Atopy in chronic urticaria: an important yet overlooked issue.

Chronic urticaria (CU) is one of the most common dermatological diseases and has a significant impact on the quality of life of patients. However, the pathogenesis of this disease remains unclear. Autoimmunity in chronic spontaneous urticaria (CSU) has received considerable attention and has been studied previously. Atopy is an important characteristic of CU; however, it has not been fully recognized. Atopy predisposes individuals to immune responses to allergens, leading to type 2 inflammation and immunoglobulin E (IgE) overproduction. Compared with healthy individuals, patients with CU have a higher proportion of atopy, and an atopic background is correlated with the clinical characteristics of CU. The total IgE levels in patients with CU is significantly higher than those in healthy individuals. Although its level is not higher than that in classic allergic diseases, it is closely related to CU. Exogenous allergens, auto-allergens, and specific IgEs, which are closely related to atopy, have been reported, and their roles in CU pathogenesis are also being studied. Local and systemic atopic inflammation is present in patients with CU. This review summarizes the current knowledge regarding atopy and CU, speculating that there are CU subtypes, such as atopic CSU or atopic chronic inducible urticaria (CIndU) and that atopy may be involved in the pathogenesis of CU. These findings provide a new perspective for a comprehensive understanding of the clinical features of CU and further research regarding its pathogenesis.

Biomarkers of Autologous Whole Blood Injection Efficacy in Patients with Chronic Spontaneous Urticaria with Autoreactivity: A Preliminary Study.

INTRODUCTION: Chronic spontaneous urticaria (CSU) with autoreactivity is often resistant to antihistamines. Autologous whole blood injection (AWBI) has shown potential efficacy in the treatment of this disease, but it is controversial. It is necessary to screen patients who are suitable for this therapy in advance. This study aimed to identify biomarkers that predict the efficacy of AWBI treatment in CSU patients with autoreactivity. METHODS: A total of 30 patients with autologous serum skin test-positive CSU treated with AWBI were included in this study; urticaria activity score (UAS7) was recorded and the treatment response was judged based on it. Levels of total serum IgE, anti-high-affinity IgE receptor (FcεRI) IgG, and basophils CD63 and FcεRI expressions, and D-dimer of all patients were determined and analyzed. RESULTS: Baseline levels of total IgE, D-dimer, basophil FcεRI and CD63 expressions showed good correlations with UAS7 variations. D-dimer, basophil FcεRI and CD63 expressions changed significantly before and after AWBI treatment in AWBI responders, and the basophil FcεRI and CD63 expressions consistently and dynamically decreased in AWBI responders during the treatment. Baseline levels of total IgE, D-dimer, basophil FcεRI and CD63 expressions showed certain predictive values for AWBI response. CONCLUSIONS: Baseline levels of total IgE, D-dimer, basophil FcεRI and CD63 expressions could be biomarkers of predicting AWBI efficacy in patients with CSU with autoreactivity.

Atopy Does Not Influence the Clinical Outcome of Acute Urticaria: A Retrospective Study.

BACKGROUND: Acute urticaria (AU) may be associated with atopy, but the relationship between atopic status and the clinical features of the disease has not been fully described. OBJECTIVES: The aim of the study was to determine the proportion of atopy in AU patients and to see whether atopy is related to the clinical characteristics of AU and whether it has an impact on the outcome of the disease. MATERIALS AND METHOD: A retrospective analysis of patients with AU was performed. Demographic data, clinical features, and laboratory results were compared and analyzed between the atopic and non-atopic AU (napAU). RESULTS: In total, 139 participants were included. 54 (38.8%) patients were atopic AU (apAU) and 85 (61.2%) were napAU. Compared with napAU patients, apAU patients were more likely to have anaphylaxis, higher levels of C4, and lower levels of antistreptolysin. There were no significant differences between the two groups in terms of other clinical features, laboratory tests, the natural course of the disease, or disease outcomes. CONCLUSION: Atopy does exist in some patients with AU, and AU patients with an atopic background are at higher risk for anaphylaxis. Atopy does not influence the clinical outcome of AU and is not correlated with other clinical features and laboratory results of AU.

Dupilumab and subcutaneous immunotherapy for the treatment of refractory moderate to severe atopic dermatitis: A preliminary report.

Subcutaneous immunotherapy (SCIT) and dupilumab are important treatments for patients with moderate to severe atopic dermatitis (AD). However, in clinical practice, poor response to allergen immunotherapy (AIT) or dupilumab has been observed in some patients. It is unknown whether combining dupilumab and SCIT can improve treatment responses in patients with moderate to severe AD that is resistant to dupilumab or SCIT monotherapy. This single-centre, retrospective, observational, real-world study evaluated the efficacy and safety of dupilumab and SCIT for refractory moderate to severe AD. The data of ten patients with moderate to severe atopic dermatitis who were treated with dupilumab and SCIT were retrospectively analysed. The scoring atopic dermatitis (SCORAD) score, numerical rating scale (NRS), and atopic dermatitis control test (ADCT) scores and eosinophil and total IgE levels before and after add-on therapy were compared and analysed. The SCORAD, NRS, and ADCT scores decreased significantly at four and 12 weeks after the initiation of add-on therapy and plateaued during maintenance treatment. The eosinophil and total IgE levels were not significantly different before and after add-on therapy. No serious adverse reactions were reported in any patient during add-on therapy. This study indicates that the combination of dupilumab and SCIT safely improves the treatment response of patients with moderate to severe AD who are resistant to dupilumab or SCIT monotherapy.

The Roles of Microtubule-Associated Protein 4 in Wound Healing and Human Diseases.

Microtubules (MTs) are essential structural elements of cells. MT stability and dynamics play key roles in integrity of cell morphology and various cellular activities. The MT-associated proteins (MAPs) are specialized proteins that interact with MT and induce MT assemble into distinct arrays. Microtubule-associated protein 4 (MAP4), a member of MAPs family, ubiquitously expressed in both neuronal and non-neuronal cells and tissues, plays a key role in regulating MT stability. Over the past 40 years or so, the mechanism of MAP4 regulating MT stability has been well studied. In recent years, more and more studies have found that MAP4 affects the activities of sundry human cells through regulating MT stability with different signaling pathways, plays important roles in the pathogenesis of a number of disorders. The aim of this review is to outline the detailed regulatory mechanisms of MAP4 in MT stability, and to focus on its specific mechanisms in wound healing and various human diseases, thus to highlight the possibility of MAP4 as a future therapeutic target for accelerating wound healing and treating other disorders.

Symptomatic dermographism induced by oral minocycline: A report of four cases.

Symptomatic dermographism (SD) is the most common form of chronic inducible urticarias. The etiology of this disease has rarely been reported in the literature. Minocycline is widely used in the treatment of acne, rosacea, and other inflammatory skin diseases. Herein we report four cases of SD onset during minocycline administration. These were young women in their 20s to 30s who were taking minocycline orally for acne vulgaris or rosacea. They all experienced the onset of SD 2-3 weeks after taking the drug, and then the complete disappearance of SD 1 month after stopping the drug. Minocycline was thought to be the culprit drug in these cases as other drugs were ruled out on clinical grounds. Our small series suggests that oral minocycline may induce SD, thus raising the awareness of this association in clinical practice. More research is needed to further confirm this association and reveal the underlying mechanism(s).

Severe Herpes Zoster Secondary to Systemic Lupus Erythematosus Successfully Treated with Ultraviolet A1 Phototherapy: A Case Report.

Background: The incidence of herpes zoster (HZ) in systemic lupus erythematosus (SLE) patients is high, and the symptoms are usually severe and resistant to treatment, and the prognosis is poor. Ultraviolet (UV) A1 is a band of UV light, and UVA1 phototherapy has been widely used to treat various inflammatory skin diseases. Objective: At present, UVA1 has been considered as a potential adjuvant therapy for HZ in SLE patients. To the best of our knowledge, this is the first case report concerning the successful application of UVA1 in the treatment of HZ secondary to SLE. Methods: In this article, a clinical case report is presented, wherein the patient did not respond to conventional treatment, but was markedly responsive to the treatment of UVA1 phototherapy, and well tolerated. Results: A 29-year-old woman with severe HZ secondary to SLE was successfully treated with UVA1 phototherapy. Conclusions: UVA1 phototherapy can be used as an effective adjuvant treatment for HZ secondary to SLE.

Chronic Non-Healing Ulcers Associated with Atopic Inflammation: A Case Report.

Chronic non-healing ulcers are the undesirable outcome of delayed wound healing influenced by many factors. It can be seen in patients with diabetes, autoimmune conditions and multiple primary skin conditions. But chronic non-healing ulcers secondary to atopic inflammation are rarely reported in the literature. In this study, we reported a case with wounds caused by the wrong tattoo and surgery, activation of atopic inflammation caused delayed wound healing and the formation of chronic non-healing ulcers. The patient's atopic inflammation was relieved and stabilized with oral cyclosporine and topical application of halometasone cream and subsequently 0.1% tacrolimus cream, and then the chronic non-healing ulcers healed well, without recurrence at a follow-up visit 3 months later.

Carvedilol ameliorates persistent erythema of erythematotelangiectatic rosacea by regulating the status of anxiety/depression.

The treatment of persistent erythema and rosacea flushing is extremely challenging, especially for patients with anxiety. The aim of this study was to verify the efficacy of carvedilol in rosacea patients with persistent erythema and flushing. A total of 156 patients were randomized to use oral carvedilol 5 mg bid (twice per day) (n = 105) or topical brimonidine (n = 51) for a 10-week period with 6 weeks of follow-up. Both the efficacy of carvedilol and the status of anxiety/depression were analyzed by patient self-assessment (PSA), clinician erythema assessment (CEA), generalized anxiety disorder (GAD-7), and patient health questionnaire-9 (PHQ-9). Our study found that carvedilol exerted a dramatic reduction in CEA/PSA scores and sting/burning sensation scores in comparison to topical brimonidine. Additionally, carvedilol treatment dramatically improved telangiectasia, erythema, and pigmentation with no obvious side effects. Patients with carvedilol treatment showed an improvement of depression/anxiety, as reflected by lower GAD-7 and PHQ-9 scores than patients with topical brimonidine. Notably, we found carvedilol treatment had better outcomes among patients under 30 years of age with rosacea younger than 30 years old. Conclusively, our findings reveal that carvedilol could quickly and effectively improve facial erythema, which might stem from the improved the status of anxiety/depression.

Efficacy and safety of ebastine dose escalation in chronic urticaria: A prospective study.

The second-generation antihistamines at licensed doses are first-line treatment in urticaria and up-dosing is recommended as second-line treatment. To assess the efficacy and safety of escalated doses of ebastine in patients with chronic urticaria (CU), we designed this study. Recruited patients with CU were treated with increasing doses of ebstine. Treatment started at the daily dose of 10 mg. The symptom is assessed weekly, and if there is no significant improvement, the dose is increased from 10 mg to 20 mg, and if still no significant improvement, up to 40 mg. Pruritus, number, diameter, duration and frequency of wheals, and adverse reactions were assessed. One hundred and forty (76.50%) patients achieved marked effect with ebastine 10 mg/day, 27 (14.75%) patients with ebastine 20 mg/day and 13 (7.10%) patients with ebastine 40 mg/day, while 3(1.64%) patients did not get marked effect. There was no significant difference of effect between factitious urticaria, CSU, cholinergic urticaria and CSU with factitious urticaria in different dose (all p > 0.05). Common adverse reactions of ebstine treatment, included dry mouth, somnolence, tiredness and headache, were mild or moderate. There was no significant difference between the degree score of dry mouth with different doses of ebastine, and the same to somnolence, tiredness and headache (all p > 0.05). Doses escalation of ebastine should be effective in treatment of factitious urticaria, CSU and cholinergic urticaria with poorly treated by standard of double doses. Increasing ebastine dose did not increase the incidence of adverse reactions.

Pathogenic role of circulating CD4+CXCR5+ cell subpopulations in patients with chronic spontaneous urticarial.

Accumulating evidence demonstrated that circulating CD4+CXCR5+, follicular helper T (Tfh) and follicular regulatory T (Tfr) cells maintain immune homeostasis and humoral immune response and were involved in the pathogenesis of certain autoimmune/inflammatory diseases. The current study was aimed to investigate the correlation between frequencies of CD4+CXCR5+, Tfh and Tfr cells, Tfh/Tfr and the disease activity in chronic spontaneous urticaria (CSU). Frequencies of CD4+CXCR5+, Tfh and Tfh/Tfr, but not Tfr, in peripheral blood mononuclear cells (PBMCs) were elevated in patients with CSU as compared with healthy controls. No difference was observed in the frequency of these cells between different subgroups of patients based on autologous serum skin testing (ASST), skin prick testing (SPT) and the level of total IgE. The expression of CXCR5 in PBMCs was higher in CSU than in controls, both at mRNA and protein levels. Higher levels of plasma IL-4, IL-6 and total IgE were observed in CSU, with positive correlation between IL-4/IL-6 and total IgE. The IL-21 level was lower and negatively correlated with total IgE. Using receiver operating characteristic (ROC) curve, we found positive correlation between the urticaria activity score (UAS) and CD4+CXCR5+, Tfh, Tfh/Tfr and total IgE, respectively, with area under the curves (AUCs) all greater than 0.7 (P < 0.05). These results indicated that frequencies of circulating CD4+CXCR5+ cells, Tfh cells and Tfh/Tfr were abnormal and correlated positively with disease severity, suggesting the possible involvement of these cells in the immunopathogenesis of CSU.

Cutaneous tuberculosis: A great imitator.

Tuberculosis (TB) is still prevalent in many developing countries and can pose a new potential threat to global health due to international migration. As an uncommon form of extrapulmonary TB, cutaneous TB is complicated in its clinical manifestation, pathogenesis, and classification. Cutaneous TB can be divided into two major categories, true cutaneous TB and tuberculid, depending on the source of infection, the route of transmission, the amount of bacteria, and the immune state of the host. Clinical manifestations may include patches and plaques (lupus vulgaris, TB verrucosa cutis), macules and papules (acute miliary TB, papulonecrotid tuberculid, lichen scrofulosorum), nodules, and abscesses (erythema induratum of Bazin, tuberculous gumma), erosions, and ulcers (tuberculous chancre, orificial TB, scrofuloderma), mimicking diverse skin diseases. Uncommon localizations such as external genitalia, unusual presentations such as nodular granulomatous phlebitis, and coexistence with other morbidities such as Behçet disease and acne inversa or hidradenitis suppurativa deserve special attention. Treatment of both true and tuberculid cutaneous TB follows the same drug regimens of the World Health Organization's recommendation for treatment of new cases of pulmonary TB. Erythema induratum of Bazin may need longer treatment duration and adjuvants such as dapsone, potassium iodide, doxycycline, and corticosteroids to tackle inflammation. Misdiagnosis and undertreatment in daily practice are likely, and contemplation of this classic great imitator in dermatology is warranted.

Bacteremia in female Chinese patients with systemic lupus erythematosus: a case-control study.

INTRODUCTION: Bacteremia is a common complication in systemic lupus erythematosus (SLE) patients, causing high morbidity and mortality. We investigated characteristics, pathogens, and sites of infection using a cohort of 64 female adults from a single university hospital in China. METHODOLOGY: SLE patients who had at least one episode of bacteremia (n = 16) were compared with non-bacteremia SLE patients (n = 48) in a case-control fashion, matching for age at SLE diagnosis and time of admission. Demographic characteristics, clinical and laboratory data, and bacteriologic examinations were collected and reviewed. RESULTS: A series of parameters were found to be significantly different between controls and cases at bacteremia diagnosis, including an SLE disease activity index, multiple major organ involvement (> 2), active renal disease, leukocytes, neutrophils, 24-hour urine protein, erythrocyte sedimentation rate (ESR), aspartate aminotransferase (AST), creatinine, hemoglobin, lymphocyte, platelets, and albumin. Eighteen episodes of bacteremia were analyzed, with Escherichia coli and Staphylococcus aureus being the most frequent isolates. Additionally, Listeria monocytogenes, Rhodotorula mucilaginosa, and Salmonella choleraesuis, which were very rare in the general population, were isolated from the bloodstreams of the cases. Apart from bacteremia without focus, respiratory tract, gastrointestinal tract, urinary tract, skin, and soft tissue were the major origins of infection. CONCLUSIONS: The present study depicts the nature of a cohort of female Chinese SLE patients with bacteremia, revealing that bacteremia is a critical factor contributing to the aggravation of SLE. Our findings provide useful information regarding the control and prevention of bacteremia in female SLE patients in China.

Current Advances in 5-Aminolevulinic Acid Mediated Photodynamic Therapy.

Kennedy and Pottier discovered that photodynamic therapy (PDT) could be carried out using a procedure consisting of topical application of the porphyrin-precursor, 5-aminolevulinic acid (ALA) to the skin, followed after some time by illumination with various light parameters in the 1980s. Since then, ALA-PDT has expanded enormously and now covers most aspects of dermatological disease. The purpose of this review is to discuss a range of ingenious strategies that investigators have devised for improving the overall outcome (higher efficiency and lower side effects) of ALA-PDT. The big advance of using ALA esters instead of the free acid to improve skin penetration was conceived in the 1990s. A variety of more recent innovative approaches can be divided into three broad groups: (a) those relying on improving delivery or penetration of ALA into the skin; (b) those relying on ways to increase the synthesis of protoporphyrin IX inside the skin; (c) those relying on modification of the illumination parameters. In the first group, we have improved delivery of ALA with penetration-enhancing chemicals, iontophoresis, intracutaneous injection, or fractionated laser. There is also a large group of nanotechnology-related approaches with ALA being delivered using liposomes/ethosomes, ALA dendrimers, niosomes, mesoporous silica nanoparticles, conjugated gold nanoparticles, polymer nanoparticles, fullerene nanoparticles, and carbon nanotubes. In the second group, we can find the use of cellular differentiating agents, the use of iron chelators, and the effect of increasing the temperature. In the third group, we find methods designed to reduce pain as well as improve efficiency including fractionated light, daylight PDT, and wearable light sources for ambulatory PDT. This active area of research is expected to continue to provide a range of intriguing possibilities.

[Study on the prevalence rate of rheumatoid arthritis in Zhuang nationality population from Nanning, Guangxi].

OBJECTIVE: To study the prevalence rate of rheumatoid arthritis in Zhuang nationality population of Nanning, Guangxi. METHODS: A total of 7407 people with Zhuang nationality, aged 16 and over were surveyed. Questionnaire was administered to each subject under survey, while X-ray and serum rheumatoid factor were carried out to all those who gave positive answers. Physical examinations were done to the suspicious cases by experts on rheumatism. RESULTS: were compared with those in 6826 people of Han ethnicity living in the same district. RESULTS: The prevalence rates of rheumatoid arthritis in Zhuang nationality population was 0.27% when comparing to the Han population which was 0.28% (P > 0.05). Rates of awareness on rheumatoid arthritis in Zhuang and Han population were 5.0% and 10.5% (P > 0.05). After the diagnosis of rheumatoid arthritis was made and among patients who had received the treatment, the rates were 0% vs. 5.25%. CONCLUSION: The prevalence rate of rheumatoid arthritis in Zhuang nationality population of Nanning, Guangxi was not significantly different than that in Han ethnic group. However, the rates on awareness and the treatment of rheumatoid arthritis were still under satisfaction.