Short- and long-term effects of two emollients on itching and skin restoration in xerotic eczema.

Pruritus is associated with various skin diseases, dry skin, and with it an impaired skin barrier function. The study objective was to investigate short-term and long-term effects of two emollients on symptoms and skin barrier functions in xerotic eczema. Randomized, double-blind, study enrolling females/males, with bilateral itching. Two emollients, containing lactic acid and refined almond oil with/without polidocanol were administered on left versus right body sides. Itching severity, skin moisture, lipid content, and pH were assessed on Day 1, within 30-120 min after first administration, and on Days 7 and 14, and compared with baseline assessments. Severity of itching decreased 30 min after first administration of both emollients compared with baseline (p < .0001) and reached a maximum reduction of 63% (p < .0001) and 69% (p < .0001) on Day 14. Skin moisture and lipid content increased after first application, and further ameliorated within 14 days of treatment (p < .0001). Both emollients were tolerated well, and only a few adverse events were reported. This study confirmed the clinical efficacy of the two study emollients to substantially reduce itching already after first administration, and restore skin barrier integrity and thus should be considered as therapeutic approach for xerotic eczema.

Gamma-linolenic acid levels correlate with clinical efficacy of evening primrose oil in patients with atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) has been related to a deficiency of delta-6-desaturase, an enzyme responsible for the conversion of linoleic acid to gamma-linolenic acid (GLA). Evening primrose oil (EPO) contains high amounts of GLA. Therefore, this study investigated whether EPO supplementation results in an increase in plasma GLA and its metabolite dihomo-gamma-linolenic acid (DGLA) correlating with clinical improvement of AD, assessed by the SCORing Atopic Dermatitis (SCORAD) index. METHODS: The open study included 21 patients with AD. EPO (4-6 g) was administered daily for 12 weeks. Before treatment, and 4 and 12 weeks after initiation of EPO supplementation, objective SCORAD was assessed and plasma concentrations of GLA and DGLA were determined by gas chromatography. RESULTS: A significant increase in plasma GLA and DGLA levels and a decrease in the objective SCORAD were observed 4 and 12 weeks after initiation of EPO treatment. In the per-protocol population (n = 14), a significant inverse correlation between the changes in plasma GLA levels and SCORAD was found (P = 0.008). CONCLUSION: The clinical disease activity under EPO treatment correlates with the individual increase in plasma GLA levels. Thus, the results of this pilot study indicate that an increase in plasma GLA might be used as predictive parameter for responsiveness of AD to EPO therapy.

Molecular diagnostics of parapox virus infections.

BACKGROUND: The diagnosis of parapox virus infections relies primarily on a history of contact with infected animals. The clinical presentation is usually a non-specific necrotic ulcer. The histology may also be non-specific, especially with older lesions. Negative-staining electron microscopy (EM) is a fast and reliable diagnostic tool, but is not widely available. Serological tests and the time-consuming viral culture are also rarely used in Europe. PATIENTS AND METHODS: The diagnostic procedure in two patients with ecthyma contagiosum and milker's nodule using polymerase chain reaction specific for orthopox, parapox and Orf virus is explained. Diagnostics included bacterial culture, viral culture, histology and EM. In addition to these, a polymerase chain reaction (PCR) was performed in both cases. RESULTS: The patient with ecthyma contagiosum was negative for ortho-, parapox-, and orf-virus on PCR, whereas the patient with milker's nodule had a PCR positive for parapoxvirus. CONCLUSIONS: PCR is a simple, fast, and standardized method of diagnosis that can distinguish between the subgroups of parapoxviruses. A diagnosis can be made even in cases of ambiguous history or unspecific clinical presentation. The method is limited by the necessity to sample native material or to use neutrally buffered formalin in case of PCR from paraffin material.

[Effectiveness of a classical homeopathic treatment in atopic eczema. A randomised placebo-controlled double-blind clinical trial]. / Wirksamkeit einer klassisch-homöopathischen Therapie bei atopischem Ekzem. Eine randomisierte, placebokontrollierte Doppelblindstudie.

BACKGROUND: Atopic dermatitis (atopic eczema) is one of those diseases where homeopaths claim to have good success although this has never been proven by rigorously controlled trials. METHODS: Single-centre, randomised, double-blind clinical trial comparing homeopathic remedies with placebo in young adults (age 18-35) with atopic dermatitis. Homeopathic remedies were individually administered according to the rules of classical homeopathy. After an untreated baseline period of 4 weeks, all patients were treated and monitored for 32 weeks. Throughout the study, co-medication was allowed only with indifferent emollients. The main outcome parameter was disease severity as assessed by Costa and Saurat's multi-parameter atopic dermatitis score (MP-score). RESULTS: 744 patients were screened out of which 24 (10 verum, 14 placebo) were randomised and analysed. Treatment groups were balanced in most baseline parameters but MP-scores were significantly higher in verum patients (p = 0.034, t-test). 10 patients (5 per group) dropped out of the study, mainly because the treatment was perceived as ineffective and co-medication was needed. The MP-score decreased from 54.5 +/- 11.0 to 40.7 +/- 12.5 in the verum group and from 45.9 +/- 7.6 to 32.7 +/- 21.8 in the placebo group, resulting in a non-significant group difference of 5.6 in favour of placebo (CI: -9.0 to 20.2; p = 0.46; ANCOVA). No secondary parameter (quality of life, coping, global assessments of treatment success) showed significant differences between groups (all p > 0.15). CONCLUSIONS: In this study, individualised homeopathic remedies did not prove to be superior to placebo in atopic dermatitis. Yet, generalisability of results is limited due to the small number of patients and the high percentage of ineligible patients.

Differential expression of pyloric atresia in junctional epidermolysis bullosa with ITGB4 mutations suggests that pyloric atresia is due to factors other than the mutations and not predictive of a poor outcome: three novel mutations and a review of the literature.

Junctional epidermolysis bullosa with pyloric atresia (JEB-PA) is an autosomal recessive blistering disease including lethal and non-lethal variants due to mutations in ITGB4 and ITGA6. It is unclear whether PA is caused directly by the mutations in these genes or by other factors. Skin biopsies from patients with JEB were processed for immunofluorescence mapping. When staining for integrin beta4 or alpha6 was absent or reduced, ITGB4 was screened for mutations. A review of known mutations of ITGB4 and the phenotypes of patients with JEB-PA was undertaken. Three novel ITGB4 mutations were identified in 3 families with JEB-PA: 2 splice-site and one insertion mutation. Two families with lethal phenotypes (EB-050 and EB-049) were due to combinations of premature termination codons and missense mutations (658delC/R252C and 3903dupC/G273D, respectively). The third family EB-013 has 2 JEB affected siblings; a brother with PA and a sister without PA. Both were homo notzygous for ITGB4 264G>A/3111-1G>A. Two cases had no gastrointestinal symptoms or signs of PA. PA is an inconstant feature of the subtype of epidermolysis bullosa known as JEB-PA. It is most likely that multiple factors influence the development of PA and its presence is not predictive of a poor outcome. It is possible that institutions that do not routinely screen immunofluore notscence mapping for integrin alpha6beta4 staining in the absence of PA are missing this form of epidermolysis bullosa.

The interleukin-13 production by peripheral blood T cells from atopic dermatitis patients does not require CD2 costimulation.

BACKGROUND: Although allergic mechanisms appear to be important, the pathogenesis of both extrinsic and intrinsic forms of atopic dermatitis (AD) is unknown. METHODS: We compared the cytokine production of peripheral blood mononuclear cells of extrinsic AD (EAD) and intrinsic AD (IAD) patients and normal control individuals after stimulation with anti-CD3 and/or anti-CD28 monoclonal antibodies (mAbs) in the presence or absence of anti-CD2-blocking mAb. The cytokine production was measured by immunoassays in supernatants of 24-hour cultures. RESULTS: EAD patients showed a decreased capacity to synthesize interferon gamma and granulocyte-macrophage colony-stimulating factor upon anti-CD3 mAb stimulation as compared with IAD patients. Both EAD and IAD patients demonstrated an increased production of interleukin (IL)-5 and IL-13. As expected, interferon gamma, granulocyte-macrophage colony-stimulating factor, and IL-5 levels were reduced in the presence of anti-CD2-blocking mAbs. CD28 costimulation restored the release in cultures with anti-CD2 mAbs added, suggesting that CD2 and CD28 have redundant functions in T cell activation and subsequent cytokine production. Strikingly, the IL-13 production was not blocked by anti-CD2 mAbs and also not increased by agonistic anti-CD28 mAb, in particular within the EAD patient group. CONCLUSION: The signalling pathway initiated by the T cell receptor complex leading to increased IL-13 production in AD patients appears to be highly sensitive and is largely independent on CD2 costimulatory signals.

Limitations of the immunocytochemical detection of isolated tumor cells in frozen samples of bone marrow obtained from melanoma patients.

We report on a case of a 70-year-old woman with an ocular melanoma, which was diagnosed and treated 14 years ago. The patient was referred to the hospital with a suspected lymphoma. Cytological examination of bone marrow proved a marked infiltration with melanoma cells. Because detection of isolated tumor cells in the bone marrow of patients with various types of tumors was shown to be of prognostic significance and since current tumor-staging techniques are unable to detect single disseminated tumor cells or small aggregates of tumor cells, which might be the seed for subsequent metastatic relapse, we therefore evaluated the feasibility of immunocytochemical screening of bone marrow aspirates of 36 melanoma patients in different clinical stages using three monoclonal antibodies against melanoma-associated antigens in comparison with 43 non-melanoma control patients. Two of these antibodies (HMB45 and NKI-beteb) are directed against the melanoma antigen gp100/pmel17, whereas the third one (TA99) recognizes gp75/Tyrosinase-related protein 1 (TRP-1). None of the patients demonstrated a macroscopic bone marrow infiltration as was present in our patient with metastatic ocular melanoma. Seven (20.6%) of the 34 eligible melanoma patients presented with cells in the bone marrow positive for one or more of the above-mentioned melanosomal markers. Four of the positive patients were clinically free of tumors by the time of puncture, whereas the remaining 3 patients showed overt metastases in the subcutaneous fat (2 patients) and the brain (1 patient). On the other hand, 20 (66%) of the 29 patients with negative bone marrow findings also presented with clinical advanced disease with overt metastasis in the skin, lymph node, spleen, liver, lung, bone and brain. In conclusion, immunocytochemical screening of bone marrow samples is a feasible procedure that allows the detection of micrometastatic tumor cells in a subset of melanoma patients. Massive invasion of bone marrow with melanoma cells is a rare event even in far-advanced metastatic stages and no clear correlation between tumor load and bone marrow infiltration could be established.

Orange-induced skin lesions in patients with atopic eczema: evidence for a non-IgE-mediated mechanism.

Oranges are suspected of inducing adverse skin reactions in patients with atopic eczema. We studied 21 adult patients with atopic eczema and a history of adverse reactions to oranges and 10 patients without. A dietary history, skin tests, serum IgE and oral provocation tests with oranges were obtained. Severity of eczema was monitored by SCORAD, and serum tryptase, eosinophil cationic protein and urinary methylhistamine were measured. No allergic reactions were found to orange in skin prick or patch tests. However, 23 patients (74%) had specific serum IgE to orange. Oral provocation testing resulted in pruritic eczematous or maculopapular skin lesions predominantly at the predilection sites in 16 patients (52%). The SCORAD increased significantly in patients positive to the oral provocation test (p <0.05). Specific IgE to orange did not correlate with the clinical outcome of the oral provocation test. No significant changes were found in serum mast cell tryptase, eosinophil cationic protein or in urinary methylhistamine excretion. The negative results in the skin tests and a lack of correlation between specific IgE and oral provocation tests indicate that non-IgE-mediated mechanisms are involved in cutaneous adverse reactions to oranges in patients with atopic eczema.

Occupational protein contact dermatitis from spices in a butcher: a new presentation of the mugwort-spice syndrome.

Protein contact dermatitis to meat is well known in butchers; spices are another source of potential contact allergy and usually are not recognized. We present a first case of contact-dermatitis to spice mix in a 39-year-old-butcher. The patient underwent skin prick testing (SPT) with standard allergens (ALK) and different meat and spice extracts (Stallergènes), scratch-patch testing with spice mix containing glutamate, paprika and other spices. Specific serum-IgE was measured with CAP-FEIA. SPT only showed an immediate-type sensitization to mugwort (+ +), as well as different spices (paprika +, curry +, cumin +) and camomile (+ + +). Scratch-patch tests were negative for different meat, but strongly positive for spice mix (+ + +) after 30 min (wheal and flare) and (+ +) after 48 h (infiltration and vesiculation). Two healthy controls were tested negative for spice mix used from that patient (scratch-patch). Specific IgE was slightly elevated for paprika 0.47 kU/L (CAP class 1), anise 0.43 kU/L, curry 0.36 kU/L and mugwort 3.83 kU/L. Sx1 atopy-multiscreen was 3.8 kU/L due to a sensitization to mugwort alone. The tests performed demonstrate an IgE-mediated contact allergy to spices but also a delayed type allergy to spice mix as a manifestation of the mugwort-spice syndrome in this individual. When testing for occupational dermatitis in butchers, protein contact allergy to spices must also be taken into consideration.