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Resumen Introduccion La urticaria por frio (UF) es un tipo de urticaria cronica inducible (CIndU) donde aparecen ronchas pruriginosas recurrentes y/o angioedema tras la exposicion a estimulos frios. Aunque normalmente solo afecta a areas expuestas, pueden producirse reacciones sistemicas. Nuestro objetivo es caracterizar los casos de UF de nuestro hospital. Material y metodos Estudio retrospectivo de casos de UF seguidos en nuestra consulta de urticaria en Portugal hasta octubre de 2020. Resultados Se incluyeron 52 pacientes, de ellos 40 mujeres. La edad media fue de 35 anos. En 19 pacientes, los sintomas comenzaron antes de los 18 anos de edad. La UF se clasifico como adquirida en todos los pacientes. Las pruebas de provocacion por frio fueron negativas en 9 pacientes, clasificados como UF atipica. No se encontraron diferencias con respecto al inicio en edad pediatrica o adulta. Mas de la mitad de los pacientes (52%) tenian una UF localizada. A pesar de no ser estadisticamente significativa, la temperatura umbral evaluada con TempTest® 4.0 fue mas alta y el tiempo de estimulacion mas corto en los pacientes con sintomas mas graves. Todos los pacientes fueron tratados con antihistaminicos y uno con omalizumab. Los pacientes controlados con dosis estandar de antihistaminicos tenian temperatura umbral mas baja que los que necesitaban dosis mas altas (p Conclusion La UF es una enfermedad heterogenea que, en algunos casos, puede poner en peligro la vida del paciente. Las pruebas de provocacion con frio pueden ser utiles en el manejo e identificacion de grupos de gravedad.

Summary Background. Chronic urticaria (CU) is a frequent disease, with a prevalence of at least 1%. It is characterized by pruritic wheals, angioedema or both for a period longer than 6 weeks. Objective. Identify the demographic, clinical, laboratory and therapeutic profile of patients treated in a Portuguese Urticaria Center of Reference and Excellence (UCARE) and compare it with international series. Methods. Retrospective analysis of database of patients observed in a specialized urticaria outpatient clinic, from January 2017 through September 2019, of a UCARE center in Portugal. Demographic and clinical features, laboratory findings and pharmacological treatment were obtained from the records. Descriptive analyses were performed for all variables. Chi square and fisher's exact tests were applied to analyze the independence of variables and the fit of distribution. P less than 0.05 was considered significant. Results. During this period, 477 patients were observed, of whom 429 (90%) were diagnosed with chronic urticaria. Mean age (years) at the onset of symptoms was 43.7 (standard deviation (SD) 17.6, range 6-88) and at diagnosis 46.7 (SD 17.8, range 6-88) resulting in an average diagnostic delay of 3 years (range 0-25). Median follow-up period since first attendance in the specialized outpatient clinic was 1.7 years (interquartile range (IQR) 0.79, range 0.1-2.75) . Concerning the whole group of CU patients, 347 (81%) had chronic spontaneous urticaria (CSU) - 79% female, 39 (9%) had isolated chronic inducible urticaria (CIndU) and 43 (10%) had CSU with CIndU. Autologous serum skin test (ASST) was done in 76 patients (positive in 24 (32%)) and basophil activation test (BAT) was done in 38 (positive in 13 (34%)). At the moment of study, 204 (48%) of CU patients were medicated with a second-generation H1-antihistamine (sgAH) daily (first-line therapy), 99 (23%) with sgAH up to four times the standard dose (second-line therapy) and 126 (29%) with omalizumab (third-line therapy). Additionally, 7 (2%) patients were completing a short course of systemic corticosteroids for management of disease exacerbation. Disease control was achieved in 316 of CSU patients (81%). Conclusions. Referral to a specialized urticaria outpatient clinic is important for a proper assessment of the disease and adequately symptom control.

Summary Introduction. Severe systemic reactions (SR) to allergen subcutaneous immunotherapy (SCIT) are rare but local reactions (LR) are common. We aimed to characterize the type of reactions and safety profile. Methods. Retrospective analysis of medical record from patients under SCIT between 2013-2016. Results. Total of 7372 SCIT injections in 323 patients: 52% female; mean age 30 years (SD 13); mean treatment time 19 months (SD 13). There were 57 patients (17.6% of population, 70% female) with at least one adverse reaction, for 93 reactions described (1.3% injections). There were 79 LR (1.1% injections) in 46(14.2%) patients: 36 in build-up, 43 in maintenance. There were 14 SR (0.19% injections) in 12(3.7%) patients: 12 in build-up, 2 in maintenance. All SR were grade 1. The majority of reactions were caused by mite SCIT (69.9%). Conclusions. SCIT is safe and well tolerated, with no report of SR grade > 1.

Carlos Romualdo Barbosa Gama,1 Manoel Antônio Gonçalves Pombo,1 Carlos Pereira Nunes,1 Gustavo Falcão Gama,1 Spyros GE Mezitis,2 Mendel Suchmacher Neto,3 Oscar Roberto Guimarães,1 Mauro Geller,1,4 Lisa Oliveira,4 Adenilson de Souza da Fonseca,1 Aline Sitnoveter,1 Gerson Goldwasser,3 Karin Soares Cunha,5 Luiz Guilherme Darrigo Junior6 1UNIFESO Medical School, Rio de Janeiro, Brazil; 2New York-Presbyterian Hospital/Weill-Cornell Medical Center, New York, NY, USA; 3Santa Casa de Misericórdia do Rio de Janeiro, Rio de Janeiro, Brazil; 4Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil; 5Pathology Department, Faculdade de Medicina - Universidade Federal Fluminense (UFF), Niterói, Brazil; 6Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, BrazilCorrespondence: Mauro Geller Av. Ataulfo de Paiva, 135 sl. 1104, Rio de Janeiro, RJ 22440-901, BrazilTel +55 21 3875-6660Fax + 55 21 2259-3395Email maurogeller@gmail.comPurpose: Urinary antiseptics including methenamine and methylene blue are used in the symptomatic treatment of urinary tract infections (UTIs).Patients and Methods: This was a prospective, double-blind, randomized, double-dummy safety and efficacy study of 2 urinary antiseptic combinations in the symptomatic treatment of recurrent cystitis: methenamine 120mg + methylene blue 20mg (Group A) versus acriflavine 15mg + methenamine 250mg + methylene blue 20mg + Atropa belladonna L. 15mg (Group B). All subjects underwent pretreatment urine culture and antibiotic sensitivity tests prior to 3-day oral treatment with study drug, followed by 3 days of antibiotic therapy (based on urine culture) + study drug treatment. Efficacy was evaluated using the Urinary Tract Infection Symptoms Assessment Questionnaire (UTISA). The primary endpoint was the percentage of patients presenting improvement in cystitis manifestations on the UTISA domain “Urination Regularity” at Visit 2. The primary safety variable was the incidence of treatment-related adverse events.Results: A total of 144 subjects were randomized per group and 272 completed the study. Primary endpoint analysis demonstrates homogeneity between treatment groups, with 69.4% and 72.2% subjects, respectively, showing improvement in the score of the urinary regularity UTISA domain after 3 days of treatment (p= 0.87). At Visit 2, incidence of treatment-related adverse events was higher in Group B (Group A: n= 11, Group B: n= 31, p= 0.0057).Conclusion: Both treatments were effective in reducing UTI symptoms assessed by UTISA questionnaire after 3 days of treatment. The two regimens were comparable in incidence of adverse events, but the combination of methenamine + methylene blue resulted in fewer treatment-related adverse effects.Keywords: urinary tract infection; UTI, urinary antiseptics, UTISA, methenamine, methylene blue

Introduction: Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant genetic disorders. Some clinical manifestations are present at birth, while some develop during childhood, and others can occur at any age. Given the early age at which patients develop clinical features, diagnosis is often made during childhood. The most prevalent features of NF1 are café au lait spots, dermal and plexiform neurofibromas, and learning disability. A variety of skeletal problems may be seen in NF1, including scoliosis, short stature, and pseudoarthrosis. Reduced skeletal bone mass has been documented to be a common phenomenon in children and adults with NF1. Decreased serum 25-hydroxyvitamin D (vitamin D) levels have been noted in adults and children with NF1 and have been reported to be inversely correlated with the number of dermal neurofibromas in adults. However, the actual correlation of vitamin D level to bone density and dermal neurofibroma number in children with NF1 remains unclear. Objectives: The primary objective of this study was to evaluate vitamin D levels among children and adolescents with NF1. The secondary objective was to describe the levels of vitamin D among children and adolescents with NF1, to verify in which age group there is a higher frequency of vitamin D alterations, and to explore vitamin D level correlations between age, gender, sun exposure, number of neurofibromas, and number of plexiform neurofibromas. Methods: This was an observational, cross-sectional, hospital-based study. We obtained a convenience sample of individuals with confirmed diagnosis of NF1 from patients attending the Medical Genetics Service of the IPPMG-UFRJ and Santa Casa de Misericórdia of Rio de Janeiro over a 24-month period. We evaluated vitamin D levels in blood samples of patients with NF1 by a chemiluminescent immunoassay method, and we correlated the results with gender, age, number of neurofibromas, number of plexiform neurofibromas, and satisfactory sun exposure. Results: Of the 55 patients, 28 (50.9%) were female and 27 (49.1%) were male. Patient ages ranged from a minimum of 1.2 to a maximum of 19.6 years (mean age 10.95 years) and the median was 11.11 years. Median and mean body mass index (BMI; z score) were -0.09 (minimum value -1.63 and maximum of 4.62) and 0.16, respectively. The mean value of vitamin D was 30.82 ng/mL (±12.31) and the median was 29 ng/mL (minimum value of 10.40 ng/mL and maximum of 79.19 ng/mL). Conclusions: The levels of vitamin D did not differ according to gender, age group, or the presence or number of cutaneous neurofibromas. Among patients with adequate sun exposure, there was a higher incidence of sufficient serum vitamin D levels. Patients with cutaneous neurofibromas in the 0 to 11 age group had a greater tendency to vitamin D sufficiency in relation to patients aged 11 to 19 years.

Background. Phlebotonics have beneficial effects on some symptoms related to chronic venous disease (CVD) of the lower limbs. The most commonly used one is diosmin, available in a pure semisynthetic form or as a micronized purified flavonoid fraction. Patients and Methods. The primary objective of this single-blind, randomized, parallel-group, prospective study was to assess the clinical noninferiority of nonmicronized diosmin 600 mg once daily (D-group) compared to micronized diosmin 900 mg plus hesperidin 100 mg once daily (D/H-group) over a 6-month treatment period. Adult patients with a symptomatic CVD of the lower limbs (C0-C3 grade; 20-60 mm on a 100 mm visual analog scale (VAS)) were included. The primary endpoint was the change (from baseline to last postbaseline value) of the intensity of the lower-limb symptoms on VAS. Results. 114 patients (mean age, 44.4 years; women, 90.4%) were randomized in the per-protocol analysis (D-group, n=57; D/H-group, n=57). Symptoms significantly improved in both groups with adjusted mean VAS changes of -24.9 mm (p<0.0001) in the D-group and -22.8 mm (p<0.0001) in the D/H-group, corresponding to approximately 50% reduction in basal symptom intensity. The difference between groups was -2.1 mm with an upper limit of one-sided 90% confidence interval equal to 1.0 mm for a noninferiority margin set at 20 mm (noninferiority demonstrated). Intent-to-treat analysis confirmed per-protocol analysis. Difficulty in swallowing the tablets (VAS) was significantly lower in the D-group compared to the D/H-group (9.4 mm and 54.7 mm at 6 months, respectively; p<0.0001). The overall safety of both study drugs was good. Conclusion. Nonmicronized diosmin 600 mg was proven to have a noninferior efficacy compared to micronized diosmin 900 mg plus hesperidin 100 mg, associated with greater ease in swallowing the tablet.

Rationale: In a previously published trial on spinal acute non-traumatic pain, peripheral neuro- regenerative combination of UTP, CMP and hydroxocobalamin presented unexpected analgesicproperties. Objective: To corroborate analgesiceffects of UTP, CMP and hydroxocobalamin combination in a self-paired evolutionary model. Methods: Mean VAS scores from pretreatment, V2 (5th treatment day) and V3 (10th treatment day) were plotted and statistically analyzed (ANOVA) for differences. PFQ scores from pretreatment, V2, and V3 were analyzed using the chisquare test. Results: The difference between V3 and pretreatment mean VAS scores was statistically significant (p < 0.0001). The improvement in PFQ scores throughout the study was found to be statistically significant (p < 0.0001). Conclusion: The combination of UTP, CMP and hydroxocobalamin seems to have analgesic properties in mediumterm use. The complex peripheral neu-roregenerative pharmacodynamics of this combination provides a plausible basis for this finding. Further randomized studies are needed to explore this combination for the indication of neuropathic pain due to spinal structure involvement.