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Andreas Wollenberg

Publications and source records attributed to Andreas Wollenberg.

At least 19 recordsLinked to original sources

Cross-sensitization between poppy seed and buckwheat in a food-allergic patient with poppy seed anaphylaxis.

The opium poppy, Papaver somniferum L., is the source of both poppy seeds and opium. The commercially available seeds are widely used as ingredients for various kinds of food. IgE-mediated sensitization to poppy seeds is rare, but, if present, clinical symptoms are usually severe. Cross-sensitizations between poppy seeds and other food allergens have been described with sesame, hazelnut, rye grain and kiwi fruit. We report the case of a 17-year-old female with an apparently food-allergic reaction after ingestion of a poppy seed cake. Allergological workup revealed a poppy seed anaphylaxis and led to the identification of a novel cross-sensitization with buckwheat.

Adolescent↗

Cathelicidin deficiency predisposes to eczema herpeticum.

BACKGROUND: The cathelicidin family of antimicrobial peptides is an integral component of the innate immune response that exhibits activity against bacterial, fungal, and viral pathogens. Eczema herpeticum (ADEH) develops in a subset of patients with atopic dermatitis (AD) because of disseminated infection with herpes simplex virus (HSV). OBJECTIVE: This study investigated the potential role of cathelicidins in host susceptibility to HSV infection. METHODS: Glycoprotein D was measured by means of real-time RT-PCR as a marker of HSV replication in skin biopsy specimens and human keratinocyte cultures. Cathelicidin expression was evaluated in skin biopsy specimens from patients with AD (n = 10) without a history of HSV skin infection and from patients with ADEH (n = 10). RESULTS: The cathelicidin peptide LL-37 (human cathelicidin) exhibited activity against HSV in an antiviral assay, with significant killing (P < .001) within the physiologic range. The importance of cathelicidins in antiviral skin host defense was confirmed by the observation of higher levels of HSV-2 replication in cathelicidin-deficient (Cnlp-/-) mouse skin (2.6 +/- 0.5 pg HSV/pg GAPDH, P < .05) compared with that seen in skin from their wild-type counterparts (0.9 +/- 0.3). Skin from patients with ADEH exhibited significantly (P < .05) lower levels of cathelicidin protein expression than skin from patients with AD. We also found a significant inverse correlation between cathelicidin expression and serum IgE levels (r2 = 0.46, P < .05) in patients with AD and patients with ADEH. CONCLUSION: This study demonstrates that the cathelicidin peptide LL-37 possesses antiviral activity against HSV and demonstrates the importance of variable skin expression of cathelicidins in controlling susceptibility to ADEH. Additionally, serum IgE levels might be a surrogate marker for innate immune function and serve as a biomarker for which patients with AD are susceptible to ADEH. CLINICAL IMPLICATIONS: A deficiency of LL-37 might render patients with AD susceptible to ADEH. Therefore increasing production of skin LL-37 might prevent herpes infection in patients with AD.

Adult↗

Lessons from atopy patch testing in atopic dermatitis.

The exposure of atopic eczema (AE) patients to their relevant protein allergens (eg, from house dust mite, cat dander, grass pollen, or food allergens) can trigger an exacerbation or maintain the disease. Diagnostic procedures are needed to specify allergen avoidance recommendations for the individual patient. Skin prick tests and specific serum IgE tests might be helpful in pointing out potential trigger factors, but relevance needs to be confirmed (eg, with food provocation tests). The atopy patch test (APT) involves the epicutaneous application of intact protein allergens in a diagnostic patch test setting with an evaluation of the induced eczematous skin lesions after 24 to 72 hours. The APT targets the cellular component of AE and helps round out the AE test spectrum. As a number of apparently minor test modifications greatly influence the sensitivity, specificity, and reproducibility of the APT, the European Task Force on Atopic Dermatitis (ETFAD) has developed a standardized APT technique. It consists of purified allergen preparations in petrolatum, applied in 12-mm diameter Finn chambers mounted on Scanpor tape to non-irritated, non-abraded, or tape-stripped skin of the upper back. The APT is read at 48 and 72 hours according to the test criteria and reading key of the ETFAD for appearance of erythema, and number and distribution pattern of the papules. In contrast with skin prick tests, the APT might even detect a relevant sensitization in the absence of specific IgE. Many studies have been undertaken to objectify the sensitivity and specificity of the APT to show its diagnostic use in clinical practice.

Advisory Committees↗

Tacrolimus ointment causes inflammatory dendritic epidermal cell depletion but no Langerhans cell apoptosis in patients with atopic dermatitis.

BACKGROUND: The topical immunomodulators tacrolimus and pimecrolimus are novel therapeutic options for atopic dermatitis (AD). The inhibition of nuclear factor of activated T cell-dependent proinflammatory cytokine production in cutaneous lymphocytes is an established effect of topical immunomodulators, which additionally influence mast cells, eosinophils, and dendritic cells (DCs). The latter include a reduced expression of the high-affinity IgE receptor FcepsilonRI, a reduced stimulatory capacity of lesional DCs, and a selective depletion of the inflammatory dendritic epidermal cells (IDECs) but not of Langerhans cells (LCs) from the lesional skin. OBJECTIVE: Because induction of apoptosis in lymphocytes is a reported tacrolimus effect, we asked whether tacrolimus ointment induces apoptosis of LCs or IDECs in AD lesions. METHODS: Epidermal single-cell suspensions were prepared from AD lesions of 9 tacrolimus-treated and 5 hydrocortisone butyrate-treated patients with AD before and after 1 week of treatment. Cell numbers, apoptosis rate, and immunophenotype were assessed by using the standardized FACS technique with terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, Annexin V, and 3-color immunophenotyping. Freshly isolated LCs and monocyte-derived DCs served as in vitro controls. RESULTS: Tacrolimus and steroid ointment induced a selective depletion of IDECs from the epidermis and reduced the expression of the costimulatory molecules CD80 and CD86. Tacrolimus ointment did not increase the rate of apoptotic DCs, whereas steroid ointment did so. The isolation-induced high apoptosis rate of freshly isolated LCs was unaffected by both drugs. CONCLUSION: Tacrolimus ointment selectively depletes IDECs and alters the immunophenotype of epidermal DCs in AD lesions, but there is no evidence for tacrolimus-induced DC apoptosis in this phenomenon.

Administration, Topical↗

Smallpox, vaccination and adverse reactions to smallpox vaccine.

PURPOSE OF REVIEW: Public fear of the reintroduction of smallpox as a biological weapon or agent of bioterrorism has led to a renaissance of interest in smallpox, and a military and public health vaccination programme in the USA. Clinical experience from the last century together with novel immunobiological findings is the basis for current knowledge on smallpox as a disease. Pre-existing knowledge on smallpox vaccination, plus recent vaccination campaign-derived data, is the basis of current risk-benefit assessments. This article summarizes, from a dermatologist's point of view, current aspects of smallpox, smallpox vaccination and adverse reactions to vaccinia, the live virus smallpox vaccine. RECENT FINDINGS: The smallpox vaccination campaign in the USA has involved over 600,000 vaccinees, and has largely confirmed incidence data on complications. An increased rate of myopericarditis is the new finding in the current vaccination campaign. Immunodeficiencies, manifest atopic dermatitis lesions and a history of atopic dermatitis remain contraindications to vaccination. Plasmacytoid dendritic cells are a key regulator of the human antiviral immune response and are recruited to inflamed skin in many skin diseases, but are depleted in atopic dermatitis lesions. The lack of plasmacytoid dendritic cell recruitment, together with the missing upregulation of antiviral peptides such as cathelicidin LL37 in atopic dermatitis lesions, is considered relevant for an atopic dermatitis patient's susceptibility to eczema vaccinatum. SUMMARY: Recent experience from the US smallpox vaccination campaign has largely confirmed what was known in the 1960s. Current immunobiological research will enhance our understanding of the interaction between poxviruses and the skin's immune system.

Diagnosis, Differential↗

Viral infections in atopic dermatitis: pathogenic aspects and clinical management.

A number of different widespread and disseminated viral infections can occur in patients with atopic dermatitis. Eczema molluscatum is troublesome but not dangerous. Although eczema vaccinatum is rare, it is life-threatening and of increased concern as smallpox vaccinations are reintroduced as a response to possible bioterrorism. There is little information on the course of smallpox itself in atopic dermatitis. Eczema herpeticum is the most common member of this group; recent advances in understanding its pathogenesis might contribute to a more successful management of this serious complication.

Dermatitis, Atopic↗

Atopy patch test reactions show a rapid influx of inflammatory dendritic epidermal cells in patients with extrinsic atopic dermatitis and patients with intrinsic atopic dermatitis.

BACKGROUND: Normal human skin harbors a single epidermal dendritic cell (DC) population, the CD1a(+++)CD11b(-) Langerhans cells. In many chronic inflammatory skin diseases, the epidermal DC pool bears a second population, the CD1a(+)CD11b(+++) inflammatory dendritic epidermal cells (IDECs). Immunophenotypic, ultrastructural, and functional aspects of IDECs have been investigated in chronic untreated skin lesions of intrinsic and extrinsic atopic dermatitis (AD), contact dermatitis (CD), and psoriasis, but little is known about freshly induced early skin lesions. OBJECTIVE: We sought to characterize enumerative and immunophenotypic changes in the epidermal DC pool during the development of eczematous skin lesions. METHODS: The atopy patch test with aeroallergens and food-protein allergens and a conventional patch test with standard-series haptens were performed as models for early skin lesions of extrinsic and intrinsic AD and CD, respectively. After 72 hours, epidermal cell suspensions were prepared, analyzed in a standardized flow cytometric technique, and compared with the results obtained from chronic lesions. RESULTS: The migration of IDECs into the epidermis occurs within 72 hours and is thus an early event. It continues in chronic AD, but not in chronic CD, lesions. The specific upregulation of FcepsilonRI, especially on IDECs, occurs later during formation of extrinsic but not intrinsic AD lesions. LCs were negative for Cd36 in patch test lesions, whereas in chronic skin lesions, LCs expressed Cd36. CONCLUSION: The DC alteration during skin lesion formation can be subdivided into early and late events, with the influx of IDECs as an early event and the alteration of the DC phenotype as a late event.

Adolescent↗

Predisposing factors and clinical features of eczema herpeticum: a retrospective analysis of 100 cases.

BACKGROUND: Eczema herpeticum (EH) is a widespread herpes simplex virus infection of inflamed skin, most often occurring in patients with atopic dermatitis (AD). A monomorphic eruption of dome-shaped blisters and pustules in the eczematous lesions along with severe systemic illness lead to the clinical diagnosis, but atypical variants with disseminated slits may also occur. Topical use of corticosteroids is alleged to be a pathogenetic factor for EH, but predisposing factors for EH are largely unknown. Objective and methods We sought to characterize the clinical features and predisposing factors for EH. A retrospective analysis of 100 patients with EH seen from 1980 through 1996 and of 105 control patients with AD was performed. RESULTS: Fever and lymphopenia were associated with EH, whereas an increased erythrocyte sedimentation rate was frequently seen in patients with EH and control patients who were impetiginized. In 100 patients with EH, primary herpes simplex virus infection was likely in 20 patients, and a secondary herpes simplex virus infection was suggestive in 26 patients. In all, 13 patients had a second EH, whereas 3 patients had a third EH. Patients with EH had a significantly earlier onset of AD and a significantly higher total serum IgE level than the control patients. More than 75% of the patients with EH had not received corticosteroid treatment in the 4 weeks before onset of EH. CONCLUSIONS: The characteristics of patients with EH are those associated with severe manifestations of AD. The majority of EH occurs in patients with untreated AD, arguing against a role for topical corticosteroids in the development of EH.

Adult↗

Expression and function of the mannose receptor CD206 on epidermal dendritic cells in inflammatory skin diseases.

The capability to take up mannosylated protein antigens is important for the biologic function of dendritic cells, as many glycoproteins derived from bacteria and fungi, e.g., Malassezia furfur, are mannosylated. The expression of the mannose receptor CD206 has been regarded a differentiation hallmark of immature dendritic cells, whereas monocytes and mature dendritic cells as well as epidermal Langerhans cells do not express CD206. This study describes some epidermal dendritic cells that may express CD206 under inflammatory skin conditions: Immunohistochemical and flow cytometric analysis with the CD206-specific D547 antibody confirmed that Langerhans cells from normal human skin do not express CD206. Epidermal cell suspensions from atopic dermatitis and psoriasis revealed two distinct subsets of epidermal dendritic cells: a CD1a(+++)/CD206(-) cell population (i.e., Langerhans cells) and a CD1a(+)/CD206(++) cell population, corresponding to the previously described inflammatory dendritic epidermal cells. CD206-mediated endocytosis, assessed by dextran-fluorescein isothiocyanate uptake, was demonstrated in inflammatory dendritic epidermal cells but not in Langerhans cells. CD206-independent uptake of the fluorescent dye Lucifer yellow, a pinocytosis marker, was demonstrated in both Langerhans cells and inflammatory dendritic epidermal cells. Electron microscopic examination, known to distinguish Langerhans cells from inflammatory dendritic epidermal cells by their Birbeck granules, revealed Langerhans cells with Birbeck granules and inflammatory dendritic epidermal cells without Birbeck granules. Inflammatory dendritic epidermal cells exhibited numerous coated pits and vesicles, the latter fusing with large endosome-like structures, thus suggesting a high endocytotic activity. Immunogold staining with D547 monoclonal antibody confirmed that inflammatory dendritic epidermal cells were positive for CD206. In conclusion, inflammatory dendritic epidermal cells but not Langerhans cells are expressing CD206 in situ and use it for receptor-mediated endocytosis.

Cell Differentiation↗

Enhanced expression and activity of protein-tyrosine kinases establishes a functional signaling pathway only in FcepsilonRIhigh Langerhans cells from atopic individuals.

The trimeric high-affinity IgE receptor (FcepsilonRI) on human epidermal Langerhans cells mediates IgE-dependent antigen uptake and subsequent antigen focusing. Its expression is upregulated on Langerhans cells (FcepsilonRIhigh Langerhans cells) and inflammatory dendritic epidermal cells (FcepsilonRIhigh inflammatory dendritic epidermal cells) in the skin of patients with atopic dermatitis. In the absence of the amplifying beta-chain in these cells, FcepsilonRI signaling (indicated by calcium mobilization and activation of the transcription factor nuclear factor-kappaB) is only detectable in FcepsilonRIhigh Langerhans cells from atopics, but not FcepsilonRIlow Langerhans cells from nonatopics. Therefore we investigated protein-tyrosine kinases putatively involved in FcepsilonRI signaling in Langerhans cells and asked whether differences in their expression and FcepsilonRI-induced activity could explain the dichotomic responses observed in atopic vs nonatopic individuals. First, we found the src protein-tyrosine kinases p53/56lyn, p59fyn, p56/59hck, p55c-fgr, and p60c-src to be expressed in Langerhans cells from all donors. In addition, whereas p56lck was lacking, p72syk and the negative regulatory p50csk were detected. Upon terminal maturation of Langerhans cells in vitro, no significant change of the protein- tyrosine kinase expression profile except downregulation of p56/59hck was observed. In contrast, significant upregulation of all protein-tyrosine kinase expressed except p50csk was detected in FcepsilonRIhigh Langerhans cells, but not in FcepsilonRIhigh inflammatory dendritic epidermal cells. Finally, the important protein-tyrosine kinases substrate phospholipase C-gamma1, which is also essential for downstream calcium mobilization, was only phosphorylated upon FcepsilonRI triggering in FcepsilonRIhigh Langerhans cells from atopics, but not in FcepsilonRIlow Langerhans cells from nonatopics. Therefore, upregulation of FcepsilonRI and protein-tyrosine kinase expression as well as subsequent protein-tyrosine kinase activity may explain, at least in part, that an efficient signaling pathway in terms of calcium mobilization is restricted to FcepsilonRIhigh Langerhans cells from atopic individuals. Key words:

Cell Line↗

Plasmacytoid dendritic cells: a new cutaneous dendritic cell subset with distinct role in inflammatory skin diseases.

Epidermal dendritic cells found in inflamed skin include Langerhans cells and the recently identified population of inflammatory dendritic epidermal cells. Another subset of dendritic cells in humans is the plasmacytoid dendritic cell in peripheral blood, which is characterized by the production of large amounts of type I interferon (interferon-alpha and interferon-beta) upon viral infection. We hypothesized that plasmacytoid dendritic cells might be involved in anti-viral defense mechanisms of the skin. Here we investigated plasmacytoid dendritic cells, inflammatory dendritic epidermal cells, and Langerhans cells in epidermal single cell suspensions of normal looking skin from healthy volunteers and of lesional skin from patients with different inflammatory skin diseases. Langerhans cells were found in normal and in inflamed skin samples. In normal skin, plasmacytoid dendritic cells and inflammatory dendritic epidermal cells were low or absent. Lesional skin samples from patients with psoriasis vulgaris and contact dermatitis contained relatively high numbers of both inflammatory dendritic epidermal cells and plasmacytoid dendritic cells. In contrast, many inflammatory dendritic epidermal cells but only very few plasmacytoid dendritic cells could be detected in atopic dermatitis lesions. Lupus erythematosus was characterized by high numbers of plasmacytoid dendritic cells but low numbers of inflammatory dendritic epidermal cells. These results demonstrate that in addition to resident Langerhans cells, plasmacytoid dendritic cells and inflammatory dendritic epidermal cells are selectively recruited to the skin lesions depending on the type of skin disease. The lack of plasmacytoid dendritic cells in atopic dermatitis may predispose atopic dermatitis patients to viral infections such as eczema herpeticum, a secondary infection of atopic dermatitis lesions with herpes simplex virus. The composition of dendritic cell subsets may help to clarify the etiology of inflammatory skin diseases and forms the basis for therapeutic intervention with selective microbial molecules such as immunostimulatory CpG oligonucleotides.

Cell Lineage↗

Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone butyrate ointment in adult patients with atopic dermatitis.

BACKGROUND: Vehicle-controlled studies have demonstrated the efficacy and safety of tacrolimus ointment for patients with atopic dermatitis. OBJECTIVE: This study was undertaken to compare 0.03% and 0.1% tacrolimus ointment with 0.1% hydrocortisone-17-butyrate ointment, a midpotent to potent topical corticosteroid, in the treatment of adult patients with moderate-to-severe atopic dermatitis. METHODS: Patients applied ointment twice daily to all affected areas for 3 weeks in this multicenter, randomized, double-blind, parallel-group study. The primary endpoint was the modified eczema area and severity index (mEASI) mean area under the curve as a percentage of baseline. RESULTS: Five hundred seventy patients were randomized and received treatment. Discontinuations included 22 of 193 patients from the 0.03% tacrolimus group, 22 of 191 patients from the 0.1% tacrolimus group, and 17 of 186 patients from the hydrocortisone butyrate group. The median mEASI mean area under the curve as a percentage of baseline was 47.0%, 36.5%, and 36.1% for patients who received 0.03% tacrolimus, 0.1% tacrolimus, and 0.1% hydrocortisone butyrate, respectively. There was no statistically significant difference between 0.1% tacrolimus and 0.1% hydrocortisone butyrate; however, the lower improvement in mEASI for 0.03% tacrolimus was statistically significant when compared with 0.1% tacrolimus (P <.001) or hydrocortisone butyrate (P =.002). Skin burning and pruritus at the application site showed a higher incidence in the tacrolimus treatment groups than in the hydrocortisone butyrate group (P <.05). Laboratory parameters showed no treatment differences and no marked changes over time. CONCLUSIONS: The efficacy of 0.1% tacrolimus ointment was similar to that of 0.1% hydrocortisone butyrate ointment and was lower for 0.03% tacrolimus ointment. No serious safety concerns were identified.

Administration, Topical↗

Long-lasting "christmas tree rash" in an adolescent: isotopic response of indeterminate cell histiocytosis in pityriasis rosea?

A 13-year-old girl developed a non-pruritic pityriasis rosea-like rash, which did not respond to topical corticosteroids or UV therapy but persisted for 2 years. The lymphohistiocytic infiltrate in the upper dermis showed mononuclear cells immunoreactive with S100, CD68, factor XIIIa and CD1a. Electron microscopic evaluation of these cells demonstrated lamellated dense bodies but no Birbeck granules, lipid vacuoles or cholesterol crystals. Two diagnoses were made: a primarily clinical diagnosis of generalized eruptive histiocytosis and a more cell-biology-based diagnosis of an indeterminate cell histiocytosis. Three years later, the lesions are showing spontaneous resolution, with loss of erythema and flattening. Our patient's indeterminate cells fulfil Rowden's classical definition (dendritically shaped epidermal non-keratinocytes without identifying cytoplasmic features), as well as Zelger's newer definition (cells with features of both macrophages and dendritic cells). A Christmas tree pattern has not been previously described in indeterminate cell histiocytosis. Development of indeterminate cell histiocytosis in the lesions of a healing pityriasis rosea might explain the unusual distribution pattern. The development of a skin disorder at the site of an unrelated, already healed skin disease is known as an isotopic response. Key

Adolescent↗

Phacomatosis pigmentokeratotica (Happle) in a 23-year-old man.

Phacomatosis pigmentokeratotica is a rare but highly characteristic disease defined by the occurrence of an organoid naevus with sebaceous differentiation, a speckled-lentiginous naevus and other associated anomalies. It is probably caused by the twin-spot phenomenon. We report on a 23-year-old male electrician with 10 irregularly shaped, sharply demarcated, brownish-yellow papillomatous plaques following Blaschko's lines, as well as 6 large, sharply demarcated, round to oval, slightly greyish macules with pewit-egg-like dots, involving both buttocks, the right thigh, the right knee, the right pectoral region and the upper back. A moderate hyperhidrosis of the palms, soles and axillae was noted. All routine blood tests and laboratory findings, including chest X-ray, ECG, abdominal ultrasound, ocular and neural examination were unrevealing. Phacomatosis pigmentokeratotica may be associated with dysaesthesia, segmental hyperhidrosis, mild mental retardation, epileptic seizures, deafness, ptosis, strabismus or muscular weakness. In our patient, only slight hyperhidrosis was present, whereas all other associated anomalies could be excluded.

Adult↗

Immunomodulatory macrolactams for topical treatment of inflammatory skin diseases.

Tacrolimus (FK-506; Fujisawa Pharmaceutical Co Ltd) and pimecrolimus (SDZ-ASM-981; Novartis AG) are topical immunomodulators, which provide an alternative to glucocorticosteroids for the topical treatment of atopic dermatitis and other inflammatory dermatoses. Both substances form a complex with cytosolic immunophilins. The complex blocks calcineurin and inhibits the transcription of NF-AT-dependent pro-inflammatory cytokine genes. Multicenter, randomized, double-blind clinical trials have shown the efficacy of both substances in atopic dermatitis. We review the physicochemical characteristics, mode of action, pharmacokinetic data, side effects, results of the clincal trials and further indications for tacrolimus and pimecrolimus.

Adjuvants, Immunologic↗

Topical treatment with imiquimod may induce regression of facial keratoacanthoma.

Keratoacanthoma (KA) is a rapidly growing tumour histologically resembling squamous cell carcinoma. Although it may regress spontaneously, KA is routinely treated by excision or radiation therapy. Here we report on the successful therapeutic use of imiquimod for the treatment of KA. Four patients with a one to six week history of facial KA were treated with imiquimod cream 5 % every second day for four to 12 weeks. In each patient, KA fully regressed under topical treatment with imiquimod. In three of the patients, KA had disappeared within four to six weeks. In two patients, disappearance was confirmed histologically. No recurrence occurred during a four- to six-month follow-up-period. Our observations indicate that topical immunostimulation with imiquimod may induce or promote immune defence mechanisms leading to KA regression. Imiquimod might therefore prove to be an effective non-invasive treatment modality for KA that warrants more extensive evaluation by clinical studies.

Adjuvants, Immunologic↗