An improved mouse model of atopic dermatitis and suppression of skin lesions by an inhibitor of Tec family kinases.

Background: Atopic dermatitis is a chronic or chronically relapsing, pruritic inflammatory skin disease. The incidence of atopic dermatitis has dramatically increased during the past three decades in industrialized countries. We attempted to develop an improved method to induce an animal model of atopic dermatitis and to use it to evaluate the efficacy of a Tec family kinase inhibitor. Methods: We treated dermatitis-prone inbred mice, NC/Nga, by repetitive epicutaneous applications of a house dust mite allergen and staphylococcal enterotoxin B to induce atopic dermatitis-like skin lesions. Results: We established a highly efficient protocol to induce skin lesions in NC/Nga mice, which were histologically and immunologically similar to human atopic dermatitis. Similar to human patients, serum IgE levels were increased in dermatitis-induced mice. Consistent with the proposed roles of infiltrated immune cells in the pathogenesis of human atopic dermatitis, skin lesions were treatable with terreic acid, an inhibitor of Tec family kinases, as well as dexamethasone. Conclusions: We established a highly efficient, highly reproducible protocol to induce skin lesions in NC/Nga mice and successfully applied it to show the efficacy of terreic acid in treating skin lesions. This mouse model of atopic dermatitis will be useful to study the pathogenetic processes of atopic dermatitis and to evaluate the efficacy of drug candidates.     

A septic pulmonary embolism associated with right-sided infective endocarditis and a ventricular septal defect in a patient with atopic dermatitis

A 30-year-old woman was admitted to our hospital with high fever and chest pain. She had a ventricular septal defect, but was asymptomatic and had not undergone surgical repair. She also had had atopic dermatitis since childhood that had not been adequately treated. Chest computed tomography showed multiple peripheral nodules and infiltrates in both lungs. A transthoracic echocardiogram detected vegetation on the wall of the right ventricle, and Staphylococcus aureus was cultured from a peripheral blood sample. She was diagnosed as having a septic pulmonary embolism associated with right-sided infective endocarditis caused by S. aureus. She was treated with Cefazolin, resulting in gradual improvement of laboratory and chest radiographic findings. Recent studies have revealed that atopic dermatitis is one of the risk factors for infective endocarditis. In this case, uncontrolled atopic dermatitis might have caused the right-sided infective endocarditis.     

Nosocomial dermatitis and pruritus caused by pigeon mite infestation

We report an outbreak of pigeon mite infestation involving two patients, two nurses, and one physician on a medical ward in a municipal hospital. The index patient developed a diffuse, pruritic erythematous maculopapular rash on his trunk and extremities. Dermanyssus gallinae, a nonburrowing, blood-sucking avian mite was identified on the patient and his bedding. A second patient who complained of scalp pruritus had mites present on her pillow and bed linen. The intern taking care of both patients, and two nurses who had contact with these patients, had mite infestation. Pigeons roosting on the air conditioners and near the doors connecting the patients' rooms to a sunporch were the source of the mites. The outbreak abated after control measures were instituted that prevented pigeons from roosting on the porch. This outbreak illustrates an unusual cause of nosocomial pruritic dermatitis that may be misdiagnosed as scabies or pediculosis. Physicians and health care personnel working in metropolitan areas are alerted to mites as a cause of pruritic dermatitis that may be chronic, recurrent, or unresponsive to ectoparasiticides.     

Atopic dermatitis as a risk factor for acute native valve endocarditis

Colonization of Staphylococcus aureus is commonly observed in skin lesions of atopic dermatitis (AD) patients, and scratching of the pruritic lesions may lead to reiterative bacteremia. It is possible that acute native valve endocarditis may develop in a patient with uncontrolled AD; the latter condition may be a risk factor for the former. We report two cases of acute aortic and/or mitral valve endocarditis complicated with recurrent cutaneous infections caused by severe AD. The patients underwent successful surgical treatment of the heart lesions, plus intensive postoperative antibiotics and skin treatment for AD.     

Infective endocarditis with a huge mitral vegetation related to atopic dermatitis and high serum level of infection-related antiphospholipid antibody: a case report

A 24-year-old woman with atopic dermatitis was admitted to our hospital with fever. Echocardiography showed a huge vegetation attached to the posterior mitral commissure without mitral valve dysfunction. Blood culture identified methicillin-sensitive Staphylococcus aureus. The serum level of antiphospholipid antibody was elevated. A splenic infarction occurred on the second hospital day. Surgery to resect the residual mobile vegetation was performed uneventfully on the 6th hospital day. The postoperative course was uneventful, and the patient was discharged after 4 weeks of antibiotic therapy. Preservation of the mitral valve is rare in the face of virulent Staphylococcus infection and the presence of a huge mobile vegetation. These findings were apparently related to the high serum level of infection-related antiphospholipid antibody and atopic dermatitis.     

Occurrence of a house-infesting Tropical rat mite (Ornithonyssus bacoti) on murides and human beings

In Germany there is little information available about the distribution of the Tropical rat mite (Ornithonyssus bacoti) in rodents. A few case reports show that this haematophagous mite species may also cause dermatitis in man. All developmental stages are exclusively bloodfeeder. Three children (4, 11 and 15 years old) of a family and a 23-year-old medical student were attacked by the Tropical rat mite. Prior to the consultation of our institution, the patients' conditions had been diagnosed as allergic dermatitis of unclear origin and treated by several antiphlogistic agents, however without success. The conclusive diagnosis, Tropical rat mite dermatitis, was based on the identification of the arthropod Ornithonyssus bacoti in the flats of the patients (husbandry of gerbils, etc.). The diagnosis of a Rat mite dermatitis requires the detection of the parasite, which is more likely to be found in the environment of its host than on the hosts' skin itself.     

A case of atopic dermatitis and erythema multiforme

We report a case of a two-year-old boy with atopic dermatitis treated with antibiotics for pharyngitis and acute otitis media and subsequently developed targetoid and ulcerated blister mucocutaneous lesions. Diagnostic workup revealed eczema herpeticum and HSV viremia. To our knowledge, this is the first reported case of a patient with atopic dermatitis presenting with erythema multiforme likely secondary to eczema herpeticum and HSV viremia.     

Prevalence of atopic disorders in rheumatic diseases

Objectives

The aim of this study was to assess the point prevalences of hay fever, asthma, and atopic dermatitis in OA, RA, and AS, and to compare with healthy controls.

Methods

A total of 935 patients and healthy controls were included. Demographic and clinical features were recorded, and a questionnaire assessing the existence of atopic disorders like asthma, hay fever, and atopic dermatitis in all groups was applied. “Either atopy” implied that an individual was either diagnosed with or had symptoms of one or more of these disorders, such as asthma, hay fever, or atopic dermatitis.

Results

When compared to the controls, only patients with AS had an increased risk for hay fever (OR 1.52, 95 % CI 1.00–2.41). Patients with RA had increased risks for hay fever, atopic dermatitis, and either atopy compared to the patients with OA (2.14, 95 % CI 1.18–3.89; 1.77, 95 % CI 1.00–3.18; and 3.45, 95 % CI 1.10–10.87, respectively). Steroid use had no effect on the prevalence of atopic disorders in patients with RA.

Conclusions

Patients with OA, RA, and AS seem to have similar risks for asthma, atopic dermatitis, and either atopy to healthy controls. However, the prevalence of hay fever may increase in AS. Patients with RA have a higher risk of atopy than patients with OA.     

An idiopathic skin eruption resembling a butterfly rash in a septic patient with disseminated intravascular coagulation following bone marrow transplantation.

A 31-year-old man who underwent chemotherapy and bone marrow transplantation to treat acute myeloblastic leukemia was admitted to our department complaining of high fever and hypotension. His physical examination revealed warm shock state, eruptions resembling that seen in systemic lupus erythematosus on his face and cyanosis in his fingers. We diagnosed septic shock and idiopathic skin eruption on his face. Following treatment with blood transfusion, anticoagulant, antibiotics, respirator and continuous arteriovenous hemofiltration and dialysis, the patient's condition gradually improved. The eruptions on his face first observed at admission progressed with a worsening of his disseminated intravascular coagulation (DIC), and subsided with an improvement in his DIC. A biopsy of the eruption was taken and pathological findings of the eruption revealed multiple micro-fibrin depositions of the dermis. The skin necrosis in purpura fulminans often begins in the distal extremities. But our patient developed this uncommon skin eruption on his face. Patients with an idiopathic skin eruption resembling a butterfly rash in a septic patient should be considered to complicate DIC as in the present case.     

A case of disseminated DLE complicated by atopic dermatitis and Sjögren’s syndrome: link between hypohidrosis and skin manifestations

We report an unusual case of disseminated discoid lupus erythematosus (DLE) complicated by pre-existing atopic dermatitis (AD) and late-onset Sjögren’s syndrome (SS). Disseminated DLE lesions were sparse on the expected sites for AD, such as the medial region of the extremities or v-neck area. The patient fulfilled the diagnostic criteria for AD and SS but not for systemic lupus erythematosus. Histopathological analysis of the crusted erythematous lesions revealed typical DLE with few FoxP3⁺ cells and a moderate number of IL-17⁺ cells. A quantitative sweating test showed impaired sweating of both lesional and non-lesional skin due to underlying hypohidrosis that was related to AD and SS. This finding suggests that dissemination of DLE was triggered by scratching and a Köbner phenomenon-like effect related to hypohidrotic and xerotic skin. To the best of our knowledge, this is the first reported case of disseminated DLE complicated by AD and SS.     

Etiologic implication of foods in atopic dermatitis: evidence against

Atopic dermatitis is a typical chronic inflammatory skin disease that usually occurs in individuals with a personal or family history of atopy. Children with atopic dermatitis frequently present IgE-mediated food sensitization, the most commonly involved foods being egg and cow's milk. However, controversy currently surrounds whether food allergy is an etiological factor in atopic dermatitis or whether it is simply an associated factor, accompanying this disease as one more expression of the patient's atopic predisposition. Approximately 40 % of neonates and small children with moderate-to-severe atopic dermatitis present food allergy confirmed by double-blind provocation tests but this allergy does not seem to be the cause of dermatitis since in many cases onset occurs before the food responsible for allergic sensitization is introduced into the newborn's diet.Studies of double-blind provocation tests with food in patients with atopic dermatitis demonstrate mainly immediate reactions compatible with an IgE-mediated allergy. These reactions occur between 5 minutes and 2 hours and present mainly cutaneous symptoms (pruritus, erythema, morbilliform exanthema, wheals) and to a lesser extent, digestive manifestations (nausea, vomiting, abdominal pain, diarrhea), as well as respiratory symptoms (wheezing, nasal congestion, sneezing, coughing). However, these reactions do not indicate the development of dermatitis.Some authors believe that responses to the food in provocation tests may also be delayed, appearing mainly in the following 48 hours, and clinically manifested as exacerbation of dermatitis. However, delayed symptoms are difficult to diagnose and attributing these symptoms to a particular foodstuff may not be possible.Delayed reactions have been attributed to a non-IgE-mediated immunological mechanism and patch tests with food have been proposed for their diagnosis. In our experience and in that of other authors, the results of patch tests with cow's milk do not seem very specific and could be due, at least in part, to the irritant effect of these patches on the reactive skin of children with atopic dermatitis.The involvement of foods in atopic dermatitis will always be difficult to demonstrate given that an exclusion diet is not usually required for its resolution. Food is just one among several possible exacerbating factors and consequently identification of its precise role in the course of the disease is difficult. Further double-blind prospective studies are required to demonstrate the effectiveness of exclusion diets in the treatment of atopic dermatitis.Apart from the controversy surrounding the etiological role of foods, the most important point in atopic dermatitis is to understand that the child is atopic, that is, predisposed to developing sensitivity to environmental allergens; in the first few years of life to foods and subsequently to aeroallergens. Consequently, possible allergic sensitization to foods should be evaluated in children with atopic dermatitis to avoid allergic reactions and to prevent the possible development of allergic respiratory disease later in life.     

Importance of genetic factors in the etiology of atopic dermatitis: a twin study.

The susceptibility to develop atopic dermatitis can be attributed both to genetic and environmental causes. We estimated the relative impact of genetic and environmental factors in the etiology of atopic dermatitis in a population-based sample of twins. From the birth cohorts of 1953-1982 who were enrolled in The Danish Twin Registry, a total of 11,515 twin pairs were identified in a nationwide questionnaire survey. Subjects were classified as atopic dermatitis cases when responding affirmatively to the question, "Do you have, or have you ever had, eczema in the folds of your elbows or knees?" Latent factor models of genetic and environmental influences were fitted to the observed data using maximum likelihood methods. The overall lifetime prevalence of atopic dermatitis was 7.3%. A cotwin of an affected identical twin had a sevenfold increased risk of atopic dermatitis compared with a threefold increased risk among cotwins of an affected fraternal twin, relative to the general population. Genes accounted for 82% and nonshared environmental factors accounted for 18% of the individual susceptibility to develop atopic dermatitis. The same genes contributed to the susceptibility to atopic dermatitis both in male and female patients (p = 0.98). The estimates were adjusted for age. The susceptibility to develop atopic dermatitis is attributable to mainly genetic differences between people. However, differences in environmental exposures also are of importance.     

"Centripetal flagellate erythema": a cutaneous manifestation associated with dermatomyositis

We describe 3 patients with dermatomyositis who presented with flagellate erythema. This cutaneous eruption is characterized by erythematous linear lesions on the trunk and proximal extremities. Histologic examination of this eruption in one of our cases revealed an interface dermatitis. Review of the literature and records of 183 patients with connective tissue diseases from our institution has shown that this peculiar eruption has been reported only in dermatomyositis. Because of the location of this eruption, we encourage the use of the term "centripetal flagellate erythema" to distinguish this entity from other linear eruptions seen in patients with connective tissue diseases.     

Exacerbating factors and disease burden in patients with atopic dermatitis

The number of patients with atopic dermatitis is on the rise worldwide, and Japan is no exception. According to recent estimates of the percentage of patients with atopic dermatitis in Japan by age, the majority of patients are between 20 and 44 years old. Because the peak age of onset of atopic dermatitis is during infancy, many patients may experience prolonged symptoms from infancy to adulthood. A prolonged clinical course also increases the burden of atopic dermatitis on affected patients. Decreased productivity due to work disruptions, reduced daily activity, higher direct medical costs, fatigue, and daytime sleepiness due to sleep disturbances are typical burdens on patients with atopic dermatitis. In order to reduce these burdens, it is necessary to shorten its clinical course and achieve long-term control without relying on medications, possibly by using avoidance or coping measures of aggravating factors. Typical aggravating factors of atopic dermatitis include irritant dermatitis, food allergy in children, sweating, and psychological stress in adults. Food allergy places a heavy burden on the quality of life of affected patients and their families. The effectiveness of educational interventions for sweating and psychological stress is unclear. We must also evaluate the economic burden and cost-effectiveness of interventions on the patient as aggravating factors to be addressed.     

Lupus erythematosus tumidus in Japan: a case report and a review of the literature

We report here the case of a 48-year-old Japanese woman showing plaque-forming scattered indurative papules on her face, buttock and extremities. Histological examination revealed a large amount of interstitial mucin deposition, and negative direct immunofluorescence was observed. The provocative phototesting reproduced the skin lesion, and the patient was diagnosed with lupus erythematosus tumidus (LET). A review of ten LET cases previously reported in Japan revealed that all of these cases had clinicopathological features similar to those reported for European cases, although not all of the former fully satisfied the European criteria.     

Erythema multiforme: As a complication of allergen-specific immunotherapy

Here we present a 25-year-old female patient admitted with a complaint of blistering lesions on her face, neck, chest and extremities appearing after the first dosis of specific immunotherapy and diagnosed as erythema multiforme. To our knowledge, there are no papers in the literature reporting erythema multiforme due to specific immunotherapy.     

Looking for immunotolerance: a case of allergy to baker's yeast (Saccharomyces cerevisiae)

We describe one case of baker's yeast true allergy in a boy with previously diagnosed mite-allergy and atopic dermatitis. At the age of 6, being atopic dermatitis and rhinitis well controlled by drugs, he began to experience generalized urticaria and asthma after eating pizza and bread, but only fresh from the oven. The diagnostic workup revealed single sensitization to baker's yeast (Saccharomyces cerevisiae), and a severe systemic reaction also occurred during the prick-by-prick procedure. After discussing with parents, no special dietary restriction was suggested but the use of autoinjectable adrenaline and on demand salbutamol. A diary of symptoms was recorded by means of a visual-analog scale. During the subsequent 2 years, the severity of symptoms was progressively reduced, and presently urticaria has disappeared. Only cough persists, invariantly after eating just-baked and yeast-containing foods. If bread, pizza and cakes are ate more than one hour after preparation, no symptom occur at all. Baker's yeast is a common component of everyday diet and it usually acts as an allergen only by the inhalatory route. We speculate that the continuous exposure to saccharomyces in foods may have lead to an immunotolerance with a progressive reduction of symptoms, whereas why the allergens is active only in ready-baked foods remains unexplained.     

Association of atopy, asthma, allergic rhinoconjunctivitis, atopic dermatitis and intestinal helminth infections in Cuban children

Objective To examine the relationship of past and current intestinal helminth infections with asthma, allergic rhinoconjunctivitis, atopic dermatitis and atopy. Methods Cross‐sectional study of 1320 children aged 4–14 years from two Cuban municipalities. Helminth infections were determined by stool examination and parental questionnaire. Asthma, rhinoconjunctivitis and atopic dermatitis were diagnosed by International Study of Asthma and Allergies in Childhood questionnaire, asthma additionally by spirometry, atopy by skin prick testing. Results Questionnaire‐based frequencies were 21% for asthma, 14% for allergic rhinoconjunctivitis and 8% for atopic dermatitis. According to spirometry, 4% had asthma; 20% had a positive skin prick test. A history of infection for Enterobius vermicularis was associated with increased risk of atopic dermatitis (OR 1.88, P = 0.001) and allergic rhinoconjunctivitis (OR 1.34, P = 0.046), and hookworm with increased risk of allergic rhinoconjunctivitis (OR 2.77, P = 0.021). A positive stool examination for Ascaris lumbricoides infection was negatively associated with atopic dermatitis (OR 0.22, P = 0.007). Asthma and atopy were unrelated to helminth infections. Conclusion Current A. lumbricoides infection protects against atopic dermatitis in Cuban children, while past infection with E. vermicularis and hookworm are risk factors for allergic rhinoconjunctivitis and/or atopic dermatitis. Apparently, interactions differ depending on the type of helminth and atopic disease and on the time of helminth infestation.     

Effect of breast-feeding on the development of atopic dermatitis

Atopy can be defined as the genetically determined risk to develop allergic disease. Avoidance of one specific allergen may decrease the risk for sensitization against this allergen, but it will not affect atopy. Our aim was to investigate if exclusive breast-feeding is associated with atopic dermatitis during the first 5 years of life. Data on 200 children were taken from parental-administered questionnaires from a case control study in Birjand - Iran (recruited 2003) comprised of a case (100 children with atopic dermatitis) and a control (100 normal children) subgroup. Outcomes were physician-diagnosed atopic dermatitis (AD) and itchy rash. Data were analyzed by using SPSS package, Chi square and Exact Fisher tests.Thirty-four of the case and 50 of control group were exclusively breast-fed, whereas 6 of the case and 2 of control group were exclusively cow milk-fed. These differences were statistically significant. (P less than 0.05). Duration of breast-feeding in case and control group was different. These differences were statistically significant (P less than 0.001). Duration of cow's milk formula feeding in case and control group was different, but these differences were not statistically significant. (P=0.6) Positive family history of allergy in case and control group was 63% and 23% respectively and this difference was statistically significant (P less than 0.001). These findings support the hypothesis that exclusive breast-feeding is a protective factor for development of atopic dermatitis if compared with conventional cow's milk formula.     

Myelitis associated with atopic disorders in Japan: a retrospective clinical study of the past 20 years

OBJECTIVE: To clarify the clinical features of myelitis associated with atopic disorders in Japanese patients. SUBJECTS AND METHODS: We retrospectively studied the clinical, immunological and electrophysiological features of 68 consecutive patients with myelitis of acute or subacute onset diagnosed at Kyushu University Hospital during the past 20 years. RESULTS: While only 2 of 28 (7%) patients with myelitis diagnosed between 1979 and 1993 had either atopic dermatitis (AD) or bronchial asthma (BA), 19 of 40 (48%) patients with myelitis diagnosed between 1994 and 1998 did. Among the 40 patients with myelitis diagnosed between 1994 and 1998, 19 patients with either AD or BA as well as 21 patients without either disease showed a significantly higher level of serum total IgE, higher frequency of hyperIgEaemia and higher frequency of mite antigen-specific IgE than 82 healthy controls. Myelitis patients with AD presenting as persistent paresthesia/dysesthesia in all four limbs showed cervical cord lesions on MRI and abnormalities in upper limb motor evoked potentials but no abnormalities in the cerebrospinal fluid (CSF), while myelitis patients with BA showed preferential involvement of the lower motor neurons clinically and electromyographically. In addition, 12 patients with myelitis who had hyperIgEaemia and mite antigen-specific IgE but neither AD nor BA showed incomplete transverse myelitis with mild motor disability and few CSF abnormalities. CONCLUSION: The clinical features of myelitis associated with atopic disorders were in part distinguished by the type of preceding atopic disorder, and also were different from those of hyperIgEaemic myelitis with no preceding atopic disorders.