Impact of soymilk consumption on 2,4-dinitrofluorobenzene-induced contact hypersensitivity and gut microbiota in mice.

Soymilk is rich in phytochemicals such as soy isoflavones (SIs) and soyasaponins (SSs). Dietary SIs and SSs display inhibitory effects on contact hypersensitivity (CHS), which was reported in a mouse model for allergic contact dermatitis (ACD); however, the beneficial effects of soymilk consumption on CHS remain unknown. Here, we studied the effects of drinking soymilk on CHS and gut microbiota. Soymilk consumption attenuated ear oedema and swelling, decreased the infiltration of Gr-1-positive cells into ear tissues, and reduced the production of chemokine (C-X-C motif) ligand 2 and triggering receptor expressed on myeloid cells-1 in ear tissues. The analysis of bacterial 16S ribosomal RNA gene sequences indicated that CHS caused changes in the gut microbiota structure and that consuming soymilk reduced these changes. These results suggest that soymilk consumption may be of therapeutic value for patients with ACD and may help control the balance of intestinal microbiota.

Correlation of aspergillus skin hypersensitivity with the duration and severity of asthma.

Asthma is a significant health problem worldwide and Allergic Bronchopulmonary aspergillosis (ABPA) complicates the course of 1-2% of patients of asthma. Aspergillus skin hypersensitivity (AH) is the first step for diagnosis of ABPA. This study was conducted to know the correlation of AH with severity and duration of asthma. Patients, age >15 years, of asthma attending this hospital from January 2015 to December 2015 were included. Asthma was diagnosed clinically and confirmed with spirometry. Of 282 patients 206 patients were AH positive. The AST-positivity in patients having severe asthma (96.8%) was higher than that in patients having mild (36.8%) and moderate asthma (80.4%). The median (IQR) duration of asthma of AH positive patients was 5.0 yrs. This study emphasized the need of ABPA screening by intradermal skin test especially in patients having severe asthma and/or those having asthma for longer duration in order for early diagnosis of ABPA.

Expression of activation-induced cytidine deaminase enhances the clearance of pneumococcal pneumonia: evidence of a subpopulation of protective anti-pneumococcal B1a cells.

We describe a protective early acquired immune response to pneumococcal pneumonia that is mediated by a subset of B1a cells. Mice deficient in B1 cells (xid), or activation-induced cytidine deaminase (AID(-/-) ), or invariant natural killer T (iNKT) cells (Jα18(-/-) ), or interleukin-13 (IL-13(-/-) ) had impaired early clearance of pneumococci in the lung, compared with wild-type mice. In contrast, AID(-/-) mice adoptively transferred with AID(+/+) B1a cells, significantly cleared bacteria from the lungs as early as 3 days post infection. We show that this early bacterial clearance corresponds to an allergic contact sensitivity-like cutaneous response, probably due to a subpopulation of initiating B1a cells. In the pneumonia model, these B1a cells were found to secrete higher affinity antigen-specific IgM. In addition, as in contact sensitivity, iNKT cells were required for the anti-pneumococcal B1a cell initiating response, probably through early production of IL-13, given that IL-13(-/-) mice also failed to clear infection. Our study is the first to demonstrate the importance of AID in generating an appropriate B1a cell response to pathogenic bacteria. Given the antibody affinity and pneumonia resistance data, natural IgM produced by conventional B1a cells are not responsible for pneumonia clearance compared with the AID-dependent subset.

Countering Staphylococcus Overgrowth During Patch Testing in Children with Moderate to Severe Atopic Dermatitis.

BACKGROUND: Patients with moderate to severe atopic dermatitis (AD) often have a concurrent diagnosis of contact dermatitis, but patch testing in these patients presents a unique set of challenges. Barrier impairment and Staphylococcus aureus colonization and infection, along with the sealed occlusion that takes place during the patch testing procedure, can create an optimal environment for bacterial overgrowth. AIMS: To identify patients at risk for S. aureus overgrowth during patch testing and provide pre- and peripatch testing interventions to aid clinicians in obtaining the best possible patch test results in this complicated population. MATERIALS AND METHODS: A retrospective review was performed of five patients with moderate to severe AD for which S. aureus overgrowth and superinfection complicated patch test evaluation. RESULTS: All five patients were able to complete the patch test procedure and all had relevant positive patch test reactions. Complications during patch testing included erythema, oozing, foul odor under the patches, and purulent material at the patch sites. One patient had a culture performed during patch testing that showed methicillin-sensitive S. aureus. DISCUSSION: Patch testing can play an important role in the examination and management of patients with refractory AD. CONCLUSIONS: Moderate to severe AD and concern regarding S. aureus overgrowth should not preclude patch testing.

Nonpathogenic bacteria alleviating atopic dermatitis inflammation induce IL-10-producing dendritic cells and regulatory Tr1 cells.

The beneficial effects of nonpathogenic bacteria are increasingly being recognized. We reported in a placebo-controlled study with atopic dermatitis (AD) patients that cutaneous exposure to lysates of nonpathogenic bacteria alleviates skin inflammation. To now unravel underlying mechanisms, immune consequences of sensing nonpathogenic bacterium Vitreoscilla filiformis lysate (Vf) were characterized analyzing (1) differentiation of dendritic cells (DCs) and, consecutively, (2) effector functions of DCs and T helper (Th) cells in vitro and in a murine model of AD in NC/Nga mice in vivo. Topical treatment with Vf significantly reduced AD-like inflammation in NC/Nga mice. Importantly, cutaneous exposure to Vf in combination with the allergen FITC significantly also reduced subsequent allergen-induced dermatitis indicating active immune modulation. Indeed, innate sensing of Vf predominantly induced IL-10-producing DCs, which was dependent on Toll-like receptor 2 (TLR2) activation. Vf-induced IL-10+ DCs primed naive CD4+ T helper cells to become regulatory IFN-γ(low) IL-10(high) Tr1 (type 1 regulatory T) cells. These IL-10(high) Tr1 cells were also induced by Vf in vivo and strongly suppressed T effector cells and inflammation. In conclusion, we show that innate sensing of nonpathogenic bacteria by TLR2 induces tolerogenic DCs and regulatory Tr1 cells suppressing T effector cells and cutaneous inflammation. These findings indicate a promising therapeutic strategy for inflammatory skin diseases like AD.

Reduced inflammatory threshold indicates skin barrier defect in transglutaminase 3 knockout mice.

Recently, a transglutaminase 3 knockout (TGM3/KO) mouse was generated that showed impaired hair development, but no gross defects in the epidermal barrier, although increased fragility of isolated corneocytes was demonstrated. Here we investigated the functionality of skin barrier in vivo by percutaneous sensitization to FITC in TGM3/KO (n=64) and C57BL/6 wild-type (WT) mice (n=36). Cutaneous inflammation was evaluated by mouse ear swelling test (MEST), histology, serum IgE levels, and by flow cytometry from draining lymph nodes. Inflammation-induced significant MEST difference (P<0.0001) was detected between KO and WT mice and was supported also by histopathology. A significant increase of CD4+ CD25+-activated T cells (P<0.01) and elevated serum IgE levels (P<0.05) in KO mice indicated more the development of FITC sensitization than an irritative reaction. Propionibacter acnes-induced intracutaneous inflammation showed no difference (P=0.2254) between the reactivity of WT and KO immune system. As in vivo tracer, FITC penetration from skin surface followed by two-photon microscopy demonstrated a more invasive percutaneous penetration in KO mice. The clinically uninvolved skin in TGM3/KO mice showed impaired barrier function and higher susceptibility to FITC sensitization indicating that TGM3 has a significant contribution to the functionally intact cutaneous barrier.

Caring for new mothers: diagnosis, management and treatment of nipple dermatitis in breastfeeding mothers.

Breastfeeding is thought to be the most optimal form of infant nutrition. Nursing mothers are generally advised to continue breastfeeding until the infant is two years of age or beyond. Unfortunately, however, a majority of nursing mothers will discontinue breastfeeding much earlier than recommended. The most common reason for early discontinuation of breastfeeding is nipple pain. It is, therefore, essential that dermatologists know how to appropriately diagnose and effectively treat nipple pain associated with nipple dermatitis among nursing mothers. This review article provides a detailed discussion on the clinical features and management of various causes of nipple dermatitis during lactation, including problems with infant latch-on, congenital oral anomalies, plugged lactiferous ducts, atopic dermatitis, irritant contact dermatitis, allergic contact dermatitis, yeast infections, bacterial infections, herpes simplex virus, and Raynaud's phenomenon of the nipple.

Tropical dermatology: marine and aquatic dermatology.

UNLABELLED: Dermatoses caused by marine organisms are frequently seen in dermatology clinics worldwide. Cutaneous injuries after exposure to marine environments include bacterial and fungal infections and lesions caused by aquatic plants and protists. Some of these diseases are well known by dermatologists, such as Vibrio vulnificus septicemia and erysipeloid, but others are uncommon, such as envenomation caused by ingestion or contact with certain dinoflagellates or cyanobacteria, which are associated with rashes that can begin within minutes after exposure. Many marine/aquatic invertebrates, such as sponges, cnidarians, echinoderms, crustaceans, and mollusks, are associated with different kinds of dermatologic lesions that can vary from irritant or allergic contact dermatitis to physical trauma and envenomations. These cutaneous lesions may result in mild local reactions or can be associated with severe systemic reactions. Invertebrate animals, such as cnidarians, sea urchins, and worms, and aquatic vertebrates, such as venomous fishes and stingrays, are commonly associated with skin lesions in many countries, where they can constitute occupational dermatoses among fishermen and scuba divers, but they can also be observed among persons who contact these animals in kitchens or beaches. The presence of unusual lesions, a recent travel history, and/or a report of contact with an aquatic environment (including ownership of a marine or freshwater aquarium) should alert the dermatologist to the etiology of the cutaneous problems. LEARNING OBJECTIVES: After completing this learning activity, participants should be able to recognize the cutaneous manifestations of marine/aquatic infections, bites, stings, and wounds, etc., treat the cutaneous manifestations of marine/aquatic injuries, and help prevent marine/aquatic injuries.

Staphylococcal enterotoxin B enhances a flare-up reaction of murine contact hypersensitivity through up-regulation of interferon-gamma.

BACKGROUND: We often see aggravation of eczematous skin lesions associated with bacterial infection, but the mechanism of this phenomenon is unclear. Staphylococcus aureus is known to colonize on the eczematous lesion and produce some exotoxins, which act as bacterial superantigens. OBJECTIVES: To investigate the potential role of superantigens in chronic dermatitis, we investigated the effect of staphylococcal enterotoxin B (SEB) on the skin reaction, the proliferative response and the cytokine production of local lymph node cells in the mouse model of contact hypersensitivity reaction. METHODS: Sensitized BALB/c mice were repeatedly challenged with dinitrofluorobenzene (DNFB), and intravenously injected with SEB and dinitrobenzne sulfonic acid sodium salt (DNBS). The ear swelling response was measured after DNBS injection. Cervical lymph node cells of those mice were cultured with DNBS in vitro. Their proliferative responses and the production of cytokines were assessed. RESULTS: SEB markedly enhanced the flare-up reaction of ear swelling induced by DNBS, the proliferative response of lymph node cells and the production of IFN-gamma. In contrast, the production of IL-5 was decreased. CONCLUSIONS: The present study may provide some clues for elucidating the mechanism involved in the exacerbation of dermatitis associated with staphylococcal infection.

[The pathophysiology and defense mechanism against superficial and subcutaneous fungal infection].

To determine the pathophysiology of the fungal infection and defense mechanisms against superficial dermatomycosis, two series of experimental infections of Trychophyton mentagrophytes were made on the forearm of a male volunteer. One series was applied topical steroid ointment, the other the vehicle alone. The infected sites were biopsied from each row weekly up to the 4th week, and the set of sites were studied and compared clinically, histopathologically and immunohistochemically. For the study against subcutaneous fungal infection, the same experiments were studied using the subcutaneous inoculation of Sporothrix schenckii. The pathophysiology of the superficial dermatophytosis was thought to be the same as those of the contact (allergic) dermatitis, including the physiodynamics of CD-1 cells. The principal mechanism of the defense lay in the removal of the foreign materials (fungi) together with keratinocytes whose turnover increased because of the eczematous reaction. It was proved that the topical application of steroid ointment suppressed the immune reactions locally, thus forming a paradoxical feature with little inflammatory reaction and abundant fungal elements (so-called atypical tinea). The pathophysiology of the subcutaneous fungal infection was thought to be a suppurative granulomatous reaction and pathologically showed a mixed cell granuloma. The neutrophils and macrophages engulfed and digested the fungi in the forefront, but the circumference was surrounded by epithelioid cells and/or foreign body granuloma. Transepithelial elimination also played some role in the defense. It was proved that when the defense mechanism was weakened by the topically applied steroid ointment, not only the clinical symptoms but also the fungicidal tissue reaction were subdued, and histocytes only engulfed fungi to protect them from dispersion. The trichophytin reaction turned positive on the 14th day, and the sporotrichin reaction on the 7th day.

Repeated topical challenge with chemical antigen elicits sustained dermatitis in NC/Nga mice in specific-pathogen-free condition.

NC/Nga mice are known to develop skin lesions resembling to atopic dermatitis (AD) in conventional but not in specific-pathogen-free (SPF) condition. An epicutaneous application of 2,4-dinitrofluorobenzene (DNFB) increased skin thickness in C3H as well as NC/Nga mice in SPF environment, and the response was enlarged by repeating the challenge at weekly intervals. Although the skin reaction in C3H mice was ameliorated when the challenge was discontinued after the fifth application, the reaction in NC/Nga mice was sustained at least for 3 wk. Analyses of cytokine production by CD4+ cells from the draining lymph node proximal to the lesions revealed that, unlike C3H mice, NC/Nga mice fail to induce T helper 2 (Th2) cytokine interleukin-4 (IL-4), whereas the level of Th1 cytokine interferon-gamma in NC/Nga mice is equivalent to that of C3H mice. In addition, NC/Nga mice highly expressed IL-12, a cytokine-preventing formation of Th2 response, whereas C3H mice did not. Administration of anti-IL-12 antibody reduced duration of dermatitis in DNFB-treated NC/Nga mice. Taken together, our data suggest that IL-12 plays a role in the persistent skin reaction in NC/Nga mice. The action of IL-12 might be mediated by the decrease in IL-4 production.

[Pustular dermatitis in veterinarians following delivery in farm animals; an occupational disease]. / Pustulaire dermatitis bij dierenartsen na verlossingen van landbouwhuisdieren; een beroepsziekte.

OBJECTIVE: To assess the prevalence of contact dermatitis after deliveries in cattle or sheep among veterinarians. DESIGN: Retrospective. SETTING: Provinces of Groningen, Friesland, and Drenthe, The Netherlands. METHODS: By means of a short inquiry 310 veterinarians were asked whether and how often they had experienced pustular dermatitis after deliveries in cattle and sheep and what course the dermatitis had run. They were also asked about details of the deliveries (type of animal, condition of the foetus, course of the partus), about microbiological investigation, preventive measurements and therapy. RESULTS: The response to the questionnaires was 24.5%. One or more episodes of pustular dermatitis on an arm after a delivery in cattle or sheep was noticed by 62 (81.5%) of the 76 respondents. Sometimes it was associated with secondary symptoms like headache, fever and lymphadenitis. Listeria monocytogenes (7 times out of 13) and Salmonella dublin (4/13) were the agents cultured most often. CONCLUSION: Contact dermatitis after deliveries in cattle or sheep occurs frequently as an occupational disease of veterinarians.

Epidemic cutaneous sporotrichosis: report of 16 cases in Queensland due to mouldy hay.

We report an epidemic of sporotrichosis in a south-east Queensland rural community. Sporotrichosis is a fungal infection due to the organism Sporothrix schenckii, typically presenting with cutaneous lesions. Sixteen cases of cutaneous sporotrichosis were seen over a 9 month period in the Darling Downs region of Queensland. All patients had had contact with a batch of mouldy hay presumed to be contaminated by Sporothrix schenckii. Nine of 16 patients were male; the youngest patient was aged 11 and the oldest was 67 years of age. Lymphocutaneous sporotrichosis was seen in 50% of patients; the rest demonstrated the fixed cutaneous form. No cases of disseminated cutaneous or systemic sporotrichosis were seen. One case demonstrated lymphangitis related to sporotrichosis. No apparent difference in the duration to diagnosis was demonstrated to exist between lymphocutaneous or fixed cutaneous types.

Nonspecific modification of cellular immunity by Yersinia enterocolitica.

An isogenic pair of virulent and avirulent Yersinia enterocolitica O9 strains was used to examine the influence of the virulence plasmid on the non-specific modification of the cellular immunity in BALB/c mice after experimental infection with yersiniae. The modification of contact hypersensitivity response to dinitrofluorobenzene, resistance to the syngeneic lymphoma LSTRA, and resistance to Listeria monocytogenes was heavily influenced by the presence of the virulence plasmid. As a general rule for the modification of cellular immunity by yersiniae, the plasmid-bearing strain induced a short-term suppression followed by a potentiation, whereas the isogenic plasmid-less derivative induced only a short-term potentiation. The Yersinia-mediated enhancement of cellular immunity resulted in protection against infection with Listeria and partial protection against LSTRA transplantation. Results of Concanavalin A-induced proliferation of splenocytes from Yersinia-infected mice suggested a role for cytokines as gamma-interferon in the Yersinia-mediated immunopotentiation.

Vibrio in stinging seaweed: potential infection.

Toxic strains of the finely filamentous, velvety, dark-olive green to black algal organism, Microcolus Lyngbyaceus, (formerly Lyngbya majuscula Gomont, or "lyngbya") have been recognized as etiologic agent of "stinging seaweed" dermatitis (one of several forms of "swimmer's itch") in Hawaii since the late 1950s as reviewed. Lymphadenopathy, pustular folliculitus, and local infections have been reported in some persons.

Chronic cutaneous bacterial hypersensitivity dermopathy: a second case and six year evaluation of the first case.

A case we described and reported 6 years ago as chronic cutaneous granulomatous dermopathy was believed due to bacterial hypersensitivity. We now report a second case with similar features of chronic recurrent indolent inflammatory skin lesions, nondiagnostic skin biopsies, and failure to respond to antibiotics. In the absence of another diagnosis and because of the remarkably similar appearance to the first case, we initiated a therapeutic trial with corticosteroids, which induced a remission. The initial case has now been observed for 6 years, and the patient remains in remission on 5 mg of prednisone on alternate days. The second case was considered consistent with bacterial allergy because of IgG and IgE antibodies against common cutaneous bacteria. As there were no granulomas in the current patient's skin lesions, a new designation, chronic cutaneous bacterial hypersensitivity, has been assigned. The differential diagnosis and criteria for this clinical entity are discussed. Either a remission from prednisone or control with low-dose prednisone may be achieved in this dermopathy, which is both disfiguring and frightening to patients.