Subject(s)
Chronic Urticaria/drug therapy , Histamine H1 Antagonists/therapeutic use , Immunosuppressive Agents/therapeutic use , Methotrexate/therapeutic use , Adult , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Immunosuppressive Agents/adverse effects , Male , Methotrexate/adverse effects , Middle Aged , Quality of LifeSubject(s)
Acute Generalized Exanthematous Pustulosis/etiology , Contrast Media/adverse effects , Iohexol/analogs & derivatives , Iopamidol/analogs & derivatives , Acute Generalized Exanthematous Pustulosis/pathology , Acute Generalized Exanthematous Pustulosis/prevention & control , Adrenal Cortex Hormones/therapeutic use , Aged, 80 and over , Cross Reactions , Humans , Iohexol/adverse effects , Iopamidol/adverse effects , Male , Patch Tests , Premedication , Severity of Illness IndexABSTRACT
Strategies for diets in chronic spontaneous urticaria (CSU) are controversial. This systematic review assessed the interest in diet for managing CSU. We searched for original reports in MEDLINE, EMBASE, CENTRAL and LILACS. Among the 278 reports screened, 20 were included, involving 1,734 patients. Reports described 3 types of systematic diet: pseudoallergen-free diet (n = 1,555 patients), low-histamine diet (n = 223) and diet without fish products (n = 47), which induced complete remission in 4.8%, 11.7% and 10.6% of patients, respectively, and partial remission in 37.0%, 43.9% and 4.3%. Eight reports described personalized exclusion diets (66 patients) adapted to symptoms/allergological test results and led to complete remission in 74.6% of patients, although the diagnosis of CSU was doubtful. No comparative randomized studies of diets were available. The only randomized studies were based on oral provocation tests with the suspected responsible diet. Population and outcomes were heterogeneous. In conclusion, there is evidence for the benefit of diets in CSU only in individual patients with clinical symptoms. However, the level of evidence is low for the benefit of systematic diets in CSU because systematic double-blind controlled trials of diet are lacking.
Subject(s)
Diet/adverse effects , Urticaria/diet therapy , Allergens/adverse effects , Chronic Disease , Fish Products/adverse effects , Histamine/adverse effects , Humans , Remission Induction , Risk Factors , Treatment Outcome , Urticaria/diagnosis , Urticaria/immunologyABSTRACT
Membrane-bound proteinase 3 (PR3m) is the main target antigen of anti-neutrophil cytoplasmic autoantibodies (ANCA) in granulomatosis with polyangiitis, a systemic small-vessel vasculitis. Binding of ANCA to PR3m triggers neutrophil activation with the secretion of enzymatically active PR3 and related neutrophil serine proteases, thereby contributing to vascular damage. PR3 and related proteases are activated from pro-forms by the lysosomal cysteine protease cathepsin C (CatC) during neutrophil maturation. We hypothesized that pharmacological inhibition of CatC provides an effective measure to reduce PR3m and therefore has implications as a novel therapeutic approach in granulomatosis with polyangiitis. We first studied neutrophilic PR3 from 24 patients with Papillon-Lefèvre syndrome (PLS), a genetic form of CatC deficiency. PLS neutrophil lysates showed a largely reduced but still detectable (0.5-4%) PR3 activity when compared with healthy control cells. Despite extremely low levels of cellular PR3, the amount of constitutive PR3m expressed on the surface of quiescent neutrophils and the typical bimodal membrane distribution pattern were similar to what was observed in healthy neutrophils. However, following cell activation, there was no significant increase in the total amount of PR3m on PLS neutrophils, whereas the total amount of PR3m on healthy neutrophils was significantly increased. We then explored the effect of pharmacological CatC inhibition on PR3 stability in normal neutrophils using a potent cell-permeable CatC inhibitor and a CD34+ hematopoietic stem cell model. Human CD34+ hematopoietic stem cells were treated with the inhibitor during neutrophil differentiation over 10 days. We observed strong reductions in PR3m, cellular PR3 protein, and proteolytic PR3 activity, whereas neutrophil differentiation was not compromised.
Subject(s)
Cathepsin C/antagonists & inhibitors , Cell Membrane/metabolism , Cysteine Proteinase Inhibitors/pharmacology , Granulomatosis with Polyangiitis/pathology , Myeloblastin/metabolism , Adolescent , Adult , Case-Control Studies , Child , Child, Preschool , Female , Granulomatosis with Polyangiitis/drug therapy , Granulomatosis with Polyangiitis/genetics , Granulomatosis with Polyangiitis/metabolism , Humans , Male , Myeloblastin/genetics , Neutrophils/enzymology , Proteolysis , Young AdultSubject(s)
Erythema/diagnosis , Skin Diseases, Vesiculobullous/diagnosis , Skin Diseases/diagnosis , Skin/pathology , Administration, Cutaneous , Adolescent , Dermatologic Agents/administration & dosage , Erythema/drug therapy , Erythema/pathology , Humans , Male , Neck , Nicotinic Acids/administration & dosage , Skin/drug effects , Skin Diseases/drug therapy , Skin Diseases/pathology , Skin Diseases, Vesiculobullous/drug therapy , Skin Diseases, Vesiculobullous/pathology , Treatment OutcomeABSTRACT
BACKGROUND: Chronic spontaneous urticaria (CSU) is not frequent in children. Management guidelines have been developed for adults and randomized controlled trials (RCTs) included teenagers aged 12-18, but data for children under age 12 are limited. We performed a systematic review to assess comorbidities in children <12 years old with CSU and the efficacy and safety of treatments. METHODS: We searched for original articles of epidemiologic and treatment data in children <12 years old with CSU that were published from 2005 to July 2016 in MEDLINE, EMBASE, CENTRAL, and LILACS. Article selection and data extraction were performed in duplicate. RESULTS: Our systematic review included 9 reports on epidemiologic data (633 children). Five comorbidities and laboratory anomalies associated with CSU found were atopy (28.1%), positive autologous serum skin test (36.8%), thyroid biologic anomalies (6.4%) and detectable antinuclear antigen (10.4%), seroprevalence for Helicobacter pylori (21.1%), low vitamin D level (69.1%), and psychiatric disorders (70.4%). Only one study allowed for comparison with a control group. Our review included 10 studies (322 children), describing 5 different drug families, mostly H1-antihistamines (n = 297). One randomized controlled study compared single-dose rupatadine with single-dose desloratadine and placebo. Cyclosporine was effective and had no adverse effects in 18 children. Omalizumab, montelukast, and cefuroxime were reported in very small series (5, 1, and 1 patients). CONCLUSIONS: H1-antihistamines are effective for CSU in children <12 years old, with reassuring safety data at licensed doses. Cyclosporine seems effective, but the level of evidence is low.