Successful treatment with oral isotretinoin of acneiform skin lesions associated with cetuximab therapy.
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Adult↗
Biomedical subjects
A Kapp
Publications and source records attributed to A Kapp.
Sentinel node biopsy in melanoma delays recurrence but does not change melanoma-related survival: a retrospective analysis of 673 patients.
BACKGROUND: The status of the sentinel lymph node (SLN) is an important parameter to predict the prognosis of melanoma patients but it is a matter of debate if removal of micrometastases by SLN biopsy (SLNB) influences the prognosis of melanoma patients. OBJECTIVES: We sought to investigate the impact of SLNB in melanoma patients with regard to recurrence-free survival, overall survival and metastatic pathways. PATIENTS AND METHODS: We studied, retrospectively, 673 melanoma patients with a primary melanoma (tumour thickness > or = 1 mm) and without clinical evidence of metastases at the time of melanoma diagnosis. In 377 patients the melanoma was removed without SLNB between January 1995 and March 2000 (pre-SLNB group). In 296 patients the melanoma was removed with SLNB between April 2000 and March 2003 (SLNB group). Otherwise, both groups received identical surgical treatment of the primary melanoma and initial staging procedures performed by the same team of physicians. Follow-up recommendations were also identical in both groups. RESULTS: Both groups showed no significant differences with regard to characteristics of the primary melanoma, sex and age. By Kaplan-Meier analyses, melanoma-related overall survival was comparable in both groups. However, recurrence-free survival was increased in pre-SLNB patients due to significantly fewer regional lymph node metastases, whereas frequencies of locoregional cutaneous and distant metastases were comparable in both groups. CONCLUSIONS: SLNB advances the detection of regional lymph node metastases and therefore avoids nodal recurrences but does not influence metastatic behaviour of melanoma cells and does not protect patients from melanoma-related death caused by distant metastases. Thus, our retrospective data favour the marker hypothesis for melanoma metastasation. To elucidate further if subgroups of patients benefit from SLNB, prospective randomized studies with long-term follow-up are needed.
Adolescent↗
Alpha-toxin is produced by skin colonizing Staphylococcus aureus and induces a T helper type 1 response in atopic dermatitis.
BACKGROUND: Staphylococcus aureus is a well known trigger factor of atopic dermatitis (AD). Besides the superantigens, further exotoxins are produced by S. aureus and may have an influence on the eczema. OBJECTIVE: To explore the impact of staphylococcal alpha-toxin on human T cells, as those represent the majority of skin infiltrating cells in AD. METHODS: Adult patients with AD were screened for cutaneous colonization with alpha-toxin producing S. aureus. As alpha-toxin may induce necrosis, CD4(+) T cells were incubated with sublytic alpha-toxin concentrations. Proliferation and up-regulation of IFN-gamma on the mRNA and the protein level were assessed. The induction of t-bet translocation in CD4(+) T cells was detected with the Electrophoretic Mobility Shift Assay. RESULTS: Thirty-four percent of the patients were colonized with alpha-toxin producing S. aureus and alpha-toxin was detected in lesional skin of these patients by immunohistochemistry. Sublytic alpha-toxin concentrations induced a marked proliferation of isolated CD4(+) T cells. Microarray analysis indicated that alpha-toxin induced particularly high amounts of IFN-gamma transcripts. Up-regulation of IFN-gamma was confirmed both on the mRNA and the protein level. Stimulation of CD4(+) T cells with alpha-toxin resulted in DNA binding of t-bet, known as a key transcription factor involved into primary T helper type 1 (Th1) commitment. CONCLUSION: alpha-toxin is produced by S. aureus isolated from patients with AD. We show here for the first time that sublytic alpha-toxin concentrations activate T cells in the absence of antigen-presenting cells. Our results indicate that alpha-toxin is relevant for the induction of a Th1 like cytokine response. In AD, this facilitates the development of Th1 cell dominated chronic eczema.
Adult↗
Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis.
BACKGROUND: Eosinophils may play an important role in the pathogenesis of atopic dermatitis (AD). Interleukin-5 is essential for eosinophil growth, differentiation and migration. A monoclonal antibody to human interleukin-5 (mepolizumab) was developed for atopic diseases. This study was designed to study the effect of mepolizumab in AD. METHODS: Two single doses of 750 mg mepolizumab, given 1 week apart, were studied in patients with moderate to severe AD using a randomized, placebo-controlled parallel group design. The primary endpoint of 'success' to treatment was defined as the percentage of patients with at least 'marked improvement' after 2 weeks as assessed by the Physician's Global Assessment of Improvement (PGA). Furthermore, SCORing AD (SCORAD), pruritus scoring, number of blood eosinophils and serum thymus and activation-regulated chemokine (TARC) values served as secondary endpoints. Fluticasone propionate cream 0.05%, once daily could be used as rescue medication from day 16 if no improvement was recorded. RESULTS: Eighteen patients received mepolizumab and 22 placebo treatment. Peripheral blood eosinophil numbers were significantly reduced in the treatment group compared with placebo (P < 0.05). No clinical success was reached by PGA assessment (P = 0.115), SCORAD (P = 0.293), pruritus scoring and TARC values in the mepolizumab-treated group compared with placebo. However, modest improvement (<50% improvement) assessed by PGA was scored significantly more in the mepolizumab-treated group compared with placebo (P < 0.05). CONCLUSION: Two single doses of 750 mg mepolizumab did not result in clinical success in patients with AD, despite a significant decrease in peripheral blood eosinophils.
Adult↗
Differential pattern of CCR1 internalization in human eosinophils: prolonged internalization by CCL5 in contrast to CCL3.
BACKGROUND: Whereas recent studies underlie the fundamental importance of the CC chemokine receptor 3 (CCR3) for the recruitment of eosinophils in allergic diseases, controversial data exist about the relevance of CCR1 on eosinophils. Therefore, the purpose of this study was to investigate the expression and regulation of CCR1 on eosinophils. METHODS: Flow cytometric analysis of whole blood eosinophils and CD16-negative selected eosinophils from healthy nonatopic donors and from patients with atopic disorders was performed and CCR1 receptor internalization and re-expression were studied. RESULTS: Flow cytometric analysis of whole blood eosinophils revealed that 17.8% of the donors expressed high levels of CCR1 (CCR1high) and 82.2% low levels of CCR1 (CCR1low). A significant down-regulation of CCR1 was induced by 24 h preincubation of isolated eosinophils from CCR1high donors either with IL-3, CC chemokine ligand 3 (CCL3), CCL5, CCL7, or CCL13. Internalization experiments using eosinophils from CCR1high donors revealed that CCL5 is more effective to induce CCR1 internalization than CCL3. Whereas CCR1 re-expression after stimulation with CCL3 reached prestimulation levels (120 min: 81.3% relative CCR1 surface expression) CCL5 induced a prolonged CCR1 internalization (120 min: 15.7%). CONCLUSIONS: This study demonstrates a distinct pattern of CCR1 internalization and re-expression in human eosinophils between CCL3 and CCL5, as CCL5 induces a prolonged CCR1 internalization and the basic value is not reached after 24 h. Since prolonged receptor internalization plays a central role in chemokine-mediated inhibition of receptor function, CCR1 seems to be an attractive target on human eosinophils for chemokine receptor blockade besides CCR3.
Chemokine CCL5↗
[New therapeutic strategies for the different subtypes of urticaria].
Urticaria is one of the most common skin diseases. It is divided into several categories including acute and chronic urticaria as well as physical urticaria and special subtypes such as cholinergic and autoimmune urticaria. The causes of urticaria are multiple. In more than 80%, urticaria is triggered by an inflammatory focus, a subclinical infection or autoimmune actions. In addition, non-specific pharmacological or toxin-mediated release of inflammatory mediators from basophils or mast cells can also trigger urticaria. These new aspects in the pathophysiology of urticaria suggest new and promising therapeutic strategies. The first line treatment of urticaria still consists of non-sedating H1-antihistamines. Since urticaria has a profound impact on quality of life, effective treatment is very important. We consider new therapeutic options based on our long-term experience in treating patients with urticaria.
Administration, Oral↗
[Chronic urticaria in childhood].
Chronic urticaria in children occurs more often than it might be supposed, but its management is not part of the usual daily routine. While acute urticaria in children can be treated symptomatically without further investigations, chronic urticaria requires a search for trigger factors. Autoimmune urticaria can occasionally be documented in children. The treatment of chronic urticaria depends on the suspected trigger, always keeping in mind that medications may need to be adjusted to meet pediatric requirements.
Age Factors↗
[Specific immunotherapy. Hyposensitization with allergens].
Successful allergen-specific immunotherapy (SIT) induces complex immunologic chan-ges resulting in reduced allergic inflammatory reactions. SIT has long-term effects in mild forms of inhalant allergies and is effective even when standard pharmacotherapy fails. Moreover, the risk to develop additional allergic sensitizations and the development of asthma is significantly reduced in children with allergic rhinitis. SIT is the treatment of choice in patients with systemic reactions to hymenoptera venoms. Although the exact effector mechanisms of SIT still have to be clarified, the most probable effect is a modulation of regulatory T cells associated with a switch of allergen-specific B-cells towards IgG4 production. The critical point to insure efficacy and safety is the selection of patients and allergens, task best performed by a specialist trained in allergology. Further details are available in the position papers of the German allergy societies - DGAI(Deutsche Gesellschaft fiir Allergologie und Klinische Immunologie) and ADA (Arzte-verband Deutscher Allergologen) - which can be found at www.dgaki.de.
Adolescent↗
[Successful treatment of skin and lung sarcoidosis with fumaric acid ester].
A 61-year old female patient with cutaneous sarcoidosis was treated with fumaric acid esters (Fumaderm). After 12 months of therapy, lesions were markedly improved and treatment was discontinued. 18 months later, the cutaneous lesions recurred, angiotensin converting enzyme (ACE) serum levels were increased and a chest X-ray demonstrated pulmonary involvement. Therapy with fumaric acid esters was again started. The skin showed improvement after 2 months and completely cleared within 17 months, within 4 months ACE levels normalized, and within 10 months radiologic changes markedly resolved. This case demonstrates a possible role for fumaric acid esters not only in the treatment of cutaneous but also systemic sarcoidosis.
Dermatologic Agents↗
T-helper 2 cytokines attenuate senescent eosinophil activation by the CXCR4 ligand stromal-derived factor-1alpha (CXCL12).
BACKGROUND: Different chemokine receptors have been suggested to play a pivotal role in allergic diseases and therefore to be relevant for the activation of effector cells and propagation of the inflammatory response. The CXC chemokine receptor CXCR4 has recently been found on the surface of eosinophils implicating a role in allergic diseases. OBJECTIVE: The aim of this study was to investigate the functional expression of CXCR4 on senescent eosinophils. Moreover, we questioned whether the cytokine profile--T-helper (Th)1 and Th2 cytokines--affect the activation of eosinophils via the CXCR4 that could be important for the different phases of the allergic reaction. METHODS: CXCR4 expression on human eosinophils was analysed by flow cytometry and RT-PCR. Functional analyses of intracellular calcium fluxes, actin polymerization, release of reactive oxygen species and, chemotaxis were carried out using spectrofluorometry, flow cytometry, chemiluminescence and modified Boyden chamber technique. RESULTS: Whole blood and freshly isolated eosinophils weakly express CXCR4 surface protein. Incubation in culture medium without addition of cytokines for 24 h always lead to strong CXCR4 surface expression that paralleled with stromal-derived factor-1alpha (CXCL12)-induced eosinophil activation. Stimulation of eosinophils with CXCL12 leads to an internalization of CXCR4, which could be prevented by phenylarsine oxide. Co-incubation of eosinophils with Th2 cytokines such as IL-3, IL-4, IL-5, IL-13, and granulocyte macrophage-colony stimulating factor prevented the expression of CXCR4 and affected eosinophil activation after stimulation with the CXCR4 ligand CXCL12. From these cytokines, IL-3 was the only cytokine completely inhibited intracellular calcium fluxes and chemotaxis of eosinophils in response to CXCL12. CONCLUSION: Senescent eosinophils express functional CXCR4 receptors, which are prevented by Th2 cytokines that are found in the early phase of allergic reaction. Therefore, CXCR4 activation of eosinophils seems to be important in the chronic phase of allergic reaction, which is dominated by a Th1 cytokine profile.
Cells, Cultured↗
Late eczematous reactions to food in children with atopic dermatitis.
BACKGROUND: Food allergy is a common problem in patients with atopic dermatitis (AD), particularly in children. While immediate reactions to food are well characterized, the importance of food as a provocation factor for late eczematous reactions has been a subject of debate for several decades. OBJECTIVE: To investigate the importance of food for the induction of late eczematous reactions in children with AD and to correlate the clinical outcome to the results of specific IgE determinations and atopy patch tests (APTs). METHODS: One hundred and six double-blind placebo-controlled food challenges (DBPCFCs) to cow's milk, hen's egg, wheat and soy in 64 children with AD (median age 2 years) were analysed retrospectively. Total and food-specific IgE were determined by CAP RAST FEIA and APTs with native foodstuff were performed. The diagnostic values of specific IgE and APT results were calculated. RESULTS: Forty-nine (46%) of the challenges were related to a clinical reaction. An exacerbation of AD (late eczematous reaction) commonly occurred 24 h after the ingestion of food. Isolated late eczematous reactions were seen in 12% of all positive challenges. Forty-five percent of the positive challenges were associated with late eczematous responses, which followed immediate-type reactions. The sensitivity of food-specific IgE and the APT was 76% and 70%, respectively. Specific IgE and APT were often false positive, which resulted in low positive predictive values (64% and 45%, respectively). CONCLUSIONS: Late eczematous reactions may often be observed upon food challenge in children with AD. Due to the poor reliability of food-specific IgE and APT results DBPCFCs have still to be regarded as the gold standard for the appropriate diagnosis of food responsive eczema in children with AD.
Child, Preschool↗
Birch pollen-related food as a provocation factor of allergic symptoms in children with atopic eczema/dermatitis syndrome.
BACKGROUND: Food allergy to cow's milk or hen's egg is a common problem in children with atopic eczema/dermatitis syndrome (AEDS) but the role of birch pollen-related food for the induction of allergic symptoms is still not clear. PATIENTS/METHODS: Twelve children (median age 5 years) with AEDS underwent an oral challenge with those birch pollen-related foods which were reported to induce no immediate symptoms, but were consumed on a regular basis. Total IgE and specific IgE to birch pollen, Bet v 1/2 and various birch pollen-related foods were determined. RESULTS: Seven of 12 children showed immediate and/or late eczematous reactions upon ingestion of birch pollen-related foodstuff. Four children showed a worsening of eczema 24 h upon oral challenge with a significant difference in SCORAD before and after challenge. There were no differences in terms of total IgE or birch pollen-specific IgE between children with a late eczematous response and non-reacting children. CONCLUSIONS: Birch pollen-related food may induce allergic symptoms in children with AEDS who exhibit a sensitization to birch pollen. Oral challenge tests should be performed in those children who suffer from severe AEDS and who are highly sensitized to birch pollen allergens even in the absence of a history suggestive of food allergy.
Allergens↗
[The impact of food allergy in patients with atopic dermatitis].
Besides other trigger factors food allergens have been shown to play a major role in the exacerbation and maintenance of eczematous lesions in patients with atopic dermatitis (AD), particularly in children. Food allergy may not only present as a flare up up of eczema in these patients, but also immediate type reactions and mixed reactions can be observed under food challenge tests. Whereas cow's milk hen's egg, wheat and soy have been identified as important triggers in infants, pollen related foods like nuts, fruit und vegetable have a greater impact in adolescents and adult Food specific T cells have been identified as effector cells in food responsible eczema and food specific T cell clones could be generated from lesional skin of patients who reacted with a worsening of their AD upon oral challenge tests. Due to the poor reliability of in-vitro (RAST) and skin tests (skin prick test (SPT), atopy patch test (APT)) the double blind placebo controlled food challenge (DBPCFC) is regarded as the gold standard in the diagnostic work-up of food allergy. Once a food allergy has been diagnosed, a specific elimination diet represents the first line therapy, which has to consider the supplementation of essential nutrients.
Adult↗
[Systemic therapy of atopic dermatitis].
The optimal treatment of atopic dermatitis requires regular medical supervision. The course of this chronic skin disease is influenced by multiple triggers which are relevant for the treatment. The mainstays of topical therapy include regular use of emollients coupled with antimicrobial substances, corticosteroids and immune modulators as required. Ultraviolet radiation and immunosuppressive regimens represent further options for the treatment of severe exacerbations and may lead to long term improvement. Data from experimental studies provide insight into possible future treatment methods.
Adjuvants, Immunologic↗
[Successful topical treatment of cutaneous sarcoidosis with tacrolimus].
A 56-year old female patient with cutaneous sarcoidosis in the face was treated with fumaric acid esters and doxycycline without any effect. Topical tacrolimus led clinically and histologically to a nearly complete remission within three months, which continued after 4 months of follow-up.
Biopsy↗
[Atopic dermatitis. Version (17 July 2002 - modified final version)].
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Ambulatory Care↗
Atopic dermatitis management with tacrolimus ointment (Protopic).
Tacrolimus ointment is the first of a new class of non-steroidal topical immunomodulators indicated for the treatment of atopic dermatitis. Topical tacrolimus has been subject to an extensive clinical development program involving more than 16,000 patients. A clinical trial program, including vehicle-controlled studies, short- and long-term comparative studies and long-term safety studies, has investigated tacrolimus 0.1% and 0.03% ointment for the treatment of atopic dermatitis in adults and children aged 24 months and older. Tacrolimus monotherapy is rapidly effective, resulting in clinical improvements within three days of starting therapy, and produces a progressive increase in efficacy that is sustained during long-term treatment. Tacrolimus treats the signs and symptoms of atopic dermatitis, reduces the incidence of flares, and offers the potential for long-term disease control. No major safety concerns have been reported to date. Tacrolimus ointment is generally well tolerated, the primary adverse events being mild to moderate and transient application-site reactions: skin burning, pruritus and erythema. Tacrolimus ointment is a significant advance in dermatology and provides physicians with an alternative to conventional topical corticosteroid therapy.
Adolescent↗
[Hexadactyly of hand and feet in a patient with basal cell nevus syndrome].
A 35-year-old male patient with hexadactyly on the right hand and both feet presented with multiple basal cell carcinomas of the skin. The results of further investigations led to the diagnosis of basal cell nevus syndrome (BCNS). The basal cell nevus syndrome (Gorlin-Goltz syndrome) characterized by multiple basal cell carcinomas, odontogenic cysts, skeletal abnormalities and associated neoplasms belongs to the group of genodermatoses. Reviewing the current literature we discuss aspects of the pathogenesis of the basal cell nevus syndrome as well as diagnosis criteria and treatment options.
Acitretin↗