 95% CI, 0.06-0.41; P < .001) or 7 days per week (OR, 0.21; 95% CI, 0.08-0.58; P = .003) protected against gastrointestinal AEs more than once-weekly folic acid, regardless of the total weekly dosage. Methotrexate-associated hepatic transaminase elevations were associated with obesity (35 of 270 patients [13.0%]), but a folic acid regimen was not. Injection site reactions occurred in 20 of 106 patients (18.9%) treated with tumor necrosis factor inhibitors, but did not lead to discontinuation of treatment. Having 1 or more AEs related to medication, gastrointestinal AE, laboratory abnormality, or AE leading to discontinuation of the drug was more likely with methotrexate than tumor necrosis factor inhibitors, but having 1 or more infections related to medication (predominantly upper airway) was less likely. Six patients developed a serious treatment-related AE (methotrexate, 3; fumaric acid esters, 2; and adalimumab, 1), but methotrexate and biologic agents were taken for a mean duration that was 2-fold greater than the mean duration for cyclosporine or fumaric acid esters. No patient developed tuberculosis or a malignant neoplasm. Conclusions and Relevance Medication-related AEs occur less often with tumor necrosis factor inhibitors than with methotrexate. Folic acid administration 6 or 7 times per week protected more against methotrexate-induced gastrointestinal AEs than did weekly administration. A prospective registry is needed to track the long-term risks of systemic agents for pediatric psoriasis.

Propranolol for Infantile Hemangiomas: A Review

Infantile hemangiomas (IHs) are the most common vascular tumors of infancy. Since it was discovered several years ago, propranolol hydrochloride has become a very popular and successful treatment for complicated and aesthetically disfiguring IHs. The recent literature on propranolol is reviewed, including a summary of larger studies, discussion of adverse effects, and the use of propranolol in complicated IHs, such as ulcerated IHs, airway, and hepatic IHs.

Severe neonatal congenital erythropoietic porphyria.

Abstract:  Congenital erythropoietic porphyria is a rare form of porphyria, presenting during the neonatal period or during infancy. Clinical features include photosensitive blistering and severe anemia. Wood’s lamp fluorescence of the diaper is a useful screening test. We describe a severely affected neonate with systemic involvement due to a homozygous mutation. Because of ongoing severe hemolytic anemia and severe photosensitivity, bone‐marrow transplantation was performed, but the patient ultimately succumbed to chemotherapy‐induced lung damage, as well as severe pulmonary hypertension, likely due to his chronic hemolytic anemia.

The changing face of complicated infantile hemangioma treatment

Infantile hemangiomas are the most common vascular tumors of infancy. A multidisciplinary approach including dermatologists, otolaryngologists, plastic surgeons, hematologists/oncologists and interventional/diagnostic radiologists is crucial for appropriate management of children with complicated infantile hemangiomas. Since its unforeseen discovery in 2008, propranolol has become the first-line treatment for infantile hemangiomas, eclipsing systemic corticosteroids and radiologic intervention. There are still, however, uncommon indications for more aggressive interventional management. We review the 2014-updated International Society for the Study of Vascular Anomalies (ISSVA) classification for vascular anomalies. Additionally, we suggest management algorithms for complicated lesions, including recommendations for radiologic and surgical intervention.

CARD14-associated papulosquamous eruption: A spectrum including features of psoriasis and pityriasis rubra pilaris

Background: Heterozygous mutations in caspase recruitment domain family member 14 gene (CARD14) have been shown to be associated with psoriasis and familial pityriasis rubra pilaris (PRP). Many subjects with CARD14 mutations display features of both disorders, which can result in diagnostic uncertainty. In addition, these eruptions are often recalcitrant to conventional psoriasis therapies such as methotrexate, oral retinoids, and tumor necrosis factor‐&agr; inhibitors. Objective: We sought to describe the clinical characteristics, family history, and response to therapy in subjects with papulosquamous eruptions due to mutations in CARD14. Methods: Subjects were referred for genetic testing as part of a registry of subjects with inherited disorders of keratinization. DNA was isolated from blood or saliva, and multiplex targeted sequencing or whole exome sequencing was performed. Clinical histories of subjects with CARD14 mutations were reviewed. Results: We identified 15 kindreds with CARD14‐associated papulosquamous eruption (CAPE). Characteristic features of CAPE include early age of onset; prominent involvement of the cheeks, chin, and ears; family history of psoriasis or PRP; minimal response to conventional topical and systemic psoriasis therapies; and improvement with ustekinumab. Limitations: Relatively small sample size. Conclusions: Many subjects with CARD14 mutations display characteristics of both psoriasis and PRP. We propose the term CARD14‐associated papulosquamous eruption to describe this spectrum of disease. Subjects with clinical features suggestive of CAPE should undergo CARD14 sequencing and may benefit from treatment with ustekinumab.