Successful Treatment of Autoimmune Urticaria with Low-Dose Prednisolone Therapy Administered for a Few Months: A Case Series of 42 Patients.

BACKGROUND: Chronic spontaneous urticaria (CSU) is defined as symptoms of urticaria persisting for 6 weeks or more without obvious cause. Autologous serum skin test (ASST) positivity in patients with CSU is considered to be associated with autoimmune urticaria (AIU). METHODS: In this retrospective study we retrieved the medical records of 1,073 urticaria patients seen at the Department of Dermatology and Allergology of Szeged University between January 2005 and February 2014. Forty-two patients (36 female and 6 male) met the study criteria by having CSU and giving positive results in the ASST. Our aim was to assess the clinical efficacy and safety of low-dose oral prednisolone therapy administered to patients with antihistamine-refractory ASST-positive CSU for a few months. Patients were given an initial dose (40 mg/day) of prednisolone until the complete resolution of the symptoms, usually 7-10 days, and then the dose was gradually decreased, as in other autoimmune diseases. RESULTS: Prednisolone therapy lasted for an average of 3.6 months and a complete long-lasting response was achieved in 35 of 42 AIU patients (83.3%). The follow-up period was at least 36 months (3 years) for each AIU patient; the longest follow-up time was 139 months (11.5 years). None of the patients reported any considerable side effects. CONCLUSION: Based on our results, we suggest that the use of this treatment could be an alternative for the treatment of AIU. Our present results also highlight the need for other therapies in a small percentage of AIU patients. Our results suggest that AIU represents a transient autoimmunity that can be successfully treated with low-dose steroid therapy administered for a few months.

Amoxicillin rash in patients with infectious mononucleosis: evidence of true drug sensitization.

BACKGROUND: It hasn't been clearly understood yet whether sensitization to antibiotics, the virus itself or transient loss of drug tolerance due to the virus, is responsible for the development of maculopapular exanthems following amoxicillin intake in patients with infectious mononucleosis. We aimed to examine whether sensitization to penicillin developed among patients with skin rash following amoxicillin treatment within infectious mononucleosis. METHODS: Ten patients were investigated for drug sensitization by lymphocyte transformation test and six patients were further tested by prick-, intradermal and patch tests employing the penicillin's main antigens. RESULTS: Lymphocyte transformation test showed negative results with amoxicillin, while one patient had positive reaction to cefixime. Six patients with suspected sensitization to amoxicillin were then investigated by in vivo tests. Prick tests were negative in all six patients, but the intradermal tests showed positive reactions in four patients. CONCLUSIONS: Our data demonstrate that in vitro testing is not sensitive enough in determining drug sensitization to penicillin. In vivo tests should be performed to detect sensitization and indeed with skin tests our results confirmed that sensitization to aminopenicillin may develop within infectious mononucleosis.

DermAll nanomedicine for allergen-specific immunotherapy.

Allergen-specific immunotherapy (ASIT) the only disease-modifying treatment for IgE-mediated allergies is characterized with long treatment duration and high risk of side effects. We investigated the safety, immunogenicity and efficacy of a novel ASIT, called DermAll, in an experimental allergic rhinitis model. We designed and characterized DermAll-OVA, a synthetic plasmid pDNA/PEIm nanomedicine expressing ovalbumin (OVA) as model allergen. DermAll-OVA was administered topically with DermaPrep device to target Langerhans cells. To detect the clinical efficacy of DermAll ASIT we quantified the nasal symptoms and characterized the immunomodulatory activity of DermAll ASIT by measuring cytokine secretion after OVA-stimulation of splenocytes and antibodies from the sera. In allergic mice DermAll ASIT was as safe as Placebo, balanced the allergen-induced pathogenic TH2-polarized immune responses, and decreased the clinical symptoms by 52% [32%, 70%] compared to Placebo. These studies suggest that DermAll ASIT is safe and should significantly improve the immunopathology and symptoms of allergic diseases. FROM THE CLINICAL EDITOR: A novel allergen-specific immunotherapy for IgE-mediated allergies is presented in this paper, using an experimental allergic rhinitis model and a synthetic plasmid pDNA/PEIm nanomedicine expressing ovalbumin as model allergen. Over 50% reduction of symptoms was found as the immune system's balance was favorably altered toward more TH2-polarized immune responses.

The rs3761548 polymorphism of FOXP3 is a protective genetic factor against allergic rhinitis in the Hungarian female population.

We aimed to study whether forkhead box P3 (FOXP3) polymorphisms contribute to allergic rhinitis (AR) in a Central-European population, the Hungarians, similarly as it was found in Han Chinese. A case-control study was performed and the genotype distribution of the rs3761548 FOXP3 polymorphism was analyzed separately in females and in males. The results demonstrated that females homozygous for the rare FOXP3 rs3761548 allele (A/A) are protected against AR; otherwise, females who are either wild types (C/C) or heterozygote carriers (C/A) of the rare allele are more susceptible to AR (OR [95%CI] = 2.089 [1,095; 3.988]). We were able to confirm the findings of Zhang et al. in a geographically and ethnically distinct population, the Hungarians, and revealed that the rs3761548 SNP is a marker of a haplotype in these two populations, but not in Sub-Saharan Africans, suggesting that this haplotype was fixed after early modern humans left Africa.

Signal peptide cleavage is essential for surface expression of a regulatory T cell surface protein, leucine rich repeat containing 32 (LRRC32).

BACKGROUND: Elevated numbers of regulatory T cells (T(regs)) have been implicated in certain cancers. Depletion of T(regs) has been shown to increase anti-tumor immunity. T(regs) also play a critical role in the suppression of autoimmune responses. The study of T(regs) has been hampered by a lack of adequate surface markers. Leucine Rich Repeat Containing 32 (LRRC32), also known as Glycoprotein A Repetitions Predominant (GARP), has been postulated as a novel surface marker of activated T(regs). However, there is limited information regarding the processing of LRRC32 or the regulatory phenotype and functional activity of T(regs) expressing LRRC32. RESULTS: Using naturally-occurring freshly isolated T(regs), we demonstrate that low levels of LRRC32 are present intracellularly prior to activation and that freshly isolated LRRC32+ T(regs) are distinct from LRRC32- T(regs) with respect to the expression of surface CD62L. Using LRRC32 transfectants of HEK cells, we demonstrate that the N-terminus of LRRC32 is cleaved prior to expression of the protein at the cell surface. Furthermore, we demonstrate using a construct containing a deleted putative signal peptide region that the presence of a signal peptide region is critical to cell surface expression of LRRC32. Finally, mixed lymphocyte assays demonstrate that LRRC32+ T(regs) are more potent suppressors than LRRC32- T(regs). CONCLUSIONS: A cleaved signal peptide site in LRRC32 is necessary for surface localization of native LRRC32 following activation of naturally-occurring freshly-isolated regulatory T cells. LRRC32 expression appears to alter the surface expression of activation markers of T cells such as CD62L. LRRC32 surface expression may be useful as a marker that selects for more potent T(reg) populations. In summary, understanding the processing and expression of LRRC32 may provide insight into the mechanism of action of T(regs) and the refinement of immunotherapeutic strategies aimed at targeting these cells.

Intranasal phototherapy is more effective than fexofenadine hydrochloride in the treatment of seasonal allergic rhinitis: results of a pilot study.

We recently showed that intranasal phototherapy represents an efficient therapeutic modality for the treatment of patients with seasonal allergic rhinitis (SAR). The aim of this pilot study was to compare the efficacy of intranasal phototherapy with that of the new generation antihistamine fexofenadine HCl in SAR. A randomized open study was conducted in patients with a history of moderate-to-severe ragweed-induced SAR. Thirty-one patients were randomly assigned to receive either intranasal irradiation three times a week for 2 weeks, or 180 mg fexofenadine HCl per day for 2 weeks. Each patient kept a diary of symptoms for nasal obstruction, nasal itching, rhinorrhea, sneezing and palate itching. Total nasal score (TNS), a sum of scores for nasal symptoms, was also calculated. In the rhinophototherapy group the individual scores significantly decreased compared with baseline for all of the parameters. In the fexofenadine HCl group none of the scores improved significantly at the end of the treatment except sneezing. TNS was significantly decreased in the rhinophototherapy group, but no significant change was observed in the fexofenadine HCl group after 2 weeks of treatment. In conclusion, we found that intranasal phototherapy is more efficient than fexofenadine HCl in reducing clinical symptoms for SAR.

[Empirical antibiotic therapy of complicated skin and soft tissue infections in dermatological practice]. / Komplikált bor- és lágyrész-fertozések empirikus antibiotikus terápiája a borgyógyászati gyakorlatban.

UNLABELLED: Erysipelas is an acute bacterial infection of the skin predominantly caused by Streptococcus pyogenes. According to the international classification complicated erysipelas belongs to the complicated skin and soft tissue infections. Complicated infections are defined as severe skin involvement or when the infection occurs in compromised hosts. These infections frequently involve Gram-negative bacilli and anaerobic bacteria. AIMS: The aim of this study was to compare the efficacy of the empirical antibiotic therapy for the patients who were admitted to the Department of Dermatology and Allergology, University of Szeged. METHODS: The empirical therapy was started according to a previously determined protocol. The data of 158 patients with complicated skin and soft tissue infections were analyzed and the microbiology culture specimens and the isolates were also examined. RESULTS AND CONCLUSIONS: The results show that penicillin is the first choice for the treatment of erysipelas. However, the complicated skin and soft tissue infections require broad-spectrum antibiotics.

Molecular response of nasal mucosa to therapeutic exposure to broad-band ultraviolet radiation.

Ultraviolet radiation (UVR) phototherapy is a promising new treatment for inflammatory airway diseases. However, the potential carcinogenic risks associated with this treatment are not well understood. UV-specific DNA photoproducts were used as biomarkers to address this issue. Radioimmunoassay was used to quantify cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts in DNA purified from two milieus: nasal mucosa samples from subjects exposed to intranasal phototherapy and human airway (EpiAirway) and human skin (EpiDerm) tissue models. Immunohistochemistry was used to detect CPD formation and persistence in human nasal biopsies and human tissue models. In subjects exposed to broadband ultraviolet radiation, DNA damage frequencies were determined prior to as well as immediately after treatment and at increasing times post-treatment. We observed significant levels of DNA damage immediately after treatment and efficient removal of the damage within a few days. No residual damage was observed in human subjects exposed to multiple UVB treatments several weeks after the last treatment. To better understand the molecular response of the nasal epithelium to DNA damage, parallel experiments were conducted in EpiAirway and EpiDerm model systems. Repair rates in these two tissues were very similar and comparable to that observed in human skin. The data suggest that the UV-induced DNA damage response of respiratory epithelia is very similar to that of the human epidermis and that nasal mucosa is able to efficiently repair UVB induced DNA damage.

Dysfunctional blood and target tissue CD4+CD25high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation.

The balance between regulatory and effector functions is important for maintaining efficient immune responses, while avoiding autoimmunity. The inflammatory skin disease psoriasis is sustained by the ongoing activation of pathogenic effector T cells. We found that a CD4(+) T lymphocyte subpopulation in peripheral blood, phenotypically CD25(high), CTLA-4(+), Foxp3(high) (regulatory T (Treg) cells), is deficient in its suppressor activity in psoriasis. This was associated with accelerated proliferation of CD4(+) responder T cells in psoriasis, the majority of which expressed CXCR3. Nevertheless, criss-cross experiments isolated the defect to psoriatic Treg cells. To examine Treg cells in a nonlymphoid tissue of a human T cell-mediated disease, Treg cells were also analyzed and isolated from the site of inflammation, psoriatic lesional skin. At the regulatory vs effector T cells ratios calculated to be present in skin, however, the psoriatic Treg cell population demonstrated decreased suppression of effector T cells. Thus, dysfunctional blood and target tissue CD4(+)CD25(high) Treg cell activity may lead to reduced restraint and consequent hyperproliferation of psoriatic pathogenic T cells in vivo. These findings represent a critical component of human organ-specific autoimmune disease and may have important implications with regard to the possible therapeutic manipulation of Treg cells in vivo.

Negative regulatory effect of histamine in DNFB-induced contact hypersensitivity.

Histamine plays an important role in the regulation of various immunological functions. To evaluate the role of histamine in contact hypersensitivity, contact dermatitis was induced with dinitrofluorobenzene (DNFB) in histidine decarboxylase knockout (HDC-/-) histamine-deficient and wild-type mice. The DNFB-induced increase of the ear thickness was significantly higher in HDC-/- mice than in wild-type mice. Using flow cytometry, significantly lower percentages of CD4+ Th and CD8+ Tc cells, and significantly higher percentages of CD45R+ B cells were observed in the regional lymph nodes in HDC-/- mice than in wild-type mice. In the ear specimens of both groups, the majority of the infiltrating cells were neutrophils and macrophages at 24 and 48 h after challenge. Using immunohistochemistry, we observed significantly more CD45+ leukocytes in HDC-/- mice than in wild-type mice. The expression of Th1 (IL-2, IFN-gamma, TNF-alpha) and Th2 (IL-4) mRNAs was examined by quantitative real time RT-PCR in the ear samples. The levels of Th1 cytokine mRNAs both at 24 and 48 h after challenge and IL-4 mRNA at 48 h showed a significantly higher increase in HDC-/- mice than in wild-type mice. These results suggest that histamine plays a negative immunoregulatory role in DNFB-induced contact hypersensitivity.