Embryonic-stem-cell-derived mesenchymal stem cells relieve experimental contact urticaria by regulating the functions of mast cells and T cells.

Contact urticaria (CU) is an inflammatory skin disorder triggered by specific substances upon skin contact, leading to immediate acute or chronic manifestations characterized by swelling and redness. While mesenchymal stem cells (MSCs) are increasingly recognized for their therapeutic potential in immune diseases, research on the efficacy and mechanisms of stem cell therapy for urticaria remains scarce. This study investigates the regulatory role of embryonic-stem-cell-derived multipotent MSCs (M-MSCs) administered in a CU mouse model. Therapeutic effects of M-MSC administration were assessed in a Trimellitic anhydride-induced contact urticaria model, revealing significant inhibition of urticarial reactions, including ear swelling, itchiness, and skin lesion. Moreover, M-MSC administration exerted control over effector T cell activities in major lymphoid and peripheral tissues, while also suppressing mast cell degranulation in peripheral tissues. Notably, the inhibitory effects mediated by M-MSCs were found to be TGF-ß-dependent. Our study demonstrates the capacity of M-MSCs to regulate contact urticaria in a murine model, harmonizing the activation of inflammatory T cells and mast cells. Additionally, we suggest that TGF-ß derived from M-MSCs could play a pivotal role as an inhibitory mechanism in contact urticaria.

Effects of the immunoglobulin/histamine complex on panic disorder concurrent with chronic spontaneous urticaria: a case report.

BACKGROUND: Panic disorder and panic attacks are two of the most common problems in psychiatry. A psychoimmunological correlation between allergic diseases and panic disorder has been strongly suggested. Histamine H1 receptor antagonists have been suggested as alternative drugs for the treatment of panic disorder. Chronic spontaneous urticaria (CSU) and panic disorder improved simultaneously with selective serotonin reuptake inhibitor antidepressants. Panic disorder has also been treated with the antihistamine chlorpheniramine. The immunoglobulin/histamine complex is a histamine-fixed immunoglobulin preparation that was reported to be effective in treating CSU. This case report describes the successful treatment of a patient with concomitant panic disorder and CSU for 23 years using immunoglobulin/histamine complex therapy. CASE PRESENTATION: This report describes a 52-year-old female Korean patient who suffered from CSU with panic disorder for 23 years. Basic allergy tests (blood tests and skin prick tests) were conducted before and after treatment for the evaluation of allergic conditions. A multiple allergosorbent test (MAST) for the detection of allergen-specific IgE levels was also performed. The clinical severity of CSU was evaluated using the urticaria severity score system. Diagnostic interviews systematically assessed the diagnostic criteria outlined by the DSM-V, and the patient was evaluated before, during and after treatment using the Beck Depression Inventory (BDI-2) for depression, the State-Trait Anxiety Inventory (STAI) for anxiety and the Beck Hopelessness Score (BHS) for hopelessness. The patient received 2 ml of Histobulin™ (12 mg human immunoglobulin/0.15 µg histamine complex) once a week by subcutaneous injection for the treatment of CSU. Initial improvement of CSU was achieved after the third injection. After the twenty-seventh injection of Histobulin™, she showed no symptoms or signs and ceased allergic medication use. With the remission of CSU, allergic rhinitis was also completely resolved. The frequency of the common cold was significantly decreased during and after treatment. The medication frequency and development of clinical manifestations of panic disorder changed in parallel with the clinical severity of CSU. Moreover, the patient exhibited no clinical manifestations and ceased medication for panic disorder and sleeping pills for insomnia simultaneously with the remission of CSU. In the psychological evaluation, the BDI, STAI and BHS scores improved accordingly. CONCLUSIONS: The immunoglobulin/histamine complex was effective in treating CSU and concomitant panic disorder in this patient and could be effective in treating some types of panic disorder. Considering the mechanisms of action of histamine and the immunoglobulin/histamine complex together with the patient's clinical progress, histamine seemed to be related to panic disorder in this case. The concept of histamine-mediated syndromes, including allergies and psychiatric disorders, shows that a wider disease identity may be needed. Further studies on the immunopathogenesis of panic disorder and the mechanisms of action of the immunoglobulin/histamine complex are necessary.

Treatment of primary eosinophilic colitis using immunoglobulin/histamine complex.

Primary eosinophilic colitis (PEC) is a primary eosinophilic gastrointestinal disorder, and immunoglobulin/histamine complex (IHC) may be an effective therapeutic for PEC. IHC has a nonallergen-specific antinociceptive effect in the treatment of histamine-mediated pain.

Immunotherapy using Histobulin™ in psoriasis: A case report.

There is no cure for psoriasis. A psoriasis patient was treated with Histobulin™. The patient's clinical symptoms and signs disappeared after the eighth injection and did not recur for more than 18 months. Histobulin™ was effective in the treatment of psoriasis and is suggested as a curative therapeutic for psoriasis.

Induction of remission in chronic urticaria by immunotherapy using immunoglobulin/histamine complex (Histobulin™): a case report.

BACKGROUND: Symptom control is a major concern in chronic urticaria. Histobulin™ is a histamine/immunoglobulin complex that has been approved for allergic rhinitis, bronchial asthma and chronic urticaria in some countries. Not only has the immunoglobulin/histamine complex been reported to be effective in allergic diseases, including chronic urticaria, but recently, the possibility of remission induction in chronic urticaria by the immunoglobulin/histamine complex has been reported. CASE PRESENTATION: Histobulin™ was administered until remission was induced instead of fixing the number of administrations in four cases of chronic urticaria. Two patients showed an early response and finished treatment with 12 injections of Histobulin™, and the other two patients showed a late response and were injected 43 and 46 times. Remission was induced successfully in all four cases. CONCLUSIONS: Histobulin™ is not only effective but also induces remission in CSU. The Histobulin™ therapy protocol in CSU may be better if the treatment is continued until remission is achieved. Based on the responses of the patients, early responders and late responders were present. The progression of the disease during treatment consisted of a slow improvement phase and a rapid improvement phase. Uniquely, the appropriate allergy laboratory results, including blood eosinophil fraction, total IgE and eosinophil cationic protein level, were normal in all 4 cases. Further studies concerning the mechanisms of Histobulin™ may be needed.

Mesenchymal stem/stromal cell therapy in atopic dermatitis and chronic urticaria: immunological and clinical viewpoints.

Allergic diseases are immune-mediated diseases. Allergies share a common immunopathogenesis, with specific differences according to the specific disease. Mesenchymal stem/stromal cells (MSCs) have been applied to people suffering from allergic and many other diseases. In this review, the immunologic roles of MSCs are systemically reviewed according to disease immunopathogenesis from a clinical viewpoint. MSCs seem to be a promising therapeutic modality not only as symptomatic treatments but also as causative and even preventive treatments for allergic diseases, including atopic dermatitis and chronic urticaria.

Histobulin as a complementary but essential therapeutic for Intravenous Immune Globulin Therapy of Pfeiffer-Weber-Christian disease with multiple allergic diseases and its effects on allergic disease: A case report.

Histobulin is complementary to IVIG therapy but is an essential therapeutic for PWCD. Histoublin is recommended not only in atopic dermatitis and multiple food allergies but also in patients with multiple allergic diseases.

Intravenous Immune Globulin (IVIG) Therapy After Unsuccessful Treatment with Corticosteroid and Cyclosporine A in Pfeifer-Weber-Christian Disease: A Case Report.

BACKGROUND Pfeifer-Weber-Christian disease (PWCD), also referred to as idiopathic nodular panniculitis, is a rare idiopathic disease characterized by lobular panniculitis of adipose tissue with systemic symptoms and multiple organ involvement and is usually treated with corticosteroids and cyclosporine A. We report a case of PWCD that was unresponsive to standard treatment but responded to intravenous immune globulin (IVIG) therapy. CASE REPORT A 35-year-old Korean woman presented with fever, malaise, myalgia, and painful nodules in the left breast. Histology of the breast nodules showed lobular panniculitis consistent with PWCD. She did not respond to corticosteroid and cyclosporine A. She was effectively treated with intravenous immune globulin (IVIG). IVIG therapy began with 60 g (1 g/kg) 4 times per week, 2 times every other week. Subsequently, the IVIG dose was reduced for maintenance therapy to 25 g (400 mg/kg) twice every other week and monthly. The patient showed immediate and dramatic improvement. General signs and symptoms, such as fever, malaise, and myalgia, were absent, and the masses had nearly subsided, with several very small hard nodules remaining for 3 months until the time of this report. CONCLUSIONS IVIG was an effective immunomodulatory therapeutic for PWCD in this case. This report shows that PWCD is a rare condition that is difficult to diagnose, but the histopathology of nodular panniculitis supports the diagnosis. In cases that do not respond to standard immunosuppressive therapy, including corticosteroids and cyclosporine A, IVIG therapy may lead to a favorable response with rapid symptomatic relief.

Immunotherapy using Histobulin in atopic dermatitis.

Histobulin was effective in atopic dermatitis. Allergic diseases may be classified as allergen-specific and non-allergen-specific. Histobulin appears to exert immediate preventive effects against upper respiratory infection.

CD1dhiPD-L1hiCD27+ Regulatory Natural Killer Subset Suppresses Atopic Dermatitis.

Effector and regulatory functions of various leukocytes in allergic diseases have been well reported. Although the role of conventional natural killer (NK) cells has been established, information on its regulatory phenotype and function are very limited. Therefore, the objective of this study was to investigate the phenotype and inhibitory functions of transforming growth factor (TGF)-ß-producing regulatory NK (NKreg) subset in mice with MC903-induced atopic dermatitis (AD). Interestingly, the population of TGF-ß-producing NK cells in peripheral blood monocytes (PBMCs) was decreased in AD patients than in healthy subjects. The number of TGF-ß+ NK subsets was decreased in the spleen or cervical lymph node (cLN), but increased in ear tissues of mice with AD induced by MC903 than those of normal mice. We further observed that TGF-ß+ NK subsets were largely included in CD1dhiPD-L1hiCD27+ NK cell subset. We also found that numbers of ILC2s and TH2 cells were significantly decreased by adoptive transfer of CD1dhiPD-L1hiCD27+ NK subsets. Notably, the ratio of splenic Treg per TH2 was increased by the adoptive transfer of CD1dhiPD-L1hiCD27+ NK cells in mice. Taken together, our findings demonstrate that the TGF-ß-producing CD1dhiPD-L1hiCD27+ NK subset has a previously unrecognized role in suppressing TH2 immunity and ILC2 activation in AD mice, suggesting that the function of TGF-ß-producing NK subset is closely associated with the severity of AD in humans.

Tango therapy for Parkinson's disease: Effects of rush elemental tango therapy.

Tango therapy is very effective by applying tango elements according to the clinical severity and status of a patient. Maximization of the clinical effects of tango therapy in patients with Parkinson's disease may be achieved by the proper prescription of tango elements according to the clinical status of a patient.

Immunotherapy of lidocaine allergy by intravenous desensitization using IFN-gamma from a case: Overcoming impediments using IFN-gamma during desensitization.

Anaphylactic reaction to lidocaine has been reported during a dental procedure. In this trial, a patient who required local anesthesia for dental treatment was desensitized successfully to intravenous lidocaine using IFN-gamma. Practical general protocols and principles are suggested for the general application of this method for other intravenous drugs.

Reliability and Validity of the Korean-Parental Self-Efficacy with Eczema Care Index.

BACKGROUND: Atopic dermatitis is a global problem affecting children, and its prevalence in Korea is steadily increasing. Since it is a chronically relapsing inflammatory skin disease, caregiver management of young children's atopic dermatitis is crucial for positive treatment outcomes. A factor that contributes to adherence to recommended prescriptions is parents' self-efficacy. However, accurate measurements of parental self-efficacy in relation to disease-specific task management are scarce. OBJECTIVES: This study examined the psychometric properties of the Korean language version of the Parental Self-Efficacy with Eczema Care Index (K-PASECI). METHODS: One hundred twenty five mothers of children younger than 13 years old who had atopic dermatitis were recruited from three tertiary hospitals across Korea. The K-PASECI was developed in accordance with the published guidelines. Psychometric testing included factor analysis, internal consistency testing, and concurrent validity analysis by comparing K-PASECI domains with parenting self-efficacy subscales. RESULTS: Factor analysis revealed a four-factor structure that explained 69.4% of the variance. The four factors were as follows; managing a child's symptoms and behaviour, communicating with medical staff, managing medication, and using moisturizer as part of routine management. The findings showed acceptable internal consistency (α=.94) and a moderate positive correlation with parenting self-efficacy (r=.48, p<.001). CONCLUSION: The K-PASECI, a reliable and valid scale for measuring self-efficacy in parents caring for children with atopic dermatitis, may be used in clinical and research settings to measure parents' self-efficacy in Korea, as well as in other English-speaking countries.

The effects of elimination diet on nutritional status in subjects with atopic dermatitis.

A food allergy is an adverse health effect arising from a specific immune response that occurs reproducibly upon exposure to a given food. In those with food allergies that are thought to cause aggravation of eczema, food avoidance is important. The objective of this study was to research the nutritional status of patients with food allergies. A total of 225 subjects diagnosed with atopic dermatitis underwent a skin prick test as well as measurement of serum immunoglobulin E. Food challenge tests were conducted using seven food items: milk, eggs, wheat, soybeans, beef, pork, and chicken. At post-food challenge visits to the test clinic, participants completed a three-day dietary record, which included two week days and one weekend day, in order to evaluate energy intake and diet quality during the challenge. We analyzed nutrient intake based on differential food allergens. Subjects with a food allergy to milk showed lower intake of Ca, Zn, and vitamin B2, and subjects with a food allergy to egg showed lower intake of vitamin A, B1, B2, niacin, and cholesterol. Subjects with a food allergy to wheat and soybean showed lower intake of Ca, P, Fe, K, Zn, vitamin B2, vitamin B6, and niacin; and subjects with a food allergy to beef, pork, and chicken showed lower intake of Fe and higher intake of K, vitamin A, B2. Subjects with atopic dermatitis were lacking in several nutrients, including vitamin A and vitamin C. A greater number of food allergies showed an association with a greater number of nutrient intake deficiencies. Allergen avoidance is the basic treatment for atopic dermatitis. However, when the allergen is food, excessive restriction can lead to nutrition deficiency. Findings of this study suggest the necessity for enhanced nutritional education in order to provide substitute foods for patients with food allergies who practice food restriction.

Specific Oral Tolerance Induction Using IFN-Gamma in 2 Cases of Food-Dependent Exercise-Induced Anaphylaxis.

Anaphylaxis induced by exercise after the intake of certain foods is referred to as food-dependent exercise-induced anaphylaxis (FDEIA). Only the preventive medication such as oral sodium cromoglycate and oral combined cetirizine-montelukast was tried in FDEIA. Specific oral tolerance induction (SOTI) using IFN-gamma was tried in 2 cases of FDEIA for wheat. Merely, exercise accompanied every treatment just after the intake of allergenic foods during treatment. Patients acquired tolerance for wheat in both cases successfully. After treatment, two patients take wheat in their food living freely. Conclusively, SOTI using IFN-gamma was effective as the causative treatment for allergenic foods in FDEIA.

Polydesensitisation with reducing elevated serum total IgE by IFN-gamma therapy in atopic dermatitis: IFN-gamma and polydesensitisation (PDS).

BACKGROUND: AD patients exhibit sensitisation to multiple allergens due to a Th1/Th2 imbalance. Until now, it was impossible to improve the polysensitised status and elevated serum total IgE levels. In this study, the effects of IFN-gamma on systemic polysensitisation to multiple allergens and on serum total IgE levels are investigated. METHODS: A total of 44 AD patients whose food allergies were completely controlled and who were polysensitised to multiple allergens according to the SPT were selected. Twenty-two of these patients received IFN-gamma therapy twice a week for 2 months, and 22 patients did not receive this therapy. The blood eosinophil % and serum total IgE levels were assessed, and a skin prick test for 51 allergens was performed before and after the IFN-gamma therapy. RESULTS: With IFN-gamma therapy, the polysensitisation status was improved, as demonstrated by a decrease in the positive allergen count and skin reactivity (systemic polydesensitisation). The improvement in the polysensitised status was accompanied by a decrease in serum total IgE levels. The change in serum total IgE levels was significantly correlated with the change in polysensitisation status. CONCLUSIONS: IFN-gamma therapy resulted in systemic polydesensitisation with reduced levels of serum total IgE. IFN-gamma is indicated in AD patients with high serum total IgE levels whose food allergies are well controlled and who are polysensitised to multiple allergens.

Clinical significance and evaluation of polysensitisation using skin sensitisation profiling in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic allergic inflammatory disease characterised by late eczematous lesions and allergenic sensitisation that occur. Skin prick testing has been used for the causative investigation of individual allergens. However, there exists no proper tool to evaluate polysensitisation status. In this study, skin sensitisation indices were suggested, and the clinical significance of polysensitisation was evaluated. METHODS: A total of 188 AD patients were involved in this study. Blood tests including blood eosinophil % and serum total IgE were conducted. Skin prick tests for 50 important allergens were performed. The skin sensitisation index (SSI) was compared with the blood eosinophil % and the serum total IgE. RESULTS: The degree of sensitisation may be related to the serum total IgE rather than the number of allergens to which a patient is sensitised. The skin sensitisation profile was associated with IgE-related laboratory results but not with clinical activity or blood eosinophil %. CONCLUSIONS: For the evaluation of polysensitisation, skin sensitisation profiles may be needed and the skin sensitisation profile was useful for the description of polysensitisation. Polysensitisation seems to be one mechanism for the elevation of serum total IgE. Further studies may be needed to ascertain the clinical significance of skin polysensitisation and the application of the skin sensitisation profile in clinical use.

Characterization of food allergies in patients with atopic dermatitis.

We examined the characteristics of food allergy prevalence and suggested the basis of dietary guidelines for patients with food allergies and atopic dermatitis. A total of 2,417 patients were enrolled in this study. Each subject underwent a skin prick test as well as serum immunoglobulin E (IgE) measurement. A double-blind, placebo-controlled food challenge was conducted using milk, eggs, wheat, and soybeans, and an oral food challenge was performed using beef, pork, and chicken. Food allergy prevalence was found among 50.7% in patients with atopic dermatitis. Among patients with food allergies (n = 1,225), the prevalence of non-IgE-mediated food allergies, IgE-mediated food allergies, and mixed allergies was discovered in 94.9%, 2.2%, and 2.9% of the patients, respectively. Food allergy prevalence, according to food item, was as follows: eggs = 21.6%, milk = 20.9%, wheat = 11.8%, soybeans = 11.7%, chicken = 11.7%, pork = 8.9% and beef = 9.2%. The total number of reactions to different food items in each patient was also variable at 45.1%, 30.6%, 15.3%, 5.8%, 2.2%, and 1.0% for 1 to 6 reactions, respectively. The most commonly seen combination in patients with two food allergies was eggs and milk. The clinical severity of the reactions observed in the challenge test, in the order of most to least severe, were wheat, beef, soybeans, milk, pork, eggs, and chicken. The minimum and maximum onset times of food allergy reactions were 0.2-24 hrs for wheat, 0.5-48 hrs for beef, 1.0-24 hrs for soybeans, 0.7-24 hrs for milk, 3.0-24 hrs for pork, 0.01-72 hrs for eggs, and 3.0-72 hrs for chicken. In our study, we examined the characteristics of seven popular foods. It will be necessary, however, to study a broader range of foods for the establishment of a dietary guideline. Our results suggest that it may be helpful to identify food allergies in order to improve symptoms in patients with atopic dermatitis.

In Vitro Induction of Allergen-Specific Interleukin-10-Producing Regulatory B Cell Responses by Interferon-γ in Non-Immunoglobulin E-Mediated Milk Allergy.

PURPOSE: Specific oral immunotherapy (SOIT) using interferon-γ (IFN-γ) has been successful as a food allergy treatment. Interleukin-10 (IL-10)-producing regulatory B cells (Br1s) play a role in immune tolerance to food allergens. In addition, IFN-γ shows tolerogenic effects on allergen-induced Br1 responses. METHODS: Eleven patients that were allergic to cow's milk and 12 milk-tolerant subjects were selected by double-blind placebo-controlled food challenge (DBPCFC) and clinical characteristics. The immunomodulatory effects of IFN-γ on allergen-specific Br1 responses were evaluated in 6 milk allergy patients and 8 milk-tolerant subjects. Peripheral blood mononuclear cells (PBMCs) from subjects were stimulated with casein and/or IFN-γ and analyzed by flow cytometry. RESULTS: IFN-γ had no effect on total cell counts or the proportion of Br1 cells in PBMCs. IFN-γ stimulation did not change total Br1 cell counts or the percentage of Br1s among CD5(+) B cells in the milk allergy or the milk-tolerant groups. In the milk allergy group, Br1 counts were not different between the control and the casein stimulation but significantly increased in the IFN-γ + casein stimulated cells, and the Br1 fractions were decreased after casein stimulation and recovered in the addition of IFN-γ for stimulation. In the milk-tolerant group, Br1 counts increased in the casein stimulated cells and in the IFN-γ + casein stimulated cells, but the increase was significantly less when IFN-γ was added, and the Br1 fractions were increased after casein stimulation and IFN-γ + casein stimulation, that was not significant when IFN-γ was added. CONCLUSIONS: IFN-γ-induced allergen-specific Br1 responses in the PBMCs of milk allergy patients play a role in milk allergen-specific tolerance induction in vitro. Further investigations into the molecular immunological mechanisms underlying the induction of allergen-specific Br1 responses are needed.