Digital ultraviolet therapy: a novel therapeutic approach for the targeted treatment of psoriasis vulgaris.

BACKGROUND: 8-Methoxypsoralen-UVA (PUVA) and narrowband ultraviolet B (NB-UVB) are well-established treatments for chronic plaque-type psoriasis vulgaris. However, long-term risks of PUVA therapy include premature skin ageing and squamous cell carcinoma. OBJECTIVES: To develop a device for targeted UV therapy of psoriatic plaques with protection of the healthy adjacent skin to reduce the risk for premature skin ageing and squamous cell carcinoma. METHODS: In total 28 patients with exacerbated psoriasis vulgaris were treated with the digital phototherapy device skintrek(®) [cream PUVA (n = 8), bath PUVA (n = 11) and UVB (n = 9)] or with conventional bath PUVA (n = 9) or NB-UVB (n = 4). RESULTS: The local Psoriasis Area and Severity Index (PASI) score was significantly reduced from a mean of 6·25 at baseline to 2·75 at the end of therapy in the skintrek cream PUVA group, from 6·4 to 3·0 in the skintrek bath PUVA group and from 5·5 to 2·0 in the skintrek UVB group. Treatment with skintrek cream PUVA reduced the mean local PASI by 54%, while skintrek bath PUVA did so by 51% and skintrek UVB by 63%. Targeted skintrek PUVA and skintrek UVB of inflamed psoriatic skin avoided skin pigmentation and were not inferior to conventional bath PUVA and NB-UVB therapy regimens. CONCLUSIONS: Targeted UV therapy of psoriatic plaques with the digital phototherapy device skintrek is as effective as conventional cream and bath PUVA, as well as NB-UVB, while simultaneously sparing the healthy adjacent skin. It therefore potentially reduces the carcinogenic risk, reduces premature skin ageing and avoids tanning of healthy surrounding skin.

Impaired NLRP3 inflammasome expression and function in atopic dermatitis due to Th2 milieu.

BACKGROUND: Atopic dermatitis (AD) and psoriasis patients are frequently colonized with Staphylococcus aureus (S. aureus) that produce the staphylococcal exotoxin α-toxin. However, only patients with AD suffer from bacterial superinfections with this pathogen, which implicates immunological differences in AD vs psoriasis in combating these bacteria. S. aureus recognition is partially mediated by intracellular nucleotide-binding oligomerization domain receptors (NLRs), which link α-toxin to caspase-1 activation through the formation of the NLRP3 inflammasome and to IL-1ß secretion. OBJECTIVE: To investigate (i) NLRP3 expression in the context of different T-helper cytokine milieus and (ii) its function in response to sublytic α-toxin stimulation in patients with AD and psoriasis compared with healthy controls. METHODS: NLRP3 expression and function were investigated in lesional AD and psoriasis skin as well as in primary keratinocytes (HPKs) and monocytes upon stimulation with Th1, Th2, Th17 and Th22 cytokines or staphylococcal α-toxin, respectively, at the mRNA and protein (ELISA, immunohistochemistry and immunofluorescence) level. RESULTS: NLRP3 and caspase-1 expressions were reduced in lesional AD skin compared to psoriatic and healthy skin. IL-4, IL-5 and IL-13 downregulated NLRP3 and ASC, whereas interferon-γ upregulated NLRP3 in HPKs. In monocytes, caspase-1 expression was reduced by Th2 cytokines and enhanced by a Th1 milieu. Caspase-1-dependent IL-1ß secretion was impaired in monocytes from patients with AD compared to patients with psoriasis and healthy controls by α-toxin stimulation following priming with lipoteichoic acid. CONCLUSION: Impaired NLRP3 expression and function may partially explain how skin colonization and infection with S. aureus can contribute to chronic skin inflammation in AD.

Interleukin (IL)-31 activates signal transducer and activator of transcription (STAT)-1, STAT-5 and extracellular signal-regulated kinase 1/2 and down-regulates IL-12p40 production in activated human macrophages.

BACKGROUND: Interleukin-31 is a cytokine expressed by activated T cells. A major function of IL-31 in atopic dermatitis (AD) is the induction of pruritus in the skin. We recently showed that IL-31 induces pro-inflammatory cytokines following staphylococcal exotoxins' stimulation in human macrophages. However, signalling pathways of IL-31 in activated human macrophages still remain unclear. The aim of the study was to investigate the signalling pathways of IL-31 receptor as well as functional effects of IL-31 in activated macrophages. METHODS: Human macrophages were prestimulated with staphylococcal exotoxins (SEB, α-toxin) to up-regulate the IL-31 receptor with and without IL-31. Phospho-signal transducer and activator of transcription (pSTAT) 1/3/5, phospho-extracellular signal-regulated kinase (ERK 1/2), ß-actin as well as p21/WAF/Cip1 levels were determined by means of Western blot analysis. Interleukin-12p40, IL-12p70 and IL-23 secretions were assessed by using an enzyme-linked immunosorbent assay. RESULTS: Interleukin-31 strongly activated STAT-1 and 5 but not STAT-3 in human macrophages after up-regulation of IL-31 receptor with staphylococcal exotoxins. p21/WAF/Cip1 expression was induced by IL-31 in activated human macrophages. Furthermore, IL-31 down-regulated. IL-12p40 secretion via ERK 1/2 phosphorylation in human macrophages following up-regulation of IL-31 receptor with staphylococcal exotoxins. CONCLUSIONS: The T helper (Th) 2 cytokine IL-31 induces pro-inflammatory effects in activated human macrophages via STAT-1 and 5 phosphorylation. Interleukin-31-induced ERK 1/2 activation contributes to the underlying mechanism of Th1 cytokine IL-12 suppression in macrophages. This mechanism may be relevant in Th2 inflammatory responses and may help to develop therapeutic strategies in IL-31-associated diseases such as AD.

Macrophages from patients with atopic dermatitis show a reduced CXCL10 expression in response to staphylococcal α-toxin.

BACKGROUND: Patients with atopic dermatitis (AD) are frequently colonized with Staphylococcus aureus (S. aureus), one-third of them producing α-toxin, which is correlated with the severity of eczema in AD. Staphylococcus aureus colonizes in patients with psoriasis as well. Distinct expression of chemokine (C-C motif) ligand (CCL) and chemokine (C-X-C motif) ligand (CXCL) chemokines has been documented in both diseases. In this study, we investigated the effects of sublytic α-toxin concentrations on human macrophages that accumulate in the skin of patients with AD and psoriasis. METHODS: IFN-γ-induced protein of 10-kDa (IP-10)/CXCL10 and macrophage-derived chemokine (MDC)/CCL22 production were evaluated at the mRNA or at the protein level using qRT-PCR or ELISA, respectively. Cell surface markers' expression and chemotaxis were determined by flow cytometry and Boyden chamber technique, respectively. RESULTS: Sublytic concentrations of α-toxin strongly induced CXCL10 in macrophages at both the mRNA and the protein levels and significantly up-regulated MHC class II expression. Supernatants of α-toxin-stimulated macrophages induced the migration of human CD4+ lymphocytes via the CXCL10 receptor (CXCR3). Macrophages from patients with AD produced lower levels of CXCL10 compared to cells from patients with psoriasis as well as healthy controls in response to α-toxin. α-Toxin did not lead to a large variation in CCL22 production in macrophages from all three groups. CONCLUSIONS: Staphylococcal α-toxin contributes to Th1 polarization by induction of CXCL10 in macrophages. Macrophages from patients with AD and psoriasis responded to α-toxin in the induction of Th1-related chemokine CXCL10 diversely, which could favour the recruitment of distinct leucocyte subsets into the skin.

The inhomogeneous structure of water at ambient conditions.

Small-angle X-ray scattering (SAXS) is used to demonstrate the presence of density fluctuations in ambient water on a physical length-scale of approximately 1 nm; this is retained with decreasing temperature while the magnitude is enhanced. In contrast, the magnitude of fluctuations in a normal liquid, such as CCl(4), exhibits no enhancement with decreasing temperature, as is also the case for water from molecular dynamics simulations under ambient conditions. Based on X-ray emission spectroscopy and X-ray Raman scattering data we propose that the density difference contrast in SAXS is due to fluctuations between tetrahedral-like and hydrogen-bond distorted structures related to, respectively, low and high density water. We combine our experimental observations to propose a model of water as a temperature-dependent, fluctuating equilibrium between the two types of local structures driven by incommensurate requirements for minimizing enthalpy (strong near-tetrahedral hydrogen-bonds) and maximizing entropy (nondirectional H-bonds and disorder). The present results provide experimental evidence that the extreme differences anticipated in the hydrogen-bonding environment in the deeply supercooled regime surprisingly remain in bulk water even at conditions ranging from ambient up to close to the boiling point.

Following excited-state chemical shifts in molecular ultrafast x-ray photoelectron spectroscopy.

The conversion of photon energy into other energetic forms in molecules is accompanied by charge moving on ultrafast timescales. We directly observe the charge motion at a specific site in an electronically excited molecule using time-resolved x-ray photoelectron spectroscopy (TR-XPS). We extend the concept of static chemical shift from conventional XPS by the excited-state chemical shift (ESCS), which is connected to the charge in the framework of a potential model. This allows us to invert TR-XPS spectra to the dynamic charge at a specific atom. We demonstrate the power of TR-XPS by using sulphur 2p-core-electron-emission probing to study the UV-excited dynamics of 2-thiouracil. The method allows us to discover that a major part of the population relaxes to the molecular ground state within 220-250 fs. In addition, a 250-fs oscillation, visible in the kinetic energy of the TR-XPS, reveals a coherent exchange of population among electronic states.

Functional effects of interleukin 31 in human primary keratinocytes.

BACKGROUND: Interleukin (IL)-31 is a T-cell cytokine acting through a heterodimeric receptor composed of IL-31RA and OSMR which is expressed on epithelial cells including keratinocytes. A major function of IL-31 in atopic dermatitis (AD) is the induction of pruritus in the skin. Inflammatory effects of IL-31 in human primary keratinocytes (HPKs) still remain unclear. We investigated expression, regulation of the IL-31 receptor as well as functions of IL-31 in HPKs. METHODS: Human primary keratinocytes were stimulated with TLR-2 ligands (Pam3Cys, lipoteichoic acid and peptidoglycan), or Th1 and Th2 associated cytokines (IFN-γ and IL-4), respectively. IL-31R expression and regulation as well as functional effects of IL-31 stimulation were then investigated at both the mRNA and protein level and compared with HPKs from patients with AD. The STAT signalling pathway and TLR-2 expression were investigated using Western blot and Immunohistochemical stainings, respectively. RESULTS: Pam3Cys or IFN-γ significantly up-regulated IL-31RA and OSMR expression. IL-31 activated STAT-3 phosphorylation in HPKs which was augmented after preactivation with Pam3Cys or IFN-γ. IL-31 enhanced the secretion of CCL2 after up-regulation of the receptor with Pam3Cys or IFN-γ. However, this was not observed in keratinocytes from AD patients where an impaired TLR-2 expression was found. CONCLUSIONS: Together, our findings show a functional role of IL-31 in HPKs and provide a new link between TLR-2 ligands and IL-31 which might be dysregulated in AD. Altered function of IL-31 may have implications for cutaneous inflammation in eczema where skin colonization with Staphylococcus aureus and dysregulation of TLR-2 have been described.

The role of T-cell reactivity towards the autoantigen α-NAC in atopic dermatitis.

BACKGROUND: A subgroup of patients with atopic dermatitis (AD) produces IgE autoantibodies to human proteins which may be present in inflamed skin and perpetuate cutaneous inflammation. OBJECTIVES: In order to investigate mechanisms of 'autoallergy' for AD we studied T-cell responses to the autoallergen Hom s 2, the human transcriptional coactivator α-nascent polypeptide-associated complex (α-NAC). METHODS: Specific proliferation of blood lymphocytes from 30 patients and 12 healthy control individuals was investigated by flow cytometry. The proliferation of skin- and blood-derived T cells was assessed in limiting-dilution assays. T-cell clones (TCC) were generated from peripheral blood and from biopsies of lesional skin of patients with AD and the phenotype and cytokine patterns were determined. RESULTS: α-NAC-specific T-cell responses were detected in patients and control individuals. α-NAC induced a significantly higher proliferation of CCR4+ (compared with CCR4-) and CLA+ (compared with CLA-) T cells from the circulation. Limiting-dilution assays revealed a high proliferation of blood and skin-infiltrating lymphocytes in the presence of α-NAC compared with control cultures. α-NAC-specific TCC generated from lesional skin of AD predominantly produced interferon-γ and some TCC also produced interleukin-17. The cytokine pattern of α-NAC TCC may contribute to keratinocyte apoptosis and eczema formation in AD. CONCLUSIONS: α-NAC-specific TCC can be generated from blood and lesional skin of patients with AD. These TCC produce not only Th2 but also Th1 cytokines which may explain the Th1 phenotype of inflammation in AD.

[Allergic contact dermatitis and atopy]. / Kontaktallergie und Atopie.

Retrospective studies demonstrate that the prevalence of skin sensitization does not significantly differ between atopic and non-atopic patients. In children and adolescents the risk for sensitization seems to occur independently from AD. According to the results of a recent study, AD patients are overrepresented in the group of polysensitized patients. IgE-mediated sensitization as well as an early onset of AD and duration of the disease have been identified as possible risk factors for skin sensitization to contact allergens. A defective permeability barrier with increased epidermal water loss is a hallmark of AD and contributes to sensitization against common allergens. A highly significant association between FLG mutations and the risk of early onset, severe, persistent AD and an increased risk for asthma has been shown in several studies. A more recent study revealed an association between FLG mutations and increased nickel sensitization, but not other contact allergens. However, further large prospective studies with well-characterized patients are necessary to clarify the correlation between impaired skin barrier, atopic dermatitis and allergic contact dermatitis.

Interleukin (IL)-31 induces pro-inflammatory cytokines in human monocytes and macrophages following stimulation with staphylococcal exotoxins.

BACKGROUND: IL-31 is a cytokine expressed by T cells following activation with cytokines or staphylococcal exotoxins. A major function of IL-31 in atopic dermatitis (AD) is the induction of pruritus in the skin via the IL-31 receptor on sensory nerve cells. However, the regulation of the IL-31 receptor and pro-inflammatory functions of IL-31 in human monocytes and monocyte-derived cells are yet to be studied in detail. OBJECTIVE: To investigate the regulation and function of IL-31 receptors in resting and activated human monocytes, macrophages and dendritic cells. METHODS: Human monocytes, macrophages and dendritic cells were stimulated with staphylococcal exotoxins (SEB, alpha-toxin) or cytokines (IFN-gamma, IL-13). IL-31RA expression and regulation were then investigated at both the mRNA and the protein level. Subsequently, functional effects of IL-31 stimulation on cytokine secretion were measured at the protein level. RESULTS: Staphylococcal exotoxins significantly up-regulated IL-31RA expression on monocytes and macrophages but not on dendritic cells at both the mRNA and the protein level. IL-31 enhanced the secretion of IL-1beta, IL-6 and IL-18 and up-regulated CD86 expression. In patients with AD, functional IL-31RA was also detected following stimulation of PBMC with IFN-gamma. However, this was not observed in healthy individuals. CONCLUSION: IL-31 induces pro-inflammatory effects in activated human monocytes and macrophages. This may have implications for cutaneous inflammation in eczema where an over-expression of IL-31 has been described previously. Moreover, our findings provide a new link between staphylococcal colonization and the worsening of inflammation via IL-31. Further therapeutic considerations may include IL-31 as a target in AD.

Impaired TLR-2 expression and TLR-2-mediated cytokine secretion in macrophages from patients with atopic dermatitis.

BACKGROUND: In many patients with atopic dermatitis (AD), the disease is complicated by their enhanced susceptibility to bacterial skin infections, especially with Staphylococcus aureus. The pattern recognition receptor toll-like receptor (TLR)-2 recognizes components of S. aureus, for example, lipoteichoic acid (LTA) and peptidoglycan (PGN) and, therefore, might be crucial in the pathogenesis and flare-ups of AD. OBJECTIVE: To investigate TLR-2 expression and cytokine secretion in macrophages from patients with AD compared to healthy controls upon TLR-2 stimulation with PGN, LTA and Pam3Cys. METHODS: Macrophages were cultivated from highly purified peripheral blood monocytes of AD patients and nonatopic healthy controls and stimulated with PGN, LTA and Pam3Cys in a time and dose-dependent manner. Afterwards, TLR-2 expression and cytokine secretion were measured on protein and mRNA level. TLR-1 and TLR-6 expression were investigated on the mRNA level. Immunohistochemical stainings from punch biopsies were performed to investigate TLR-2 expression in skin macrophages. RESULTS: We could clearly show that macrophages from patients with AD expressed significantly less TLR-2, whereas the expression pattern of TLR-1 and TLR-6 were not altered. Macrophages had a reduced capacity to produce pro-inflammatory cytokines such as IL-6, IL-8 and IL-1beta after stimulation with TLR-2 ligands. CONCLUSION: Our findings clearly show an impaired TLR-2 expression and functional differences of TLR-2-mediated effects on macrophages of AD patients compared to healthy controls which might contribute to the enhanced susceptibility to skin infections with S. aureus in AD.

[Severe hematogenous contact dermatitis after oral nickel exposition]. / Hämatogenes allergisches Kontaktekzem nach oraler Nickelexposition.

A 19-year-old woman with known strong contact sensitization to nickel sulfate presented with persistent periumbilical eczema even though she had been careful to avoid exposure to the allergen. She had childhood atopic dermatitis which had been latent but had flared a year previously, presenting as flexural eczema. Double-blind placebo-controlled oral challenge with 5 mg nickel revealed a hematogenous contact dermatitis, accompanied by fever and malaise. It resolved quickly after treatment with systemic steroids and antihistamines. The possibility of hematogenous contact dermatitis should be considered in patients with strong delayed-type hypersensitivity suffering from persistent or relapsing eczema.

[Giant keratoacanthoma in an immunocompetent patient with detection of HPV 11]. / Riesenkeratoakanthom bei einem immunkompetenten Patienten mit Nachweis von HPV 11.

A 47-year-old immunocompetent man presented with a nodule on the right side of the upper lip that appeared suddenly and grew rapidly. Histological examination was consistent with the diagnosis of keratoacanthoma which is often associated with immunosuppression. Low-risk HPV type 11 was detected in the PCR analysis. While formerly one often waited for spontaneous regression of keratoacanthomas, today one routinely treats them as a well-differentiated squamous cell carcinoma. Complete surgical excision was not possible in our patient because of the size of the tumor. Radiation with a cumulative dose of 30 Gray (15 sessions of 2 Gray) led to complete remission. In addition to ultraviolet exposure, trauma, genetic factors and chemical carcinogens, HPV should be considered as a possible cofactor in the etiology of keratoacanthoma.

Femtosecond gas-phase mega-electron-volt ultrafast electron diffraction.

The development of ultrafast gas electron diffraction with nonrelativistic electrons has enabled the determination of molecular structures with atomic spatial resolution. It has, however, been challenging to break the picosecond temporal resolution barrier and achieve the goal that has long been envisioned-making space- and-time resolved molecular movies of chemical reaction in the gas-phase. Recently, an ultrafast electron diffraction (UED) apparatus using mega-electron-volt (MeV) electrons was developed at the SLAC National Accelerator Laboratory for imaging ultrafast structural dynamics of molecules in the gas phase. The SLAC gas-phase MeV UED has achieved 65 fs root mean square temporal resolution, 0.63 Å spatial resolution, and 0.22 Å-1 reciprocal-space resolution. Such high spatial-temporal resolution has enabled the capturing of real-time molecular movies of fundamental photochemical mechanisms, such as chemical bond breaking, ring opening, and a nuclear wave packet crossing a conical intersection. In this paper, the design that enables the high spatial-temporal resolution of the SLAC gas phase MeV UED is presented. The compact design of the differential pump section of the SLAC gas phase MeV UED realized five orders-of-magnitude vacuum isolation between the electron source and gas sample chamber. The spatial resolution, temporal resolution, and long-term stability of the apparatus are systematically characterized.

Dysregulation of toll-like receptor-2 (TLR-2)-induced effects in monocytes from patients with atopic dermatitis: impact of the TLR-2 R753Q polymorphism.

BACKGROUND: Atopic dermatitis (AD) is often complicated by an enhanced susceptibility to bacterial skin infections, especially with Staphylococcus aureus. Toll-like receptors (TLR), especially TLR-2 recognizes cell wall components of S. aureus, e.g. lipoteichoic acid (LTA) and peptidoglycan (PGN). A heterozygous TLR-2 R753Q polymorphism occurs in a frequency of 11.5% in adult AD patients and has been shown to be associated with a severe phenotype of AD. METHODS: The aim of this study was to investigate the impact of TLR-2 agonists (LTA, PGN and Pam3Cys) on cytokine production in human monocytes from AD patients with the TLR-2 R753Q polymorphism compared with that of AD patients with 'wild type' TLR-2 and control individuals to elucidate the functional role of the TLR-2 R753Q polymorphism. RESULTS: Monocytes from AD patients with the TLR-2 R753Q mutation produced significantly more IL-6 and IL-12 compared with that of AD patients with nonmutated TLR-2 upon stimulation with TLR-2 agonists. CONCLUSION: We show for the first time functional differences in TLR-2 responsiveness of monocytes from AD patients with the TLR-2 R753Q mutation compared with wild type AD patients in a ligand-dependent manner. CLINICAL IMPLICATION: Our data support the emerging concept that AD patients have a dysbalance in innate and acquired immunity. TLR-2 may be essential in the pathogenesis and maintenance of AD and may be involved in the enhanced susceptibility to skin infections with S. aureus and in a higher inflammatory response in patients with AD carrying the TLR-2 polymorphism.

[Specific immunotherapy (SIT) in atopic dermatitis and food allergy]. / Spezifische Immuntherapie (SIT) bei atopischer Dermatitis und Nahrungsmittelallergie.

Atopic dermatitis (AD) is one of the most frequent chronic inflammatory skin diseases with an increasing prevalence. About 80% of adult AD patients are sensitized against seasonal or perennial aeroallergens and/or food allergens which may play a pivotal role in triggering or maintaining eczema. In addition to local and systemic therapy adjusted to the stage of the disease, the search for relevant trigger factors and then their avoidance plays a crucial role in managing AD. While the effectiveness of SIT is best established in allergic rhinitis, bronchial asthma and insect venom allergy, its use in AD is still controversial. Double-blind, placebo-controlled clinical studies are now available showing good efficacy of SIT in patients with AD. For food allergies there are clues from case reports and small clinical studies suggesting effectiveness of SIT both for food allergies and associated aeroallergens. Double-blind, placebo-controlled studies involving larger numbers of patients are needed to establish the clinical effectiveness and immunologic mechanisms of SIT in food allergies.

Encephalitis in a stone marten (Martes foina) after natural infection with highly pathogenic avian influenza virus subtype H5N1.

Recent outbreaks of disease in different avian species, caused by the highly pathogenic avian influenza virus (HPAIV), have involved infection by subtype H5N1 of the virus. This virus has also crossed species barriers and infected felines and humans. Here, we report the natural infection of a stone marten (Martes foina) from an area with numerous confirmed cases of H5N1 HPAIV infection in wild birds. Histopathological examination of tissues from this animal revealed a diffuse nonsuppurative panencephalitis with perivascular cuffing, multifocal gliosis and neuronal necrosis. Additionally, focal necrosis of pancreatic acinar cells was observed. Immunohistochemically, lesions in these organs were associated with avian influenza virus antigen in neurons, glial cells and pancreatic acinar cells. Thus, the microscopical lesions and viral antigen distribution in this stone marten differs from that recently described for cats naturally and experimentally infected with the same virus subtype. This is the first report of natural infection of a mustelid with HPAIV H5N1.

Prevalence of eardrum pathology in a cohort born in 1955.

The aim of this study was to compare the prevalence of the different types of eardrum pathology in a cohort of adults not previously treated by grommet insertion with corresponding findings obtained in a cohort previously treated with grommet insertion. A cohort born in 1955 were invited to a screening examination including otomicroscopy. In the untreated cohort, retraction of Shrapnell's membrane was found in four per cent of the ears compared to 20 per cent in the cohort treated with grommets. Tensa pathology, including atrophy and myringosclerosis, was found in six per cent of the ears in the untreated cohort and in 17 per cent in the treated cohort. Normal eardrums were found in 91 per cent of the ears. Despite the increased awareness of secretory otitis, as well as the increased rate of surgical treatment, the prevalence of eardrum pathology seems to be increasing. The reasons for this are discussed.

[Specific immunotherapy in the treatment of atopic dermatitis]. / Spezifische Immuntherapie bei der Behandlung der atopischen Dermatitis.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that is part of the atopic syndrome and is frequently associated with asthma and allergic rhinoconjunctilitis. Acute eczematous lesions are characterized by erythema, cozing and crusting, whereas chronic lesions show thickened skin and papules. In addition to local and systemic therapy adjusted to the stage of the disease, the search for relevant trigger factors and consecutively their avoidance plays a crucial role in disease management. Aeroallergens like house-dust-mites, pollen and animal epithelia represent important trigger factors in sensitized patients. While allergen-specific immunotherapy (SIT) is widely and most effective used in allergy to insect venoms and allergic rhinitis, its use in AD is still controversial. Double-blind, placebo-controlled clinical trials show that SIT is effective in patients with AD and clinically relevant sensitization to house dust mites and grass pollen and leads to clinical improvement of eczema. Despite these encouraging data, the use of SIT as a routine therapeutic approach in AD requires further evaluation.