Severe atopic dermatitis in early infancy: characteristics, challenges and new perspectives in clinical practice

Atopic dermatitis (AD) is the most common skin disease in infants and children with a prevalence of 10% in the first two years of life. In this age group up to 15% are severely affected. “Children are not little adults” - this applies in particular to infants with severe atopic dermatitis. Age-specific clinical aspects (psychosocial, neurocognitive, morphological) of the disease require an adjusted disease management. Considering recent approval of systemic treatment options, early identification of infants and children with severe and early persistent disease is of particular importance also in view of possible prevention of atopic comorbidity. As several inborn errors of immunity (IEI) share features of the atopic phenotype, it is essential for clinicians to distinguish signs of immunodeficiency from severe AD. Here, we describe a practical approach on the basis of clinical history and key dermatological and laboratory findings. Furthermore, this paper is aimed at providing an update on general management of severe AD in early infancy, including recommendations for systemic treatment

Toll-Like Receptor Expression in Human Keratinocytes: Nuclear Factor κB Controlled Gene Activation by Staphylococcus aureus is Toll-Like Receptor 2 But Not Toll-Like Receptor 4 or Platelet Activating Factor Receptor Dependent

Cultured primary human keratinocytes were screened for their expression of various members of the toll-like receptor (TLR) family. Keratinocytes were found to constitutively express TLR1, TLR2, TLR3, TLR5, and TLR9 but not TLR4, TLR6, TLR7, TLR8, or TLR10 as shown by polymerase chain reaction analysis. The expression of the crucial receptor for signaling of staphylococcal compounds TLR2 was also confirmed by immunohistochemistry, in contrast to TLR4, which showed a negative staining pattern. Next, we analyzed the activation of the proinflammatory nuclear transcription factor κB by Staphylococcus aureus strain 8325-4. Using nuclear extract gel shifts, RelA staining, and luciferase reporter transfection plasmids we found a clear induction of nuclear factor κB translocation by the bacteria. This translocation induced the transcription of nuclear factor κB controlled genes such as inducible nitric oxide synthetase, COX2, and interleukin-8. Transcription of these genes was followed by production of increased amounts of interleukin-8 protein and NO. Inhibition experiments using monoclonal antibodies and the specific platelet activating factor receptor inhibitor CV3988 showed that nuclear factor κB activation by S. aureus was TLR2 but not TLR4 or platelet activating factor receptor dependent. In line, the purified staphylococcal cell wall components lipoteichoic acid and peptidoglycan, known to signal through TLR2, also showed nuclear factor κB translocation in human keratinocytes, indicating a crucial role of the staphylococcal cell wall in the innate immune stimulation of human keratinocytes. These results help to explain the complex activation of human keratinocytes by S. aureus and its cell wall components in various inflammatory disorders of the skin

Topical Steroids under Wet-Wrap Dressings in Atopic Dermatitis -- A Vehicle-Controlled Trial

Background: The wet-wrap dressing technique has proved to be beneficial in cases of exacerbated atopic dermatitis (AD) skin lesions. Objective: The effect of wet-wrap dressings was investigated in a controlled trial comparing a steroid (mometasone furoate 0.1%)-containing and a steroid-free (vehicle) preparation in an in-patient comparison study. Methods: 20 children aged 2–17 years with exacerbated AD were treated twice daily with wet-wrap dressings over a 5-day period. Results: AD in treated areas significantly improved in both study arms; however, the effect was significantly better in the mometasone-treated group (p < 0.01). Transepidermal water loss improved in both arms without any significant differences. Staphylococcus aureus colonization decreased during the first 3 days of active treatment independently of the therapeutic modalities chosen. At day 5, colony counts further dropped on the steroid-treated lesions. Conclusion: Application of the wet-wrap dressing technique for exacerbated AD lesions is effective, combination with a topical steroid being superior to a steroid-free application without bearing the risk of a bacterial superinfection

Entwicklung eines Gesamtkonzeptes zur Vorsorge und Versorgung von Patienten mit atopischem Ekzem

Ziel der vorliegenden Arbeit war es, die Versorgung von Patienten mit atopischem Ekzem (AE) zu verbessern. Dazu wurden im Bereich Diagnostik TARC/CCL17 (thymus and activation regulated chemokine) als neuer Parameter zur Quantifizierung des Schweregrads evaluiert. Untersuchungen zur pathogenetischen Bedeutung verschiedener mikrobieller Faktoren, insbesondere der Staphylokokken-Superantigene, ergänzen diesen Teil. Zur gezielten Verbesserung der Therapie von Patienten mit AE wurde die Effektivität der Basistherapie, die Technik der fett-feuchten Verbände in Kombination mit topischen Glukokortikosteroiden sowie die Wirksamkeit des Kalzineurininhibors Tacrolimus im Vergleich mit einem modernen Standardglukokortikoid untersucht. Im Bereich neuer Therapiekonzepte haben wir Wirkmechanismen der UVA1-Therapie analysiert, die klinische Wirksamkeit von Probiotika in der Therapie des kindlichen AE evaluiert und den anti-IgE-Antikörper Omalizumab als neue Therapieoption für das schwere AE erstmals in einer Serie klinisch und immunologisch untersucht. Einen besonderen Schwerpunkt meiner Arbeit stellte die Erarbeitung eines ambulanten Schulungsprogramms für Kinder mit atopischem Ekzem und deren Eltern sowie die Etablierung der Neurodermitisakademie München-Alpenraum zur Ausbildung von Neurodermitistrainern dar