Rothmund-Thomson syndrome and osteoma cutis in a patient previously diagnosed as COPS syndrome.

We present a patient with poikiloderma, severe osteoporosis and a mild intellectual disability. At the age of 9 years, this patient was proposed to suffer from a novel disease entity designated as calcinosis cutis, osteoma cutis, poikiloderma and skeletal abnormalities (COPS) syndrome. At the age of 35, he was diagnosed with Hodgkin's lymphoma. Recently, biallelic pathogenic variants in the RECQL4 gene were detected (c.1048_1049delAG and c.1391-1G>A), confirming a diagnosis of Rothmund-Thomson syndrome (RTS). In the brother of this patient, who had a milder phenotype, a similar diagnosis was made. CONCLUSION: We conclude that COPS syndrome never existed as a separate syndrome entity. Instead, osteoma cutis may be regarded as a novel feature of RTS, whereas mild intellectual disability and lymphoma may be underreported parts of the phenotype. What is new: • Osteoma cutis was not a known feature in Rothmund-Thomson patients. • Intellectual disability may be considered a rare feature in RTS; more study is needed. What is known: • RTS is a well-described syndrome caused by mutations in the RECQL4 gene. • Patients with RTS frequently show chromosomal abnormalities like, e.g. mosaic trisomy 8.

Quality of life measurement in atopic dermatitis. Position paper of the European Academy of Dermatology and Venereology (EADV) Task Force on quality of life.

There is a need for researchers to have easy reference to the wide spectrum of different types of quality of life (QoL) instruments that can be used in atopic dermatitis (AD). Previous reviews on QoL in AD do not cover the full spectrum of QoL measures used in studies on AD. This study, on behalf of the European Academy of Dermatology and Venereology (EADV) Task Force on QoL, contains information on instruments available for health-related QoL and family QoL assessment in AD including information on validation, experience of QoL assessment in AD for different purposes, peculiarities of QoL assessment in different age groups, expert analysis of available instruments including data on limitations of their use and recommendations of the Task Force.

ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients.

Atopic dermatitis (AD) is a clinically defined, highly pruritic, chronic inflammatory skin disease of children and adults. The diagnosis is made using evaluated clinical criteria. Disease activity is best measured with a composite score assessing both objective signs and subjective symptoms, such as SCORAD. The management of AD must consider the clinical and pathogenic variabilities of the disease and also target flare prevention. Basic therapy includes hydrating topical treatment, as well as avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment of visible skin lesions is based on topical glucocorticosteroids and the topical calcineurin inhibitors tacrolimus and pimecrolimus. Topical calcineurin inhibitors are preferred in sensitive locations. Tacrolimus and mid-potent steroids are proven for proactive therapy, which is long-term intermittent anti-inflammatory therapy of the frequently relapsing skin areas. Systemic anti-inflammatory or immunosuppressive treatment is indicated for severe refractory cases. Biologicals targeting key mechanisms of the atopic immune response are promising emerging treatment options. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R-blockers) may diminish pruritus, but do not have sufficient effect on lesions. Adjuvant therapy includes UV irradiation, preferably UVA1 or narrow-band UVB 311 nm. Dietary recommendations should be patient specific and elimination diets should only be advised in case of proven food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress-induced exacerbations. 'Eczema school' educational programmes have been proven to be helpful for children and adults.

Propranolol in the treatment of infantile haemangiomas: lessons from the European Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce survey.

BACKGROUND: Oral propranolol is widely prescribed as first-line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres. OBJECTIVES: The Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce was founded to establish patterns of use of propranolol in IHs. METHODS: Participating centres entered data on all of their patients who had completed treatment with oral propranolol for IHs, using an online data capture tool. RESULTS: The study cohort comprised 1097 children from 39 centres in eight European countries. 76·1% were female and 92·8% had a focal IH, with the remainder showing a segmental, multifocal or indeterminate pattern. The main indications for treatment were periocular location (29·3%), risk of cosmetic disfigurement (21·1%) and ulceration and bleeding (20·6%). In total 69·2% of patients were titrated up to a maintenance regimen, which consisted of 2 mg kg(-1) per day (85·8%) in the majority of cases. 91·4% of patients had an excellent or good response to treatment. Rebound growth occurred in 14·1% upon stopping, of whom 53·9% were restarted and treatment response was recaptured in 91·6% of cases. While there was no significant difference in the treatment response, comparing a daily maintenance dose of < 2 mg kg(-1) vs. 2 mg kg(-1) vs. > 2 mg kg(-1) , the risk of adverse events was significantly higher: odds ratio (OR) 1 vs. adjusted OR 0·70, 95% confidence interval (CI) 0·33-1·50, P = 0·36 vs. OR 2·38, 95% CI 1·04-5·46, P = 0·04, Ptrend < 0·001. CONCLUSIONS: The PITCH survey summarizes the use of oral propranolol across 39 European centres, in a variety of IH phases, and could be used to inform treatment guidelines and the design of an interventional study.

Support for the hypoxia theory in the pathogenesis of infantile haemangioma.

BACKGROUND: The pathogenesis of infantile haemangioma (IH) is unknown. Several mechanisms have been proposed, including hypoxia, which triggers upregulation and stabilization of hypoxia-inducible factor (HIF)1α. HIF1α stimulates downstream transcription of target genes that enhance angiogenesis. AIM: To identify possible involvement of hypoxia in the pathogenesis of IH, as hypoxia signalling constitutes a potential therapeutic target. METHODS: IH tissue samples collected during the period 1991-2011 (preserved in paraffin wax) were immunohistochemically analysed for HIF1α and the known HIF1α targets: BCL2/adenovirus E1B kD-interacting protein family member 3 (BNIP3), carbon anhydrase (CA)-IX, glucose transporter (GLUT)-1, phosphorylated protein kinase B (pAKT), phosphorylated S6 protein (pS6) and vascular endothelial growth factor (VEGF). Four observers independently assessed the findings. RESULTS: Of the 10 IH samples, 2 appeared to be in the growth phase. In all samples, GLUT-1, BNIP3, pAKT and VEGF were positive, CA-IX was weakly positive, and HIF1α was negative. pS6 was positive in 9/10 cases and negative in 1/10. CONCLUSIONS: Several factors implicated in hypoxia-induced angiogenesis may be involved in IH development. However, the small sample size and retrospective approach of the study preclude definitive conclusions. Prospective studies are needed to conclusively determine which of the factors involved in the (hypoxia) cascade are required for an IH to grow, and could thus be a possible target of drugs for IH treatment.

Intractable vascular autonomic dysregulation (Harlequin phenomenon) in two brothers: another indication for propranolol?

Vascular autonomic dysregulation, in the most extreme presentation known as Harlequin phenomenon, is a rare condition. It manifests as a sudden and brief paroxystic change in skin color, resulting in two different colors on the body. It is supposed that this condition occurs due to a vasomotor instability. This again is caused by sympathetic disautonomy, which is a consequence of hypothalamic peripheral vascular tone control immaturity in the newborn. Typically, there is spontaneous regression. We describe two brothers who both had this condition in their first life years. Clinical symptoms included frequent attacks of discoloration of extremities (up to four times per day) accompanied with terrifying crying fits, interpreted by the parents as pain. These patients were treated with propranolol, a nonselective beta-blocker, resulting in improvement of symptoms: only occasional attacks were seen. Beta-blockers act on ß1 -adrenoceptors in the heart, thereby preventing the positive chronotropic and inotropic effects mediated by these receptors. We hypothesize that propranolol, which is very lipophilic and therefore also acts on ß-receptors of the central nervous system, acts on the sympathetic system.

The European TREatment of severe Atopic eczema in children Taskforce (TREAT) survey.

BACKGROUND: There is a paucity of evidence for the use of systemic agents in children with atopic eczema refractory to conventional therapy, resulting in considerable variation in patient management. OBJECTIVES: The European TREatment of severe Atopic eczema in children Taskforce (TREAT) survey was established to collect data on current prescribing practice, to identify factors influencing the use of specific systemic agents, and to inform the design of a clinically relevant intervention study. METHODS: Consultant physician members of the paediatric dermatology societies and interest groups of eight European countries were invited to participate in a web-based survey. The multiple-response format questionnaire collated data on clinical practice in general, as well as detailed information on the use of systemic agents in refractory paediatric atopic eczema. RESULTS: In total, 343/765 members (44·8%) responded to the invitational emails; 89·2% were dermatologists and 71% initiate systemic immunosuppression for children with severe atopic eczema. The first-line drugs of choice were ciclosporin (43·0%), oral corticosteroids (30·7%) and azathioprine (21·7%). Ciclosporin was also the most commonly used second-line medication (33·6%), with methotrexate ranked as most popular third choice (26·2%). Around half of the respondents (53·7%) replied that they routinely test and treat reservoirs of cutaneous infection prior to starting systemic treatment. Across the eight countries, penicillins were the first-line antibiotic of choice (78·3%). CONCLUSIONS: In the absence of a clear evidence base, the European TREAT survey confirms the wide variation in prescribing practice of systemic immunosuppression in refractory paediatric atopic eczema. The results will be used to inform the design of a randomized controlled trial relevant to patient management across Europe.

Guidelines for treatment of atopic eczema (atopic dermatitis) Part II.

The existing evidence for treatment of atopic eczema (atopic dermatitis, AE) is evaluated using the national standard Appraisal of Guidelines Research and Evaluation. The consensus process consisted of a nominal group process and a DELPHI procedure. Management of AE must consider the individual symptomatic variability of the disease. Basic therapy is focused on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment based on topical glucocorticosteroids and topical calcineurin inhibitors (TCI) is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the TCI tacrolimus and pimecrolimus are preferred in certain locations. Systemic immune-suppressive treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial treatment. Adjuvant therapy includes UV irradiation preferably with UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Stress-induced exacerbations may make psychosomatic counselling recommendable. 'Eczema school' educational programs have been proven to be helpful. Pruritus is targeted with the majority of the recommended therapies, but some patients need additional antipruritic therapies.

Guidelines for treatment of atopic eczema (atopic dermatitis) part I.

The existing evidence for treatment of atopic eczema (atopic dermatitis, AE) is evaluated using the national standard Appraisal of Guidelines Research and Evaluation. The consensus process consisted of a nominal group process and a DELPHI procedure. Management of AE must consider the individual symptomatic variability of the disease. Basic therapy is focused on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment based on topical glucocorticosteroids and topical calcineurin inhibitors (TCI) is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the TCI tacrolimus and pimecrolimus are preferred in certain locations. Systemic immune-suppressive treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial treatment. Adjuvant therapy includes UV irradiation preferably with UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Stress-induced exacerbations may make psychosomatic counselling recommendable. 'Eczema school' educational programs have been proven to be helpful. Pruritus is targeted with the majority of the recommended therapies, but some patients need additional antipruritic therapies.

Treatment of small superficial haemangioma with timolol 0.5% ophthalmic solution: a series of 20 cases.

BACKGROUND: Haemangioma of infancy (HOI) on the face may be disfiguring and alarming for parents. Usually they are not treated when they are small. Treatment of HOI with propranolol is a breakthrough. Timolol (topical treatment) and propranolol are closely related. METHODS: We considered topical treatment with timolol 0.5% ophthalmic solution 3-4 times daily in patients with small HOI. Twenty patients with small mostly superficial HOI were included. RESULTS: A series of 20 patients with HOI treated with timolol 0.5% ophthalmic solution are described. The treatment was effective in all superficial HOIs after 1-4 months. A quick direct inhibitory effect on the growth of the HOI followed by slower regression was observed. The children had to be treated during the whole proliferative phase. Deep HOIs on the nose (2 cases) and lower eyelid (1 case) showed no response. CONCLUSION: Topical timolol 0.5% ophthalmic solution is effective in HOI. Safety and effectiveness of drugs like topical timolol and topical propranolol require further investigation but they seem very safe when used in small HOIs. We recommend that small superficial HOIs should be treated in an early proliferative phase.

Haemangioma of infancy: two case reports with an overdose of propranolol.

An 8-week-old infant was treated with oral propranolol for a haemangioma of infancy. The standard dose (according to protocol) is 2 mg/kg/day but, because of a mistake by the pharmacist, the child was treated with 8 mg/kg/day without any side effects (pulse, blood pressure and glucose stayed normal).

Scoring the proliferative activity of haemangioma of infancy: the Haemangioma Activity Score (HAS).

BACKGROUND: Haemangioma of infancy (HOI) is the most frequently occurring benign tumour of infancy. A good, reliable and objective scoring system for haemangioma activity is not yet available. AIM: We have developed a simple system called the Haemangioma Activity Score (HAS) for scoring the (disease) proliferative activity of haemangiomas. The current study was undertaken to validate this system. METHODS: We validated the HAS in a comparative study of photographs taken during consultations from 2000 until 2008 (n = 78). Agreement between three observers was assessed at two different time points (t(0) and t(1)) with a minimum interval of 6 months between them, using interclass correlation coefficients (ICC). RESULTS: Agreement between observers was good. The average ICC of the HAS at t(0) and t(1) was 0.72 and 0.76, respectively. The average ICC of the HAS for the changes from baseline (HAS at t(0) minus HAS at t(1) ) was 0.69. CONCLUSIONS: We conclude that the HAS is a good system for scoring the proliferative activity of haemangiomas, and believe it to be useful in future investigations. The number of studies comparing different therapies for treating haemangiomas is steadily increasing, and the HAS (before and after treatment) may provide a valuable scoring system for evaluating such therapies.

Skin signs in child abuse and differential diagnosis.

Child abuse has been recognized as a serious problem, of which the awareness in medical discipline but also in the general public has been increased since many years. The reporting of child abuse has therefore been increased during the last years. Also in politics it has been noted that the current situation around child abuse is alarming and the caring approach has many short-comings in early recognition and treatment. The skin is the most accessible organ of the human being. It is also the most frequently injured organ in child abuse. Skin abnormalities are visible to everyone. Therefore you need specific skills to correctly diagnose skin findings . The diagnosis of skin abnormalities in suspected child abuse is the work of experienced and dedicated specialists, e.g. pediatric dermatologists who are able to read the skin. Diagnostic errors can be prevented through close cooperation between forensic pediatrics, pediatric dermatology and pediatric radiology, but also other specialists should be consulted in difficult problematic clinical cases. Several skin disorders may mimic child abuse. Suspicion of child abuse must be approached just like every other medical problem in a child, namely based on expertise and multi-disciplinary cooperation and always supported by second opinion. In this review article skin signs of child abuse are stressed and the most common confusing dermatological disorders are illustrated.

Patient-Oriented SCORAD (PO-SCORAD): a new self-assessment scale in atopic dermatitis validated in Europe.

BACKGROUND: Patient-oriented medicine is an emerging concept, encouraged by the World Health Organization, to greater involvement of the patient in the management of chronic diseases. The Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD) index is a self-assessment score allowing the patient to comprehensively evaluate the actual course of atopic dermatitis (AD), using subjective and objective criteria derived mainly from the SCORAD, a validated AD severity clinical assessment tool. OBJECTIVES: To validate the PO-SCORAD index in a large European population of patients exhibiting all forms of AD severity by assessing its correlation with the SCORAD index. PATIENTS/METHODS: Four hundred and seventy-one patients (185 adults, 286 children) consulting for AD in hospitals from 9 European countries were recruited. The investigators and the patients used the SCORAD and PO-SCORAD scales, respectively, to assess AD severity at inclusion (D0) and 28 ± 7 days later (D28). RESULTS: Patient-Oriented SCORing Atopic Dermatitis and SCORAD scores were significantly correlated at D0 [r = 0.67 (95% CI: 0.62; 0.72), P < 0.0001]. Consistency was confirmed at D28, with a stronger linear correlation between both scales [r = 0.79 (95% CI: 0.75; 0.83), P < 0.0001]. Absolute changes from baseline in SCORAD and PO-SCORAD scores were also significantly correlated [r= 0.71 (95% CI: 0.64; 0.76), P < 0.0001]. Although no specific intervention was investigated, AD improved over the study, with a decrease of PO-SCORAD and SCORAD scores from D0 to D28 by -19.19% and -24.39%, respectively. The consistency of the correlations was similar in the adult and children groups. CONCLUSIONS: This study validated the use of PO-SCORAD to self-assess AD severity and demonstrated its good correlation with SCORAD.

Use of skin substitute dressings in the treatment of staphylococcal scalded skin syndrome in neonates and young infants.

BACKGROUND: Staphylococcal scalded skin syndrome (SSSS) is a rare toxin-mediated skin disease caused by Staphylococcus aureus and seen in infants and children younger than 5 years. OBJECTIVES: The supportive role of skin substitutes in SSSS is stressed as a new and relatively unknown method. METHODS: Retrospective observational case-series study, in neonates and young infants diagnosed with SSSS. RESULTS: Seven infants with SSSS, treatment with antibiotics, skin substitutes, strict pain relief strategy and prognosis were described. One of them was severely affected and deceased. CONCLUSION: This study describes 7 infants with SSSS and stresses the important role of skin substitutes as Omiderm® and Suprathel® as valuable adjuvant treatment modality.

Management of urticaria and angioedema in children: new trends.

Urticaria in childhood is a common problem. History of development of urticaria should be carefully taken from a written history/information list. For urticaria, the EAACI/GALEN/EDF consensus guidelines on definition, classification, diagnosis and management of urticaria should be considered. Soon an updated version of a new consensus will appear. The new classification of urticaria includes 3 main groups: spontaneous or idiopathic urticaria (divided in acute <6 weeks and chronic urticaria ≥6 weeks), physical urticaria (cold contact urticaria, delayed pressure urticaria) and other urticaria disorders such as aquagenic urticaria. In general aspects, there is no difference between children and adults, except some details. In children most urticaria are acute idiopathic or physical of character. Also, urticarial flares in atopic dermatitis in young children are common as manifestation of food allergy First step of treatment is directed to the cause (that is difficult in chronic urticaria) and triggering factors. The currently recommended first line treatment is application of oral nonsedating H1 antihistamines. If needed, the dosage of antihistamines should be up to two-fold (in adults four-fold), although evidence is lacking for this, whereas alternative treatment should be reserved as add-on therapy for unresponsive patients.

ETFAD/EADV eczema task force 2009 position paper on diagnosis and treatment of atopic dermatitis.

BACKGROUND: The diagnosis of atopic dermatitis (AD) is made using evaluated clinical criteria. Management of AD must consider the symptomatic variability of the disease. METHODS: EADV eczema task force developed its guideline for atopic dermatitis diagnosis and treatment based on literature review and repeated consenting group discussions. RESULTS AND DISCUSSION: Basic therapy relies on hydrating topical treatment and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment based on topical glucocorticosteroids and topical calcineurin antagonists is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the topical calcineurin inhibitors, tacrolimus and pimecrolimus are preferred in certain locations. Systemic anti-inflammatory treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial/antiseptic treatment. Systemic antihistamines (H1) can relieve pruritus, but do not have sufficient effect on eczema. Adjuvant therapy includes UV irradiation preferably of UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Stress-induced exacerbations may make psychosomatic counselling recommendable. 'Eczema school' educational programmes have been proven to be helpful.