Afshin Hatami

Treatment of Periocular Infantile Hemangiomas with Propranolol: Case Series of 18 Children

PURPOSE To study the efficacy of propranolol in the treatment of periocular infantile hemangiomas (IHs). DESIGN Retrospective interventional case series. PARTICIPANTS Eighteen children presenting periocular IH with occlusion of the pupil, anisometropic astigmatism, proliferating eyelid IH, or cosmetically disfiguring periocular IH. METHODS All patients received treatment with propranolol started at 0.5 mg/kg/day with an incremental increase by 0.5 mg/kg/day every 4 days, up to a maximum of 2 to 3 mg/kg/day. Complete eye examinations and serial photographs were obtained before, during, and after treatment. Doppler ultrasound and magnetic resonance imaging performed pre- and post-treatment were compared when available. MAIN OUTCOME MEASURES Evolution of the treated IH was evaluated with respect to astigmatism, amblyopia, and size of the lesion. RESULTS The IH size decreased in 17 of 18 patients. We noted a greater reduction when treatment was administered during the proliferative phase of growth of IHs. At the conclusion of treatment, none of our patients had amblyopia. The mean value of amblyogenic astigmatism (n = 7) decreased from 2.71 diopters (D) pretreatment to 1.03 D post-treatment. On radiology, 8 patients had significant regression of the lesion size of their IH and 1 patient had a limited progression. Propranolol had to be temporarily discontinued in only 1 patient because of symptomatic hypotension. CONCLUSIONS Propranolol seems to be an effective modality of treatment for periocular IH. It seems to be most efficacious when initiated in the proliferative phase of IH but may be beneficial even in the later stage. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Large congenital melanocytic nevi and neurocutaneous melanocytosis: One pediatric center's experience

BACKGROUND Large congenital melanocytic nevi (LCMN) predispose to neurocutaneous melanocytosis (NCM), which is associated with significant morbidity and mortality. OBJECTIVE To identify risk factors for NCM in patients with LCMN and suggest guidelines for their management. METHODS Medical records of patients with LCMN were reviewed at Sainte-Justine Hospital between 1980 and 2006. Presence of multiple satellite nevi and posterior midline location were evaluated as risk factors for NCM using chi-square test. Magnetic resonance imaging scans were reviewed by a neuroradiologist. RESULTS Twenty-six of 52 patients underwent radiologic investigation. Six of 26 (23%) had NCM. Patients with this condition are more likely to have multiple satellite nevi (100% vs 50%, P = .03) and have a trend to posterior midline location of their LCMN (100% vs 60%, P = .08). Patients with NCM are more likely to have both multiple satellite nevi and posterior midline location (100% vs 25%, P = .002). Radiologic findings are also presented. LIMITATIONS This was a retrospective case series with imprecise chart data in 38% of cases. CONCLUSION The presence of multiple satellite nevi alone or with associated posterior midline location of LCMN is associated with a higher risk of NCM. We recommend magnetic resonance imaging testing before 4 months of age in patients with these features.

Short- and long-term outcome of linear morphoea in children

Linear morphoea (LM) is a rare fibrosing disorder of the limbs or the face that may cause functional disability and severe aesthetic sequelae. Despite a wide range of therapeutics reported for LM, there is currently a lack of consensus on the optimal therapy. Little is known about the long‐term outcome of this disease.

Connective tissue nevi in children: Institutional experience and review

BACKGROUND Connective tissue nevi (CTN) are circumscribed hamartomas of the skin in which there is an abnormal mixture of normal components of the dermis that may be sporadic or associated with syndromes such as Buschke-Ollendorff, tuberous sclerosis, and Proteus. OBJECTIVE We sought to specify the clinical and histologic features of CTN in childhood and to propose a diagnostic approach and updated classification. METHODS This was a retrospective study in a tertiary pediatric outpatient population, accessing clinical and histopathological records. RESULTS We classified 114 cases of CTN from 1980 to 2008. LIMITATIONS The majority of cases were confirmed by histopathological examination. Therefore, our series excludes many CTN that were not biopsied. In addition, follow-up was variable. CONCLUSION Our series demonstrates the usefulness of a modified classification for CTN. Biopsy should be done when clinical diagnosis is uncertain, or in multiple lesions. When biopsy is performed it should include normal-appearing skin for comparison and, in Buschke-Ollendorff syndrome, limited anterior-posterior x-rays of the hands, wrists, feet, ankles, knees, and pelvis instead of a full skeletal survey.

Targetoid hemosiderotic hemangiomas (hobnail hemangiomas) are vascular lymphatic malformations: A study of 12 pediatric cases

BACKGROUND Targetoid hemosiderotic hemangioma (THH), also called hobnail hemangioma, is a benign vascular lesion and thought to be of lymphatic origin. OBJECTIVE We sought to perform a clinicopathologic analysis of cases diagnosed as THH in a tertiary care childrens hospital. METHODS Clinical and histopathologic data were obtained from a chart review of 12 confirmed pediatric cases of THH. To determine the presence or absence of lymphatic vessels in lesional biopsy specimens, we evaluated the expression of the lymphatic endothelial cell marker podoplanin using the D2-40 antibody. Wilms tumor-1 gene immunostaining and Ki-67 proliferation index were also performed to evaluate the proliferative nature of these lesions. RESULTS Three children had a lesion since birth and 4 had a history of trauma before appearance of the THH. D2-40 immunostaining was positive in every case. Wilms tumor-1 gene immunostaining was negative in 9 cases, focally positive in two cases, and not performed in one case. The Ki-67 proliferation index was very low in all cases studied. LIMITATIONS The small number of cases and restriction to a pediatric population were limitations. CONCLUSION Our findings suggest that THH should be classified as a lymphatic vascular malformation.

Expression of the senescence marker p16INK4a in skin biopsies of acute lymphoblastic leukemia survivors: a pilot study

BackgroundMost childhood cancer survivors will develop ionizing radiation treatment-related health conditions that, in many instances, resemble age-associated pathologies. Treatment-induced premature senescence could be an underlying mechanism.FindingsHere we wanted to know whether the expression of p16INK4a, a senescence/aging biomarker, is increased in skin biopsies of acute lymphoblastic leukemia survivors (ALL), previously exposed to chemotherapy and radiation therapy. Several years post-treatments, we found p16INK4a mRNA levels are 5.8 times higher in scalp skin biopsies (targeted by cranial irradiation therapy) compared to buttocks skin biopsies (n = 10, p = 0.01).ConclusionsThese results demonstrate for the first time that premature senescence is induced in pediatric cancer survivors and that p16INK4a expression could be used as a potential biomarker in this population.

Therapy of ulcerated hemangiomas.

Background: Cutaneous ulceration is the most common complication of infantile hemangiomas (IHs) seen in a pediatric dermatology practice. Objective: The most effective treatments in our experience are compared to those in the current literature. Methods: The study was a retrospective chart review of therapy of 169 ulcerated IHs at a tertiary care pediatric hospital and a literature review. Results: Combination therapy was the rule. Local wound care was required in all, pain management in 72%, pulsed dye laser in 42%, infection control in 38%, diminution of the hemangioma through systemic therapy in 36%, and suppression of bleeding in 2%. Limitations: A retrospective review compared to a case-control study has inherent bias. In addition, our cases were all at a tertiary referral center. Conclusion: All ulcerated IHs benefit from local barrier creams or dressings. Pulsed dye laser, antibiotics, topical morphine 0.1% in hydrogel, topical becaplermin, and, most importantly, systemic therapy (especially propranolol) to reduce the hemangioma may be useful.

Aortic Dilatation Associated With a De Novo Mutation in the SOX18 Gene: Expanding the Clinical Spectrum of Hypotrichosis-Lymphedema-Telangiectasia Syndrome

BACKGROUND We report a 13-year-old female patient followed since birth for multiple rare congenital defects, including hypotrichosis, telangiectasia, and severe dilatation of the ascending aorta. METHODS Comprehensive phenotype assessment throughout childhood included repeated echocardiographic measurements, evaluation of renal function, and immunohistochemical analysis of skin biopsy samples. Whole-exome sequencing was performed for the patient and both unaffected parents. RESULTS We identified a novel de novo mutation in the transcription factor SOX18 (c.481C>T:p.Gln161*) in the patient, which was absent in all unaffected family members. Echocardiography revealed early onset and progressive dilatation of the ascending aorta. Skin biopsy results confirmed the defects of the blood vasculature in the presence of intact lymphatic vessels. Assessment of renal function did not show any signs of renal problems or renal failure in the patient. CONCLUSIONS The genetic finding of a pathogenic SOX18 mutation enabled the diagnosis of the rare hypotrichosis-lymphedema-telangiectasia syndrome in our patient. The identification of a novel stop gain mutation in the SOX18 gene in association with dilatation of the aorta highlights the importance of this gene during the development of the circulatory system. Our study highlights the importance of whole-exome sequencing in the rapid identification of genes and gene mutations involved in rare conditions and thus expanding the knowledge and spectrum of clinical manifestations associated with them.

Childhood linear IgA bullous disease induced by trimethoprim-sulfamethoxazole.

BACKGROUND Linear IgA bullous disease (LABD) is a rare mucocutaneous autoimmune subepidermal blistering disease that can affect children mostly of pre-school age. As many as two-thirds of LABD are related to drug ingestion, particularly certain antibiotics, non-steroidal anti-inflammatory drugs and diuretics. MAIN OBSERVATION We describe a 3-year-old boy who presented a CMV infection followed by LABD induced by trimtheporim-sulfametoxazole. To our knowledge, this is the first reported case of trimethoprim-sulfamethoxazole that was confirmed by a rechallenge. CONCLUSIONS Most cases of drug-induced LABD are patients being treated with multiple systemic drugs that could induce the LABD. In the lack of suitable alternative treatment, the identification of the causative drug can be achieved by a rechallenge under close medical surveillance.

Diseases of Abnormal Sensitivity to Cold in Children on Psychostimulant Drugs

Background Oral psychostimulant (PS) drugs, the pharmacologic treatment of choice for attention-deficit/hyperactivity disorder (ADHD), have been associated with diseases of abnormal sensitivity to cold (DASC) such as Raynaud phenomenon and acrocyanosis. Objectives In a cohort of pediatric patients with DASC, we sought to identify prevalence and clinical features of patients on PS drugs. Methods A 6-year retrospective chart review (2005-2011) of Ste-Justine University Hospital Center DASC patients with and without exposure to PS drugs was performed. Clinical data were analyzed with descriptive statistical methods. Results Of 43 patients with DASC, 11 (25%) were exposed to PS drugs. In this group males were overrepresented, there was no evidence of collagen vascular diseases, serologic findings were not significant and the mean duration of PS intake was of 2.5 years. DASC age of onset was similar in both exposed and nonexposed patients. The incidence of more than one DASC type was greater in teenager patients with a positive family history of autoimmune and/or collagen vascular diseases. Limitations This study is limited by its small population size, short follow-up period and its retrospective nature. Conclusion Physicians should be aware of PS drugs as possible triggers for DASC.