Marlies de Graaf

Adverse effects of propranolol when used in the treatment of hemangiomas: A case series of 28 infants

BACKGROUND Infantile hemangioma (IH) is a frequently encountered tumor with a potentially complicated course. Recently, propranolol was discovered to be an effective treatment option. OBJECTIVE To describe the effects and side effects of propranolol treatment in 28 children with (complicated) IH. METHODS A protocol for treatment of IH with propranolol was designed and implemented. Propranolol was administered to 28 children (21 girls and 7 boys, mean age at onset of treatment: 8.8 months). RESULTS All 28 patients had a good response. In two patients, systemic corticosteroid therapy was tapered successfully after propranolol was initiated. Propranolol was also an effective treatment for hemangiomas in 4 patients older than 1 year of age. Side effects that needed intervention and/or close monitoring were not dose dependent and included symptomatic hypoglycemia (n = 2; 1 patient also taking prednisone), hypotension (n = 16, of which 1 is symptomatic), and bronchial hyperreactivity (n = 3). Restless sleep (n = 8), constipation (n = 3) and cold extremities (n = 3) were observed. LIMITATIONS Clinical studies are necessary to evaluate the incidence of side effects of propranolol treatment of IH. CONCLUSIONS Propranolol appears to be an effective treatment option for IH even in the nonproliferative phase and after the first year of life. Potentially harmful adverse effects include hypoglycemia, bronchospasm, and hypotension.

Is cardiovascular evaluation necessary prior to and during beta-blocker therapy for infantile hemangiomas?: A cohort study.

BACKGROUND Although consensus guidelines for pretreatment evaluation and monitoring of propranolol therapy in patients with infantile hemangiomas (IH) have been formulated, little is known about the cardiovascular side effects. OBJECTIVES We sought to analyze cardiovascular evaluations in patients with IH at baseline and during treatment with an oral beta-blocker. METHODS Data from 109 patients with IH were retrospectively analyzed. Patient and family history, pretreatment electrocardiogram (ECG), heart rate, and blood pressure were evaluated before initiation of beta-blocker therapy. Blood pressure and standardized questionnaires addressing side effects were evaluated during treatment. RESULTS Questionnaire analyses (n = 83) identified 3 cases with a family history of cardiovascular disease in first-degree relatives. ECG findings were normal in each case and no serious complication of therapy occurred. ECG abnormalities were found in 6.5% of patients but there were no contraindications to beta-blocker therapy and no major complications. Hypotension in 9 patients did not require therapy adjustment. In all, 88 parents (81%) reported side effects during beta-blocker treatment. LIMITATIONS The relatively small patient cohort is a limitation. CONCLUSION Pretreatment ECG is of limited value for patients with an unremarkable cardiovascular history and a normal heart rate and blood pressure. Hypotension may occur during treatment.

Evaluation of the Compliance, Acceptance, and Usability of a Web-Based eHealth Intervention for Parents of Children With Infantile Hemangiomas: Usability Study

Background Infantile hemangiomas (IH) are common benign vascular tumors in children. Recognition and timely referral of high risk IH to specialized centers is important. This might be achieved by involving parents in the care for IH by means of an eHealth intervention. Objective The objective of our study was to evaluate parent compliance, acceptance, and usability of an open access, Web-based eHealth intervention (including e-learning and e-consult) designed to increase parents’ knowledge and (risk) evaluation of IH. Methods A cross-sectional study of parents who completed the eHealth intervention between October 2010 and November 2012 was carried out. All parents were sent a study questionnaire. Questions to evaluate compliance (to the advice given by a dermatologist during e-consultation) were asked. Acceptance and usability were evaluated by using the modified Technology Acceptance Model. Results A total of 224 parents completed the eHealth intervention and received the questionnaire, 135/224 parents responded (response rate was 60.3%). There were 128/135 questionnaires that were completed and included. A total of 110/128 (85.9%) parents were compliant to the advice of the dermatologist. There were 116.8/128 (91.3%) that perceived the eHealth intervention as useful and almost all parents (98.4%, 126/128) found the information in the e-learning clear. There were 29/128 (22.7%) that experienced technical problems. The majority of the parents (94.5%, 121/128) found the eHealth intervention reliable and most of them (98.4%, 126/128) would recommend the eHealth intervention to other parents. Noncompliant parents judged the eHealth intervention significantly less reliable compared to compliant parents (71%, 10/14 versus 97.3%, 107/110; P=.003). Conclusions Parents of children with an IH showed a high compliance (85.9%, 110/128) to the advice of the dermatologist given via our Web-based eHealth intervention. This high compliance might be positively influenced by the good acceptance and usability of the eHealth intervention and might result in timely presentation and treatment of children with high risk IH in specialized centers.

High-dose ustekinumab for severe childhood deficiency of interleukin-36 receptor antagonist (DITRA)

Deficiency of the interleukin-36 receptor antagonist (DITRA) is an autosomal recessive disease caused by mutations of IL36RN gene.1 Patients suffer from flares of acute generalised pustular psoriasis and systemic inflammation. We present two paediatric cases of DITRA with a severe clinical course, resistant to multiple therapies in whom the use of high doses of ustekinumab (a monoclonal antibody against the p40 subunit of both IL-12 and IL-23) lead to a persistent control of the disease. A 4-year-old boy, born from unrelated parents, presented at the age of 3 years with inverse psoriasis in the genital area. After some months, he developed diffuse pustular lesions associated with fever, elevation of acute phase reactants and poor general condition, requiring parenteral antibiotics and high-dose steroids (figure 1). Compound heterozygosity for the IL36RN P76L/S113L mutations was detected. Different treatments (acitretin, high-dose ciclosporin, …

E-learning enables parents to assess an infantile hemangioma

BACKGROUND Infantile hemangiomas (IH) at risk for complications need to be recognized early. OBJECTIVE We sought to determine if parents are able to assess, after e-learning, whether their child has an IH, is at risk for complications, and needs to be seen (urgently) by a specialist. METHODS This was a prospective study of 158 parents participating in an IH e-learning module. Parents were asked to assess their childs skin abnormality. A dermatologist answered the same questions (by e-consult). The 2 assessments were compared. RESULTS Parents showed a 96% concordance with the dermatologist for correct diagnosis after e-learning. Concordances were 79%, 75%, and 84% (P < .001), respectively, on assessing the risk of complications, the need to be seen by a specialist, and the urgency for specialized care. LIMITATIONS Parents had a relatively high education level and were therefore not representative of the general population. CONCLUSION Parents were able to correctly diagnose and evaluate an IH after completing an e-learning module. E-learning by parents could result in earlier presentation and treatment of high-risk IH.

Risk of Non-melanoma Skin Cancer in Patients with Atopic Dermatitis Treated with Oral Immunosuppressive Drugs

There is uncertainty about the risk of developing non-melanoma skin cancer (NMSC), including basal cell carcinoma and squamous cell carcinoma (SCC), in patients with atopic dermatitis (AD) treated with oral immunosuppressive drugs. A total of 557 patients with AD treated with these drugs in the University Medical Center Utrecht and Groningen, the Netherlands, were analysed. NMSC after oral immunosuppressive treatment was reported in 18 patients (3.2%). The standardized incidence ratio for developing SCC was 13.1 (95% confidence interval (95% CI) 6.5-19.7). Patients developing NMSC were older at the start of therapy (p<0.001) and data lock (p<0.001) compared with patients without NMSC. No significant differences were found in sex, cumulative days of oral immunosuppressive drugs and follow-up between these groups (p=0.42, p=0.88, and p=0.34, respectively). In interpreting these results it is important to include other factors, such as lack of association between treatment duration and tumour development and the long interval between treatment discontinuation and tumour development in some patients.

Hemangiomen: wanneer en hoe te behandelen

SamenvattingTotté JEE, Breugem CC, De Graaf M, Toonstra J, Raphaël MF, Breur-Raymakers GJLM, Speleman L, Breur JMPJ, Pasmans SGMA. Hemangiomen: wanneer en hoe te behandelen. Huisarts Wet 2013;56(2):74-8.De meeste hemangiomen op de kinderleeftijd hebben een gunstig beloop. Op basis van zorgvuldige anamnese en lichamelijk onderzoek kan de huisarts niet alleen een hemangioom van een vasculaire malformatie onderscheiden, maar ook een inschatting maken van een eventueel verhoogde kans op een gecompliceerd beloop. Bètablokkers zijn effectief gebleken bij hemangiomen en hebben een gunstig bijwerkingenprofiel. Behandeling in een vroeg stadium kan complicaties en zelfs levensbedreigende situaties voorkomen. Vroege doorverwijzing is daarom belangrijk. Dit artikel presenteert aandachtspunten om risicovolle hemangiomen snel te kunnen herkennen.De goede ervaringen met bètablokkers hebben ertoe geleid dat de behandeling, die tot nog toe was voorbehouden aan expertisecentra, voor een deel kan worden overgedragen aan de tweede, en op termijn ook aan de eerste lijn. Een belangrijke rol daarbij speelt het KinderHuidhuis, een digitaal platform voor specialist, huisarts, verzorger en patiënt dat onder andere voorziet in de coaching van de behandelend arts vanuit het expertisecentrum.Totté JEE, Breugem CC, De Graaf M, Toonstra J, Raphaël MF, Breur-Raymakers GJLM, Speleman L, Breur JMPJ, Pasmans SGMA. When and how should haemangioma be treated? Huisarts Wet 2013;56(2):74-8.Most haemangiomas of infancy have a favourable course. With a careful history and physical examination, the general practitioner not only can distinguish between a haemangioma and vascular malformations, but also assess the potentially increased risk of complications. Haemangiomas can be treated effectively with beta-blockers such as propranolol in specialized centres, and a proactive policy is essential to prevent later damage or even life-threatening situations. Early referral is increasingly important. This articles present guidelines on how to recognize potentially dangerous haemangiomas. The beneficial effect of beta-blockers has resulted in doctors in primary and secondary care being involved in the treatment and follow-up of patients with haemangiomas. ‘KinderHuidhuis’, the Dutch digital platform for specialists, general practitioners, care providers, and patients interested in infant skin problems provides expertise and coaching for doctors involved in the treatment of these patients.

Juvenile interleukin-36 receptor antagonist deficiency (DITRA) with c.80T>C (p.Leu27Pro) mutation successfully treated with etanercept and acitretin

DITRA: deficiency of interleukin-36 receptor antagonist GPP: generalized pustular psoriasis IL36RN: interleukin-36 receptor gene OMIM: online Mendelian inheritance in man PASI: psoriasis activity and severity index INTRODUCTION General pustular psoriasis (GPP) is a rare form of psoriasis and is clinically characterized by widespread eruptions of sterile pustules and bright erythematous skin accompanied by periods of fever, chills, rigors, neutrophilia, and elevated serum Creactive protein. Acrodermatitis of Hallopeau, palmoplantar psoriasis pustulosis, and annular pustular psoriasis may be variations of this GPP. In 2011, Marrakchi et al reported a subgroup of GPP patients with a specific genetic defect: a deficiency of interleukin-36 receptor antagonist (DITRA). We report a case of juvenile DITRA successfully treated with acitretin in combination with etanercept.