Efficacy and safety of fumaric acid esters in young patients aged 10-17 years with moderate-to-severe plaque psoriasis: a randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Apart from biologics, no systemic drugs are approved in Europe for children with moderate-to-severe psoriasis. Retrospective observational studies have shown promising results for fumaric acid esters (FAE) in this setting. OBJECTIVES: To show superiority of FAE over placebo in terms of treatment response after 20 weeks in children and adolescents aged 10-17 years. METHODS: In a multicentre, randomized, double-blind, placebo-controlled phase IIIb study, patients aged 10-17 years with moderate-to-severe plaque psoriasis requiring systemic therapy were randomized 2 : 1 to receive FAE (n = 91) or placebo (n = 43) over 20 weeks, followed by an open-label FAE treatment phase. The coprimary endpoints were ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and Physician's Global Assessment (PGA) score of 0 or 1 (clear or almost clear) at week 20. The study was registered with EudraCT number 2012-000035-82. RESULTS: At week 20, 55% [95% confidence interval (CI) 0·44-0·65] of FAE-treated patients achieved a PASI 75 response vs. 19% (95% CI 0·08-0·33) in the placebo group (absolute difference 36%, 95% CI 0·20-0·53; P < 0·001). In total, 42% (95% CI 0·32-0·53) in the FAE group vs. 7% (95% CI 0·01-0·19) in the placebo group achieved a PGA score of 0 or 1 at week 20 (absolute difference 35%, 95% CI 0·21-0·49; P < 0·001). During the double-blind period, drug-related adverse events occurred more frequently in patients receiving FAE compared with placebo (76% vs. 47%). Gastrointestinal disorders were the most common adverse events. CONCLUSIONS: FAE administered over a period of 20 weeks demonstrated a better response than placebo; the difference was statistically significant and clinically meaningful. Application up to 40 weeks was generally well tolerated. However, further studies are required.

[Pigmented macules as possible early signs of genetic syndromes]. / Pigmentierte Flecken als mögliche Frühzeichen genetischer Syndrome.

Solitary congenital or early apparent pigmented macules are usually without relevance; however, when multiple, extensive or in a patterned arrangement, they are not uncommonly the first sign of an underlying genetic syndrome. The present article gives an overview on the clinical significance of multiple café-au-lait macules, multiple lentigines and pigmentary mosaicism and discusses the differential diagnosis of associated syndromes. Early diagnosis with the essential contribution of the dermatologist is not only important for genetic counseling but can also contribute to avoidance of sometimes life-threatening complications.

Tracing the evolution of the heterotrimeric G protein α subunit in Metazoa.

BACKGROUND: Heterotrimeric G proteins are fundamental signaling proteins composed of three subunits, Gα and a Gßγ dimer. The role of Gα as a molecular switch is critical for transmitting and amplifying intracellular signaling cascades initiated by an activated G protein Coupled Receptor (GPCR). Despite their biochemical and therapeutic importance, the study of G protein evolution has been limited to the scope of a few model organisms. Furthermore, of the five primary Gα subfamilies, the underlying gene structure of only two families has been thoroughly investigated outside of Mammalia evolution. Therefore our understanding of Gα emergence and evolution across phylogeny remains incomplete. RESULTS: We have computationally identified the presence and absence of every Gα gene (GNA-) across all major branches of Deuterostomia and evaluated the conservation of the underlying exon-intron structures across these phylogenetic groups. We provide evidence of mutually exclusive exon inclusion through alternative splicing in specific lineages. Variations of splice site conservation and isoforms were found for several paralogs which coincide with conserved, putative motifs of DNA-/RNA-binding proteins. In addition to our curated gene annotations, within Primates, we identified 15 retrotranspositions, many of which have undergone pseudogenization. Most importantly, we find numerous deviations from previous findings regarding the presence and absence of individual GNA- genes, nuanced differences in phyla-specific gene copy numbers, novel paralog duplications and subsequent intron gain and loss events. CONCLUSIONS: Our curated annotations allow us to draw more accurate inferences regarding the emergence of all Gα family members across Metazoa and to present a new, updated theory of Gα evolution. Leveraging this, our results are critical for gaining new insights into the co-evolution of the Gα subunit and its many protein binding partners, especially therapeutically relevant G protein - GPCR signaling pathways which radiated in Vertebrata evolution.

[Lichen nitidus and lichen striatus]. / Lichen nitidus und Lichen striatus.

Lichen nitidus is a rare, chronic dermatosis which occurs more often in children than in adults. It presents with tiny, monomorphous, lichenoid, mostly asymptomatic papules in regional or disseminated distribution which show a pathognomonic histological pattern. The pathogenesis is unclear; however, immunologic phenomena and genetic factors are under discussion. In rare cases, an association with other dermatoses and systemic diseases has been described. Moreover, medical treatments have been incriminated as triggers. Considering the self-limited course in mostly young patients, treatment must be thoroughly weighed. Possible therapeutic options include topical corticosteroids and calcineurin inhibitors as well as oral antihistamines, corticosteroids and narrow-band ultraviolet B phototherapy. Lichen striatus is an acquired, usually asymptomatic dermatosis occurring mostly in preschool children. The characteristic feature is the arrangement of small, flat, light red- to skin-colored papules along the lines of Blaschko. Therefore, a postzygotic mutation of epidermal progenitor cells induced to express new surface antigens by trigger factors as infections, vaccinations or trauma with consecutive immune reaction is assumed. Nail involvement of the affected limb can rarely occur. Lichen striatus usually heals without scarring within several months, so that therapies with severe side effects are obsolete. Mild topical corticosteroids or calcineurin inhibitors may be used, especially if patients exceptionally suffer from pruritus. A postinflammatory hypopigmentation can persist for months to years.

[Staphylococcal Scalded Skin Syndrome in a Very Low Birth Weight Premature Infant]. / Staphylococcal Scalded Skin Syndrome bei einem sehr unreifen Frühgeborenen.

INTRODUCTION: Staphylococcal scalded skin syndrome (SSSS) was often endemic in the past but is nowadays rare. The hematogeneous spread of exfoliative toxins A (ETA) or B (ETB) produced by specific Staphylococcus aureus strains causes a scald-like eruption with disseminated bullous lesions. CASE REPORT: A perioral impetigo lesion occurred on day 14 of life in a preterm male infant (1,065 g, 30 weeks of gestational age). Empiric antibiotic therapy with cefotaxime and vancomycin was given for 6 days and led to complete resolution. A Staphylococcus aureus strain was isolated. After a symptom-free interval a relapse was noted on day 26 of life. Despite restarting the antibiotic therapy immediately the initial lesion expanded, and disseminated flaccid blisters on an erythematous base appeared within a few hours. On histological examination the cleavage was in the level of the granular layer. There was no mucosal involvement, and the Nikolsky I sign was positive. The antibiotic therapy was changed to a combination of cefotaxime, flucloxacillin and clindamycin which rapidly stopped progression of the exfoliation. Supportive therapy included adequate analgesia, parenteral rehydration, and application of local antiseptics. The preterm infant completely recovered. In the primary lesion an ETA-producing Staphylococcus aureus strain was isolated. Nasal microtrauma by a nasogastric tube was assumed to have caused the fulminant disease. At the same time, no other Staphylococcus aureus infections were seen in our Department of Neonatology. DISCUSSION: According to the literature, the incidence of SSSS is higher in premature infants and newborns than in older children. Possible causes include lower antibody levels against exfoliative toxins and renal immaturity. Rapid diagnosis and immediate appropriate antibiotic therapy are essential to prevent secondary infection, dehydration with electrolyte disturbance, death, and endemic spread.

[Differential diagnosis of oral mucosal erosions and ulcers in children]. / Differenzialdiagnose erosiver und ulzeröser Mundschleimhauterkrankungen im Kindesalter.

BACKGROUND: Oral ulcers and erosions are of great clinical importance because they are common in childhood and adolescence and generally painful. They can be related to harmless conditions, such as recurrent aphthous stomatitis. On the other hand, they can be associated with severe systemic diseases making an early diagnosis and initiation of treatment necessary. OBJECTIVES: We herein focus on the systematic presentation of differential diagnoses of oral ulcers and erosions in pediatric patients and present clues in the history and clinical features that are helpful to establish the diagnosis. CONCLUSIONS: Patient's age at the beginning of the symptoms, differentiation between acute and chronic course, distribution of mucosal lesions, additional involvement of the skin, extracutaneous symptoms, general condition of the patient, comorbidities and medication may be determining factors of the correct diagnosis. In children and adolescents aphthous stomatitis, infections and trauma are the most frequent causes of oral ulcerations or erosions of the mucous membranes.