[Hyperpigmentation of the abdominal skin. Diagnosis: Morbus Gougerot-Carteaud PCR].
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Abdominal Wall↗
Biomedical subjects
L R Braathen
Publications and source records attributed to L R Braathen.
[Anti-interleukin-5 therapy for eosinophilic diseases].
In a number of diseases with eosinophilia, elevated interleukin (IL)-5 levels are detected in the peripheral blood and/or tissues. IL-5 plays an important role in regulating the production, differentiation, recruitment, activation, and survival of eosinophils. Therefore, neutralizing IL-5 by blocking antibodies seems a promising approach in the treatment of eosinophilic diseases. Clinical trials have demonstrated that anti-IL-5 therapy results in a rapid decrease in peripheral blood eosinophil numbers. Moreover, improvement of symptoms in patients with lymphocytic variants of hypereosinophilic syndromes, in eosinophilic esophagitis and chronic rhinitis with nasal polyposis has been observed. In contrast, in patients with bronchial asthma or atopic eczema, anti-IL-5 therapy showed only moderate or no clinical effects. Future studies will have to identify those eosinophilic diseases in which anti-IL-5 antibodies are effective, perhaps with the help of newly developed biomarkers.
Animals↗
Eosinophilic esophagitis in adults--no clinical relevance of wheat and rye sensitizations.
BACKGROUND: Eosinophilic esophagitis (EE) is often associated with concomitant atopic diseases. In children with EE in whom food allergens have been identified as causative factors, elemental and elimination diets result in an improvement or resolution of symptoms. Most adult EE patients are sensitized to aeroallergens, which cross-react with plant-derived food allergens, most commonly to grass pollen and cereals. AIMS OF THE STUDY: To investigate the clinical relevance of the sensitization to wheat and rye, and the efficacy of an allergen-specific elimination diet in adult EE patients. METHODS: Six patients (five men, one women) with permanently active EE sensitized to grass pollen and the cereals wheat and rye underwent a double-blind placebo-controlled food challenge and were kept on an elimination diet avoiding wheat and rye for 6 weeks. RESULTS: The challenge tests with wheat and rye did not provoke any EE symptoms in all patients. The elimination diet failed in reducing disease activity. Although one patient noticed an improvement of symptoms, endoscopic and histopathologic findings remained unchanged. CONCLUSIONS: In adult EE patients, sensitization to wheat and rye does not seem causative for EE. Elimination diet is not a reliable and efficient therapeutic measure in EE patients sensitized to wheat and rye. Low specific immunoglobulin-E levels to wheat and rye may be a consequence of the underlying grass pollen allergy.
Adult↗
Oral prednisolone induced acute generalized exanthematous pustulosis due to corticosteroids of group A confirmed by epicutaneous testing and lymphocyte transformation tests.
BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption which is often provoked by drugs. CASE REPORT: We report 2 cases of AGEP which showed rapidly spreading pustular eruptions accompanied by malaise, fever and neutrophilia after the administration of systemic prednisolone (corticosteroid of group A, hydrocortisone type). The histological examination showing neutrophilic subcorneal spongiform pustules was consistent with the diagnosis of AGEP. In both cases the rash cleared within a week upon treatment with topical steroids (corticosteroid of group D1, betamethasonedipropionate type and corticosteroid of group D2, hydrocortisone-17-butyrate type). Three months after recovery, the sensitization to corticosteroids of group A was confirmed by epicutaneous testing and positive lymphocyte transformation tests. CONCLUSION: These cases show that systemic corticosteroids can induce AGEP and demonstrate that epicutaneous testing and lymphocyte transformation tests may be helpful in identifying the causative drug. Our data support previous reports indicating an important role for drug-specific T cells in inducing neutrophil inflammation in this disease.
Administration, Oral↗
[Persistent erythematous nodule on the back of the hand].
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Adult↗
5-aminolaevulinic acid photodynamic therapy in a transgenic mouse model of skin melanoma.
Photodynamic therapy (PDT) is widely used to treat preneoplastic skin lesions and non-melanoma skin tumours. Studies analyzing the effects of PDT on malignant melanoma have yielded conflicting results. On the one hand, melanoma cell lines in culture as well as cell lines transplanted into experimental animals were sensitive to PDT. On the other hand, spontaneous melanomas of human patients responded poorly to most PDT regimens tested so far. Here, we analyzed effects of 5-aminolaevulinic acid (5-ALA)-based PDT on melanoma cell lines and on experimental melanomas. To mimic the clinical situation as closely as possible, metallothionein-I/ret (MT-ret) mice, a transgenic model of skin melanoma development, were used. Optimal doses of 5-ALA as well as energy doses and power densities were determined in vitro using a cell line (Mel25) established by us from a melanoma of an MT-ret transgenic mouse as well as commercially available human and mouse melanoma cell lines. Treatment with light irradiation alone had no effect. In combination with 5-ALA, however, this illumination readily induced the death of all mouse and human melanoma cell lines examined. Still, 5-ALA PDT caused only minor focal regressive changes including haemorrhages and fibrosis of MT-ret melanomas in vivo and did not significantly delay tumour growth. These results show that, even though MT-ret melanoma cells are vulnerable to 5-ALA PDT in vitro, malignant MT-ret melanomas in vivo are quite resistant to this type of therapy at doses which are highly effective in vitro.
Aminolevulinic Acid↗
Inflammatory cell numbers and cytokine expression in atopic dermatitis after topical pimecrolimus treatment.
BACKGROUND: In several clinical trials the topical application of pimecrolimus was shown to be effective in the treatment of atopic dermatitis (AD). By targeting calcineurin-dependent signaling pathways, pimecrolimus controls cytokine gene expression. The purpose of this study was to investigate the effect of pimecrolimus on the inflammatory infiltrate and cytokine expression pattern in AD upon topical therapy. METHODS: From 10 patients with acute AD, skin biopsies as well as immunophenotype and cytokine production of peripheral blood mononuclear cells (PBMC) were examined before and 3 weeks after therapy. RESULTS: The clinical improvement was associated with a marked regression of histopathological features. In particular, the density of the inflammatory infiltrate mostly containing lymphocytes and eosinophils declined. By double immunofluorescent staining, a reduced expression of the T helper (Th) 2 cytokines interleukin (IL)-5, IL-10, and IL-13 in both CD4+ and CD8+ T cells was demonstrated after therapy. Pimecrolimus therapy was also associated with a reduced expression of the Th1 cytokine interferon (IFN)-gamma. Interestingly, the numbers of epidermal CD1a+ dendritic cells increased following treatment. In the peripheral blood, a decrease of lymphocytes and eosinophils was noticed, but the distribution of lymphocyte subpopulations and their capacity of cytokine production did not change. CONCLUSIONS: Topical pimecrolimus exhibits anti-inflammatory effects in AD by reducing the inflammatory cell infiltrate and cytokine expression in the dermis.
Administration, Topical↗
Successful treatment of pityriasis lichenoides with topical tacrolimus.
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Child↗
Characterization of the cellular infiltrate during successful topical treatment of lentigo maligna with imiquimod.
Lentigo maligna (LM) is an in situ melanoma which usually occurs in sun-damaged skin on the head and neck of elderly patients. Depending on the anatomical site and its size treatment of LM can be problematic and usually includes surgical excision or radiotherapy. Recent reports indicate that topical imiquimod may be an effective treatment. However, no data on the underlying immune response in the skin during treatment of LM with topical imiquimod are available so far. We report a 62-year-old caucasian woman with a histologically verified LM which was successfully treated with topical imiquimod 5% cream. Skin biopsy specimens were obtained before, during (at week 10) and 4 weeks after cessation of topical treatment with imiquimod 5% cream. Histological and immunohistochemical examination was performed in order to detect residual atypical melanocytes and to characterize the inflammatory infiltrate. A complete clinical and histological clearance of the skin lesion was achieved, with no recurrence up to 9 months after the end of treatment. During topical application of imiquimod 5% cream a depletion of epidermal and dermal CD1a+ dendritic cells was observed. The inflammatory infiltrate consisted of CD68+ macrophages and mainly of CD3+ T cells with a slight predominance of CD8+ T cells. An enhanced expression of granzyme B and TIA-1 was also noted particularly in the epidermis and near the dermoepidermal junction. In conclusion, our data indicate that imiquimod 5% cream induces a cytotoxic T-cell-mediated immune response in situ which may account for the complete destruction of the malignant melanocytes in LM. Further clinical trials and longer follow-up periods on the use of imiquimod for LM are warranted.
Aminoquinolines↗
Eosinophils and atopic dermatitis.
In spite of the progress regarding the description of immunological phenomena associated with atopic dermatitis (AD), the pathogenesis of this disease still remains unclear. The presence of eosinophils in the inflammatory infiltrate of AD has long been established. Eosinophil numbers as well as eosinophil granule protein levels in peripheral blood are elevated in most AD patients and appear to correlate with disease activity. Moreover, eosinophil granule proteins, which possess cytotoxic activity, are deposited in the skin lesions. These observations indicate a role of eosinophils in the pathogenesis of AD. Furthermore, AD is associated with increased production of T helper 2 cytokines including interleukin (IL)-5, which specifically acts on eosinophils, resulting in accelerated eosinophilopoiesis, chemotaxis, cell activation, and delayed apoptosis. Therefore, IL-5 is an interesting target for experimental therapy in this inflammatory disorder of the skin. Such studies might result in new insights into the pathogenetic role of eosinophils in AD.
Chemokine CCL11↗
The prevalence of positive reactions in the atopy patch test with aeroallergens and food allergens in subjects with atopic eczema: a European multicenter study.
BACKGROUND: The atopy patch test (APT) was proposed to evaluate IgE-mediated sensitizations in patients with atopic eczema (AE). OBJECTIVE: The prevalence and agreement with clinical history and specific IgE (sIgE) of positive APT reactions was investigated in six European countries using a standardized method. METHODS: A total of 314 patients with AE in remission were tested in 12 study centers on clinically uninvolved, non-abraded back skin with 200 index of reactivity (IR)/g of house dust mite Dermatophagoides pteronyssinus, cat dander, grass, and birch pollen allergen extracts with defined major allergen contents in petrolatum. Extracts of egg white, celery and wheat flour with defined protein content were also patch tested. APT values were evaluated at 24, 48, and 72 h according to the European Task Force on Atopic Dermatitis (ETFAD) guidelines. In addition, skin-prick test (SPT) and sIgE and a detailed history on allergen-induced eczema flares were obtained. RESULTS: Previous eczema flares, after contact with specific allergens, were reported in 1% (celery) to 34% (D. pteronyssinus) of patients. The frequency of clear-cut positive APT reactions ranged from 39% with D. pteronyssinus to 9% with celery. All ETFAD intensities occured after 48 and 72 h. Positive SPT (16-57%) and elevated sIgE (19-59%) results were more frequent. Clear-cut positive APT with all SPT and sIgE testing negative was seen in 7% of the patients, whereas a positive APT without SPT or sIgE for the respective allergen was seen in 17% of the patients. APT, SPT and sIgE results showed significant agreement with history for grass pollen and egg white (two-sided Pr > /Z/ < or = 0.01). In addition, SPT and sIgE showed significant agreement with history for the other aeroallergens. With regard to clinical history, the APT had a higher specificity (64-91% depending on the allergen) than SPT (50-85%) or sIgE (52-85%). Positive APT were associated with longer duration of eczema flares and showed regional differences. In 10 non-atopic controls, no positive APT reaction was seen. CONCLUSION: Aeroallergens and food allergens are able to elicit eczematous skin reactions after epicutaneous application. As no gold standard for aeroallergen provocation in AE exists, the relevance of aeroallergens for AE flares may be evaluated by APT in addition to SPT and sIgE. The data may contribute to the international standardization of the APT.
Adolescent↗
Progressive respiratory failure in paraneoplastic pemphigus associated with chronic lymphocytic leukemia.
A 70-year-old Caucasian man with chronic lymphocytic leukemia suffered from widespread, histologically proven cutaneous lichen planus responding to topical corticosteroids. 2 years later, he presented with painful erosive stomatitis and increasing dyspnea. Histology, direct and indirect immunofluorescence were diagnostic for paraneoplastic pemphigus. A full diagnostic workup could not disclose the cause of the progressive respiratory insufficiency. Despite aggressive treatment of the lymphocytic leukemia and the paraneoplastic pemphigus, the patient died 3 months after diagnosis. Paraneoplastic pemphigus may lead to pulmonary failure which is refractory to treatment and has a fatal outcome.
Aged↗
Acute generalized exanthematic pustulosis: a case and an overview of side effects affecting the skin caused by celecoxib and other COX-2 inhibitors reported so far.
A 55-year-old woman who was treated for periarthritis humeroscapularis with celecoxib (Celebrex) developed a generalized pustular exanthema on the head and upper trunk, accompanied by fever, leukocytosis and increased erythrocyte sedimentation rate. The histological findings were subcorneal pustules, necrotic keratinocytes, edema in the upper dermis and polymorphic perivascular infiltrates. Four days after stopping celecoxib, the pustules disappeared without any treatment. Four weeks after disappearance of the skin lesions, celecoxib demonstrated a positive lymphocyte stimulation test. In this article, we present to our knowledge the first case of acute generalized exanthematic pustulosis caused by celecoxib, and we give an overview of the side effects affecting the skin caused by celecoxib and other cyclooxygenase type 2 inhibitors reported so far.
Arm↗
[Pruritus sine marteria. Pathophysiology, diagnostic assessment and therapy].
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Dermatologic Agents↗
Peripheral blood mononuclear cells from IgE- and non-IgE-associated allergic atopic eczema/dermatitis syndrome (AEDS) demonstrate increased capacity of generating interleukin-13 but differ in their potential of synthesizing interferon-gamma.
BACKGROUND: A subgroup of patients with allergic atopic eczema/dermatitis syndrome (AEDS) are known to have normal total and specific IgE levels and negative skin prick tests towards common environmental allergens. This form of the disease has been termed non-IgE-associated allergic AEDS. Although allergic mechanisms appear to be important, the pathogenesis of both IgE- and non-IgE-associated forms of the disease is unknown. METHODS: We have compared the cytokine production pattern of peripheral blood mononuclear cells (PBMC) from IgE-associated AEDS, non-IgE-associated AEDS, and normal control individuals. PBMC were stimulated with anti-CD3 and/or anti-CD28 monoclonal antibodies (mAb) and cytokine production was measured by immunoassays in supernatants of 24-h cultures. RESULTS: Compared to healthy subjects and non-IgE-associated AEDS patients, stimulated PBMC from IgE-associated AEDS patients produced less interferon (IFN)-gamma. However, stimulated PBMC from both IgE-associated AEDS and non-IgE-associated AEDS patients produced more interleukin (IL)-13 than PBMC from control individuals. Moreover, IL-5 production was significantly increased in non-IgE-associated AEDS but not in IgE-associated AEDS patients. CONCLUSIONS: The underlying mechanism leading to increased differentiation of T helper (Th) 2 cells may involve a deficient capacity in producing IFN-gamma in IgE-associated AEDS but not in non-IgE-associated AEDS patients. IL-13 may be a key cytokine in the pathogenesis of both allergic forms of AEDS.
Adult↗
Photodynamic therapy: when and why?
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Carcinoma↗
[The University Dermatology Clinic in Bern].
The history of the university dermatology clinic in Bern can be followed back into the 13th century to the founding of the Siechenhaus (hospice for incurable patients) in 1283. The hospice was moved in 1491 to the Breitfeld before the gates of the city, where over the next four centuries it expanded greatly and served patients with leprosy and later syphilis and other skin diseases. In the beginning of the 19th century teaching in dermato-venerology was carried out here. In 1891/82 one of the earliest dermatology clinics was established, as a professorship was established and the clinic moved to a new building on the grounds of the Inselspital, the university hospital. Through the efforts of the first chairmen, E. Lesser and J. Jadassohn, as well as their successors, dermato-venerology has remained well-established in Bern. We review the important dates, individuals and institutions and their role on the long development of dermato-venerology in Bern from its early roots until today.
Dermatology↗