Chronic urticaria (CU) is a widespread skin disease, characterized by the recurrence of transient wheals and itch for more than 6 weeks. Besides autoimmune mechanisms, coagulation factors, in particular tissue factor and thrombin, might also participate in the disease pathophysiology. Tissue factor expressed by eosinophils can induce activation of blood coagulation generating thrombin which in turn can increase vascular permeability both directly, acting on endothelial cells, and indirectly, inducing degranulation of mast cells with release of histamine, as demonstrated in experimental models. D-dimer, a fibrin degradation product, generated following activation of the coagulation cascade and fibrinolysis, has been found to be increased during urticaria exacerbations; moreover, it has been proposed as a biomarker of severity and resistance to H1-antihistamines in CU patients. The possible role of coagulation in CU is also supported by case reports, case series and a small controlled study showing the efficacy of anticoagulant therapy in this disease. The purpose of this review was to summarize the available data on the possible contribution of coagulation to the pathophysiology of CU focusing on clinical aspects and possible future therapeutic developments.Chronic urticaria (CU) is a widespread skin disease characterized by the recurrence of transient wheals and itch for more than 6 weeks. It is believed that over 50% of CU cases are accompanied by a deep subcutaneous and/or submucosal edema, called angioedema (AE; 1).It is well known that the characteristic symptoms of urticaria appear following the activation of mast cells (MCs) and basophils in the skin by various stimuli. These cells release several biologically active substances, the most important of which is histamine. Histamine induces vasodilation, increases vascular permeability and stimulates sensory nerve endings. These effects lead to the appearance of erythema, wheals and itch (2). It is supposed that other biologically active substances may have similar effects. These include serotonin, C3a and C5a anaphylatoxins, platelet-activating factor (PAF), neuropeptides, and arachidonic acid metabolites (prostaglandin D2, leukotrienes C4, D4 and E4; 3).Activation and degranulation of basophils and MCs may occur by immunological (formation of immune complexes, complement activation, IgE cross-linking), nonimmunological (pseudoallergy, infection, or direct effect of agents on MCs), or mixed mechanisms. The mechanism and cause of urticaria remain unclear in many patients with CU.In recent years, attention was paid to several important aspects of the disease pathogenesis. It is believed that about 30-50% of patients have CU symptoms associated with autoimmune reactions and synthesis of autoantibodies against IgE (4) and/or the FceRI a-subunit on MCs and basophils (autoimmune/autoreactive urticaria; 5). Furthermore, these patients show an increased frequency of HLA DRB1*04 (DR4) as it occurs in other autoimmune diseases (6). The role of coagulation casc...

Chronic spontaneous urticaria (CSU) is defined as persistent wheals, angioedema, or both lasting for >6 weeks due to known or unknown causes. Some epidemiological studies and case reports suggest that internal parasite infections (PI) can cause CSU. Here, we provide a systematic overview of published findings on the prevalence and relevance of PI in CSU and we discuss possible pathomechanisms. The prevalence of PI in CSU was investigated by 39 independent studies and comorbidity reportedly ranged from 0 to 75.4% (two-thirds of these studies reported infection rates of 10% or less). The prevalence of PI in adult and pediatric CSU patients ranged from 0% to 75.4% and from 0% to 37.8%, respectively. CSU patients were more often diagnosed with protozoa and had a significantly higher risk of toxocariasis seropositivity and Anisakis simplex sensitization when compared to healthy controls. Patients with chronic urticaria more frequently had seropositivity of fasciolosis, Anisakis simplex sensitization, and the presence of Blastocystis hominis allele 34 (ST3) as compared with control subjects. In 21 studies, efficacy of treatment with antiparasitic drugs ranged from 0 to 100% (35.7% of 269 CSU patients benefitted). In 9 (42.8%) of 21 studies, more than 50% of efficacy was observed. The reported rate of urticaria comorbidity in PI patients in 18 independent studies is 1-66.7%. Urticaria including CSU might be a quite common symptom of strongyloidiasis and blastocystosis. Pathogenic mechanisms in CSU due to PI may include specific IgE, Th2 cytokine skewing, eosinophils, activation of the complement, and the coagulation systems.Chronic spontaneous urticaria (CSU) is defined as the recurrent development of transient wheals (hives), angioedema (AE), or both for >6 weeks due to known or unknown causes (1). The prevalence of CSU in the general population has been estimated to range from 0.5% to 5% (1, 2). In up to 90% of CSU cases, the search for underlying causes is not successful, in routine clinical practice (1-3). Autoimmunity, food intolerance, and infections, including internal parasitic infections (PI), have been described as underlying causes of CSU (1, 4). A possible role for PI in urticaria was suggested as early as in 1949 (5): in a 16-year-old boy with Giardia lamblia and CSU. His CSU resolved completely after specific and effective treatment of the infection. Since then, infections with endoparasites, such as helminths (worms, which consist of many cells and have internal organs) and protozoa (consist of only one cell), have been discussed to cause chronic urticaria, and several clinical studies and reviews on the prevalence and relevance of PI in patients with CSU were performed and published (4,(6)(7)(8)(9)(10).Parasites are more prevalent in equatorial regions and countries with a tropical climate, high humidity, poor sanitation, dirty water, substandard and crowded housing, and in populations with low socioeconomic status (sub-Saharan Africa, Asia, Latin America, and Caribbean) (11,12). According to a ...

Chronic spontaneous urticaria (CSU) is a common mast cell-driven disease characterized by the development of wheals (hives), angioedema (AE), or both for > 6 weeks. It is thought that autoimmunity is a common cause of CSU, which is often associated with autoimmune thyroiditis, whereas the link to other autoimmune disorders such as systemic lupus erythematosus (SLE) has not been carefully explored. Here, we systematically reviewed the existing literature for information on the prevalence of CSU in SLE (and vice versa) and we examined the possible clinical and pathogenetic relationship between CSU and SLE. The prevalence of CSU and CSU-like rash in SLE was investigated by 42 independent studies and comorbidity in adult patients reportedly ranged from 0% to 21.9% and 0.4% to 27.5%, respectively (urticarial vasculitis: 0-20%). In children with SLE, CSU was reported in 0-1.2% and CSU-like rash in 4.5-12% (urticarial vasculitis: 0-2.2%). In contrast, little information is available on the prevalence of SLE in patients with CSU, and more studies are needed to determine the rate of comorbidity. Recent insights on IgG- and IgE-mediated autoreactivity suggest similarities in the pathogenesis of CSU and SLE linking inflammation and autoimmunity with the activation of the complement and coagulation system. Future studies of patients with either or both conditions could help to better define common pathomechanisms in CSU and SLE and to develop novel targeted treatment options for patients with CSU and SLE.

In acne vulgaris, antimicrobial peptides (AMPs) could play a dual role; i.e., protective by acting against Propionibacterium acnes, pro-inflammatory by acting as signalling molecules. The cutaneous expression of 15 different AMPs was investigated in acne patients; furthermore, the impact of isotretinoin therapy on AMP expression was analysed in skin biopsies from 13 patients with acne vulgaris taken before, during and after a 6-month treatment cycle with isotretinoin using quantitative real-time polymerase chain reaction. Cutaneous expression of the AMPs cathelicidin, human β-defensin-2 (HBD-2), lactoferrin, lysozyme, psoriasin (S100A7), koebnerisin (S100A15), and RNase 7 was upregulated in untreated acne vulgaris, whereas α-defensin-1 (HNP-1) was downregulated compared to controls. While relative expression levels of cathelicidin, HBD-2, lactoferrin, psoriasin (S100A7), and koebnerisin (S100A15) decreased during isotretinoin treatment, only those of cathelicidin and koebnerisin returned to normal after 6 months of isotretinoin therapy. The increased expression of lysozyme and RNase 7 remained unaffected by isotretinoin treatment. The levels of granulysin, RANTES (CCL5), perforin, CXCL9, substance P, chromogranin B, and dermcidin were not regulated in untreated acne patients and isotretinoin had no effect on these AMPs. In conclusion, the expression of various AMPs is altered in acne vulgaris. Isotretinoin therapy normalizes the cutaneous production of distinct AMPs while the expression of others is still increased in healing acne. Considering the antimicrobial and pro-inflammatory role of AMPs, these molecules could serve as specific targets for acne therapy and maintenance of clinical remission.

Coronavirus (SARS-CoV-2; COVID-19) has dramatically spread throughout the world despite extraordinarily restricted measures performed by all countries. Global cases of COVID-19 have passed the 4.5 million checkpoint, and Russia is currently ranked the second most infected nation in the world with 252 245 confirmed cases and 2305 deaths. Approximately 65% of patients are under the age of 65 and