Características del síndrome inflamatorio multisistémico asociado a COVID-19 en niños atendidos en un hospital peruano, 2020-2022 / Characteristics of COVID-19-associated multisystemic inflammatory syndrome in children treated in a Peruvian hospital, 2020-2022

RESUMEN El propósito del estudio fue describir las características del síndrome inflamatorio multisistémico asociado a COVID-19 (SIM-C) en los primeros tres años de pandemia en niños de un hospital pediátrico del Perú. Se realizó un estudio observacional, descriptivo con datos de 73 pacientes y se describieron las características clínicas, laboratoriales, tratamiento y complicaciones según la ola de la pandemia y si tuvieron shock. La mediana de edad fue 6 años, las manifestaciones gastrointestinales y mucocutáneas fueron frecuentes en las tres olas. El fenotipo similar a enfermedad de Kawasaki se presentó en 34 (46,6%) pacientes y 21 (28,8%) pacientes desarrollaron shock. El tratamiento más usado fue la inmunoglobulina (95,9%), ácido acetil salicílico (94,5%) y corticoide (86,3%). Cinco (7%) pacientes tuvieron aneurisma coronario y 17 (23,3%) ingresaron a la unidad de cuidados intensivos (UCI). Los pacientes con shock tuvieron mayor alteración laboratorial y necesidad de ventilación mecánica. En conclusión, el SIM-C ha disminuido en los primeros tres años de pandemia posiblemente por la vacunación de COVID-19 en niños.

ABSTRACT This study aimed to describe the characteristics of multisystemic inflammatory syndrome associated with COVID-19 (MIS-C) in the first three years of the pandemic in children in a pediatric hospital in Peru. We conducted an observational, descriptive study with data from 73 patients and described the clinical and laboratory characteristics, treatment and complications according to the wave of the pandemic and whether they had shock. The median age was 6 years, gastrointestinal and mucocutaneous manifestations were frequent in the three waves. Kawasaki disease-like phenotype was present in 34 (46.6%) patients and 21 (28.8%) patients developed shock. The most commonly used treatment was immunoglobulin (95.9%), followed by acetylsalicylic acid (94.5%) and corticosteroid (86.3%). Five (7%) patients had coronary aneurysm and 17 (23.3%) were admitted to the intensive care unit (ICU). Patients with shock had greater laboratorial alteration and need for mechanical ventilation. In conclusion, MIS-C has decreased in the first three years of the pandemic, possibly due to COVID-19 vaccination in children.

Case Report: C3 deficiency in two siblings.

The complement system, a vital component of innate immunity, consists of various proteins and pathways crucial for the recognition and elimination of pathogens. In addition, it plays a major role in the initiation of adaptive response through the opsonization of antigens, contributing to B-cell activation and memory maintenance. Deficiencies in complement proteins, particularly C3, can lead to severe and recurrent infections as well as immune complex disorders. Here, we present a case report of two siblings with total C3 deficiency resulting from compound heterozygous mutations in C3 (NM_000064.4): c.305dup; [p.Asn103GlnfsTer66] and c.1269 + 5G>T, previously unreported in C3-related diseases. Both, the index case and her sister, presented a history of recurrent infections since early childhood and one of them developed hemolytic uremic syndrome (HUS). Immunological evaluation revealed absent plasma C3 levels, decreased memory B cells, hypogammaglobulinemia, and impaired response to polysaccharide antigens. The siblings showed partial responses to antimicrobial prophylaxis and vaccination, requiring intravenous immunoglobulin replacement therapy, resulting in clinical improvement. Genetic analysis identified additional risk polymorphisms associated with atypical HUS. This case highlights the importance of comprehensive genetic and immunological evaluations in complement deficiencies, along with the potential role of immunoglobulin replacement therapy in managing associated antibody defects.

Effect of intravenous immunoglobulin on the management of Rh- and ABO-mediated hemolytic disease of the newborn.

BACKGROUND: Regarding the close association between neonatal hyperbilirubinemia and occurrence of pathological jaundice as a cause of neurotoxicity and kernicterus, the present study aimed to evaluate the use of intravenous immunoglobulin (IVIG) in neonates with hyperbilirubinemia. METHODS: A retrospective case-control study of blood group O mothers and their ABO and Rh newborns was conducted. Medical records that included total serum bilirubin levels of 79 patients with hemolytic disease of the newborn (HDN) from between 2017 and 2020 were reviewed. Neonates who were eligible to receive immunoglobulin based on the American Academy of Pediatrics (AAP) guidelines were classified as cases and the rest were included as the Control Group. RESULTS: The mean total bilirubin in relation to hemoglobin levels in IVIG-treated neonates was significantly lower than in non-IVIG-treated neonates (13.98 ± 4.23 mg/dL versus 16.61 ± 2.68 mg/dL; p-value = 0.002). Although females had longer hospitalizations in both IVIG-treated (3.81 ± 1.28 versus 3.54 ± 1.30 days; p-value = 0.509) and non-IVIG-treated (3.43 ± 0.811 versus 3.19 ± 0.75 days; p-value = 0.361) groups compared to males, this difference was not significant between the groups. Although four neonates with ABO incompatibility required packed red blood cells, all infants were managed medically and no deaths occurred during the course of treatment. Moreover, no exchange transfusion or adverse effects of IVIG were observed. CONCLUSION: The results from the present study revealed that IVIG administration is a useful procedure for the management of bilirubin encephalopathy with greater opportunity to reduce exchange transfusion requirements for neonatal hyperbilirubinemia.

In vitro evaluation of human intravenous immunoglobulin in combination with antimicrobials and human serum against multidrug-resistant isolates of Acinetobacter baumannii.

The high incidence of multidrug-resistant (MDR) Acinetobacter baumannii has been a challenge for health worldwide, due to the reduction of therapeutic options, making the use of antimicrobial combinations necessary for the treatment, such as meropenem, amikacin, and colistin. Antibodies against bacterial species, mainly immunoglobulins G (IgG), are produced for acting as effector mechanisms (neutralization, opsonization, phagocytosis, and complement system activation). Some studies have demonstrated promising results of IgG in combination with antimicrobial preparations against bacterial infections, in which the direct action of IgG has restored the immune system balance. Serious problem caused by the increase of MDR A. baumannii isolates results in a constant search for therapeutic alternatives to defeat these infections. However, this study aims to verify in vitro the phagocytosis rate of the A. baumannii-infected human monocytes, as well as to analyze possible morphological changes induced by intravenous immunoglobulin G (IVIG) with human serum in association with antimicrobials. The phagocytosis rate and bacterial cell binding capacity of IVIG were determined for two A. baumannii isolates submitted to 4 mg/mL of human IVIG alone and in combination with different sub-minimum inhibitory concentrations (sub-MICs) of meropenem, amikacin, and colistin and processed for indirect immunofluorescence. Subsequently, these isolates were resubmitted and coupled with human serum and processed for scanning electron microscopy. There was no statistical difference for phagocytosis rates in the isolates tested. Bacterial isolates showed alterations in cell morphology when exposed to IVIG/human serum alone and in combination with antimicrobials such as alteration in shape, wrinkling, membrane depression, and especially cell rupture with extravasation of cytoplasmic material. The isolates visually differed in the IVIG binding to the bacterial cell, with higher fluorescence intensity, which corresponds to the highest IVIG binding, in the isolate more sensitive to meropenem, amikacin, and colistin. No differences between treatments were observed in the IVIG binding to the bacterial cell. The combined action of IVIG with meropenem, amikacin, and colistin against A. baumannii MDR isolates induced several bacterial cell damages. And when associated with human serum, a massive destruction of cells can be observed. These results may suggest the analysis of the use of IgG preparations for the treatment of A. baumannii MDR infections.

Therapeutic Window of Intravenous Immunoglobulin (IVIG) and its correlation with IVIG-resistant in Kawasaki Disease: a retrospective study

Abstract Objective: To investigate the optimal timing of initial intravenous immunoglobulin (IVIG) treatment in Kawasaki disease (KD) patients. Methods: KD patients were classified as the early group (day 1-4), conventional group (day 5-7), conventional group (day 8-10), and late group (after day 10). Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analyses and receiver operating characteristic (ROC) curve analysis. Results: There were no significant differences in IVIG resistance among the 4 groups (p = 0.335). The sensitivity analysis also confirmed no difference in the IVIG resistance between those who started the initial IVIG ≤ day 7 of illness and those who received IVIG >day 7 of illness (p = 0.761). In addition, patients who received IVIG administration more than 7 days from the onset had a higher proportion of coronary artery abnormalities (p = 0.034) and longer length of hospitalization (p = 0.033) than those who started IVIG administration less than 7 days. The optimal cut-off value of initial IVIG administration time for predicting IVIG resistance was >7 days, with a sensitivity of 75.25% and specificity of 82.41%. Conclusions: IVIG therapy within 7 days of illness is found to be more effective for reducing the risk of coronary artery abnormalities than those who received IVIG >day 7 of illness. IVIG treatment within the 7 days of illness seems to be the optimal therapeutic window of IVIG. However, further prospective studies with long-term follow-up are required.

Clinical Course Associated with Aseptic Meningitis Induced by Intravenous Immunoglobulin for the Treatment of Multisystem Inflammatory Syndrome in Children.

Aseptic meningitis is a rare but potentially serious complication of intravenous immunoglobulin treatment. In this case series, meningitic symptoms following intravenous immunoglobulin initiation in patients with multisystem inflammatory syndrome were rare (7/2,086 [0.3%]). However, they required the need for additional therapy and/or readmission.

Therapeutic Window of Intravenous Immunoglobulin (IVIG) and its correlation with IVIG-resistant in Kawasaki Disease: a retrospective study.

OBJECTIVE: To investigate the optimal timing of initial intravenous immunoglobulin (IVIG) treatment in Kawasaki disease (KD) patients. METHODS: KD patients were classified as the early group (day 1-4), conventional group (day 5-7), conventional group (day 8-10), and late group (after day 10). Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analyses and receiver operating characteristic (ROC) curve analysis. RESULTS: There were no significant differences in IVIG resistance among the 4 groups (p = 0.335). The sensitivity analysis also confirmed no difference in the IVIG resistance between those who started the initial IVIG ≤ day 7 of illness and those who received IVIG >day 7 of illness (p = 0.761). In addition, patients who received IVIG administration more than 7 days from the onset had a higher proportion of coronary artery abnormalities (p = 0.034) and longer length of hospitalization (p = 0.033) than those who started IVIG administration less than 7 days. The optimal cut-off value of initial IVIG administration time for predicting IVIG resistance was >7 days, with a sensitivity of 75.25% and specificity of 82.41%. CONCLUSIONS: IVIG therapy within 7 days of illness is found to be more effective for reducing the risk of coronary artery abnormalities than those who received IVIG >day 7 of illness. IVIG treatment within the 7 days of illness seems to be the optimal therapeutic window of IVIG. However, further prospective studies with long-term follow-up are required.

Severe coronavirus HCoV-NL63 pneumonia in a patient receiving blinatumomab with secondary antibody deficiency in COVID-19 times.

Introduction: Human coronavirus NL63 (HCoV-NL63) is one of four common human respiratory coronaviruses. It causes lower respiratory tract infections in young children, elderly and immunosuppressed people, which could result in fatal outcomes. In this time of pandemic, we want to highlight the importance of other coronaviruses infection besides SARS-CoV-2, especially in a patient with underlying conditions like acute lymphoblastic leukemia, receiving immunosuppressive therapy that could result in humoral secondary immunodeficiencies. Case report: We present the case of a 44-year-old Colombian man with acute lymphoblastic leukemia who developed HCoV-NL63 pulmonary infection after the first month of treatment with blinatumomab complicated with severe secondary hypogammaglobulinemia. HCoV-NL63 was detected by multiplex PCR, and HCoV-NL63 viral pneumonia was diagnosed. Hypogammaglobulinemia was studied by determining serum immunoglobulins levels and protein electrophoresis. The treatment consisted of supportive therapy and replacement with intravenous immunoglobulins. After therapy, the patient improved his oxygenation, and the infection was resolved in a few days. Conclusions: This case highlights the relevance of other coronaviruses infections besides SARS-CoV-2 in patients receiving immunosuppressive therapy who develop secondary antibody deficiency, and the importance of replacement therapy with intravenous immunoglobulins at early stage of infection with HCoV-NL63.

Guillain-Barré Syndrome in Mexico: An Updated Review Amid the Coronavirus Disease 2019 Era

ABSTRACT Guillain-Barré syndrome (GBS) is the most frequent cause of acute flaccid paralysis and if not diagnosed and treated timely, a significant cause of long-term disability. Incidence in Latin America ranges from 0.71 to 7.63 cases/100,000 person-years. Historically, GBS has been linked to infections (mainly gastrointestinal by Campylobacter jejuni) and vaccines (including those against severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]); however, a trigger cannot be detected in most cases. Regarding SARS-CoV-2, epidemiological studies have found no association with its development. Acute motor axonal neuropathy is the most common electrophysiological variant in Mexico and Asian countries. Intravenous immunoglobulin or plasma exchanges are still the treatment cornerstones. Mortality in Mexico can be as high as 12%. Advances in understanding the drivers of nerve injury in GBS that may provide the basis for developing targeted therapies have been made during the past decade; despite them, accurate criteria for selecting patients requiring acute treatment, prognostic biomarkers, and novel therapies are still needed. The newly-developed vaccines against SARS-CoV-2 have raised concerns regarding the potential risk for developing GBS. In the midst of coronavirus disease 2019 and vaccination campaigns against SARS-CoV-2, this review discusses the epidemiology, clinical presentation, management, and outcomes of GBS in Mexico.

Use of Intravenous Immunoglobulins and Systemic Corticosteroids in Patients with Toxic Epidermal Necrolysis: Experience of a Hospital in Mexico City. / Tratamiento con inmunoglobulina intravenosa y esteroides sistémicos en pacientes con necrólisis epidérmica tóxica: Experiencia en un hospital en Ciudad de México.

Toxic epidermal necrolysis is the most serious mucocutaneous adverse drug reaction. Multidisciplinary treatment and withdrawal of the causative drug are key to reducing mortality. Few studies have analyzed the use of systemic corticosteroids and intravenous immunoglobulins (IVIG) in patients with toxic epidermal necrolysis in Latin America. We describe our experience with 6 cases treated at a dermatology referral hospital in Mexico City. None of the patients died or developed complications in the short or medium term. The most widely used regimen was a combination of IVIG 1 g/kg for 3 to 5 days and methylprednisolone 1 g for 3 to 5 days. Mean hospital stay was 14.8 days. The combined use of systemic corticosteroids and IVIG seems to be a safe treatment option for patients with toxic epidermal necrolysis.

Guillain-Barré Syndrome in Mexico: An Updated Review Amid the Coronavirus Disease 2019 ERA.

Guillain-Barré syndrome (GBS) is the most frequent cause of acute flaccid paralysis and if not diagnosed and treated timely, a significant cause of long-term disability. Incidence in Latin America ranges from 0.71 to 7.63 cases/100,000 person-years. Historically, GBS has been linked to infections (mainly gastrointestinal by Campylobacter jejuni) and vaccines (including those against severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]); however, a trigger cannot be detected in most cases. Regarding SARS-CoV-2, epidemiological studies have found no association with its development. Acute motor axonal neuropathy is the most common electrophysiological variant in Mexico and Asian countries. Intravenous immunoglobulin or plasma exchanges are still the treatment cornerstones. Mortality in Mexico can be as high as 12%. Avances in understanding the drivers of nerve injury in GBS that may provide the basis for developing targeted therapies have been made during the past decade; despite them, accurate criteria for selecting patients requiring acute treatment, prognostic biomarkers, and novel therapies are still needed. The newly-developed vaccines against SARS-CoV-2 have raised concerns regarding the potential risk for developing GBS. In the midst of coronavirus disease 2019 and vaccination campaigns against SARS-CoV-2, this review discusses the epidemiology, clinical presentation, management, and outcomes of GBS in Mexico.

Utilización y farmacovigilancia de inmunoglobulina G endovenosa en un hospital pediátrico de alta complejidad / Intravenous immunoglobulin G use and pharmacovigilance in a tertiary care children's hospital

Introducción. La inmunoglobulina G endovenosa (IGEV) es un medicamento hemoderivado de inmunoglobulina G polivalente y policlonal. Posee un amplio espectro de indicaciones como inmunomodulador o como terapia de reemplazo. Asimismo, si bien se considera un tratamiento seguro, la incidencia de reacciones adversas reportadas en la literatura varía del 1 % al 81 %. Este trabajo tuvo como objetivo evaluar la utilización de IGEV y describir los acontecimientos adversos por la medicación en un hospital pediátrico de alta complejidad.Población y métodos. Se realizó un estudio de farmacoepidemiología, observacional y prospectivo. Se evaluaron pacientes que recibieron IGEV durante 7 meses, en 6 áreas de un hospital pediátrico de alta complejidad de la Ciudad Autónoma de Buenos Aires. La unidad de análisis fue cada infusión de IGEV, y la principal variable de estudio fue la presencia de reacciones adversas.Resultados. Se analizaron 305 infusiones en 111 pacientes. El 81,6 % de las indicaciones fueron de tipo supletorio. La dosis máxima utilizada fue 1 g/kg. En el 99,6 % de las infusiones, se indicó algún tipo de premedicación; la difenhidramina fue la droga más utilizada, aunque con diferentes posologías. Se registraron 12 reacciones adversas (el 3,9 % de las infusiones), tres de las cuales se consideraron graves: dos meningitis asépticas y una crisis comicial. Todas se resolvieron ad integrum.Conclusiones. La tasa de reacciones adversas de la IGEV en nuestro medio fue baja, con mayoría de reacciones leves e inmediatas y evolución favorable en todos los pacientes.

Introduction. Intravenous immunoglobulin G (IVIG) is a blood product from polyvalent and polyclonal immunoglobulin G. It covers a broad range of indications as immunomodulator or replacement therapy. In addition, although it is considered a safe therapy, the incidence of adverse reactions reported in the bibliography ranges from 1 % to 81 %. The objective of this study was to assess IVIG use and describe related adverse events in a tertiary care children's hospital.Population and methods. This was a pharmacoepidemiological, observational, and prospective study. Patients receiving IVIG for 7 months in 6 areas of a tertiary care children's hospital in the Autonomous City of Buenos Aires were assessed. The analysis unit was each IVIG infusion, and the main variable was the presence of adverse reactions.Results. A total of 305 infusions in 111 patients were analyzed. In 81.6 % of cases, the indication was for replacement. The maximum dose was 1 g/kg. In 99.6 % of infusions, some type of premedication was indicated; diphenhydramine was the most common drug, with varying dosages. A total of 12 adverse reactions (3.9 % of infusions) were recorded; 3 were severe: aseptic meningitis (2 cases) and seizures (1 case). All resolved to normal.Conclusions. The rate of IVIG adverse reactions in our setting was low; most reactions were mild and immediate and resolved favorably in all patients

Intravenous immunoglobulin G use and pharmacovigilance in a tertiary care children's hospital. / Utilización y farmacovigilancia de inmunoglobulina G endovenosa en un hospital pediátrico de alta complejidad.

INTRODUCTION: Intravenous immunoglobulin G (IVIG) is a blood product from polyvalent and polyclonal immunoglobulin G. It covers a broad range of indications as immunomodulator or replacement therapy. In addition, although it is considered a safe therapy, the incidence of adverse reactions reported in the bibliography ranges from 1 % to 81 %. The objective of this study was to assess IVIG use and describe related adverse events in a tertiary care children's hospital. POPULATION AND METHODS: This was a pharmacoepidemiological, observational, and prospective study. Patients receiving IVIG for 7 months in 6 areas of a tertiary care children's hospital in the Autonomous City of Buenos Aires were assessed. The analysis unit was each IVIG infusion, and the main variable was the presence of adverse reactions. RESULTS: A total of 305 infusions in 111 patients were analyzed. In 81.6 % of cases, the indication was for replacement. The maximum dose was 1 g/kg. In 99.6 % of infusions, some type of premedication was indicated; diphenhydramine was the most common drug, with varying dosages. A total of 12 adverse reactions (3.9 % of infusions) were recorded; 3 were severe: aseptic meningitis (2 cases) and seizures (1 case). All resolved to normal. CONCLUSIONS: The rate of IVIG adverse reactions in our setting was low; most reactions were mild and immediate and resolved favorably in all patients.

Introducción. La inmunoglobulina G endovenosa (IGEV) es un medicamento hemoderivado de inmunoglobulina G polivalente y policlonal. Posee un amplio espectro de indicaciones como inmunomodulador o como terapia de reemplazo. Asimismo, si bien se considera un tratamiento seguro, la incidencia de reacciones adversas reportadas en la literatura varía del 1 % al 81 %. Este trabajo tuvo como objetivo evaluar la utilización de IGEV y describir los acontecimientos adversos por la medicación en un hospital pediátrico de alta complejidad. Población y métodos. Se realizó un estudio de farmacoepidemiología, observacional y prospectivo. Se evaluaron pacientes que recibieron IGEV durante 7 meses, en 6 áreas de un hospital pediátrico de alta complejidad de la Ciudad Autónoma de Buenos Aires. La unidad de análisis fue cada infusión de IGEV, y la principal variable de estudio fue la presencia de reacciones adversas. Resultados. Se analizaron 305 infusiones en 111 pacientes. El 81,6 % de las indicaciones fueron de tipo supletorio. La dosis máxima utilizada fue 1 g/kg. En el 99,6 % de las infusiones, se indicó algún tipo de premedicación; la difenhidramina fue la droga más utilizada, aunque con diferentes posologías. Se registraron 12 reacciones adversas (el 3,9 % de las infusiones), tres de las cuales se consideraron graves: dos meningitis asépticas y una crisis comicial. Todas se resolvieron ad integrum. Conclusiones. La tasa de reacciones adversas de la IGEV en nuestro medio fue baja, con mayoría de reacciones leves e inmediatas y evolución favorable en todos los pacientes.

Treatment of discoid lupus erythematosus in a dog with human intravenous immunoglobulin

Background: Discoid lupus erythematosus (DLE) is a common canine autoimmune skin disease, in which systemic manifestations are absent. Skin Lesions are usually present on the nasal planum, and characterised by erythema, depigmentation, erosion, ulceration, and crusting. The diagnosis is based on histopathological results, which should demonstrate lymphoplasmacytic lichenoid-interface dermatitis. Human intravenous immunoglobulin (hIVIg) has been used in veterinary medicine to treat cutaneous diseases including erythema multiforme, PF, and severe adverse cutaneous drug reactions. In human medicine, it has been effective to treat DLE. This report firstly describes the clinical response to hIVIg in a dog with DLE resistant to common immunosuppressive drugs. Case: A 5-year-old, intact female Shih Tzu presented with a 1-month history of slowly progressive black crusting on the nasal planum, chin, and claw. Based on the results of a dermatologic examination, superficial pyoderma was diagnosed. The skin lesions did not improve during and after anti-infective treatment. After removing the crusts, a skin biopsy was obtained from the muzzle. Histopathology of lesional skin biopsy specimens revealed lymphoplasmacytic interface dermatitis at the dermoepidermal junction. Microscopic examination also revealed vacuolar changes and pigmentary incontinence of the basal layer as a lichenoid tissue reaction. No mites or fungi were detected on the skin section. The absence of acantholytic cells excluded pemphigus foliaceus, which is also characterised by the lesions of the nasal planum. Based on the distribution of the lesions, histopathology and exclusion of other dermatoses, the dog was diagnosed with DLE. The skin lesions temporarily improved after treatment with prednisolone (2 mg/kg PO q12h). However, after tapering the dose of prednisolone, new black crusts developed on the nasal planum and claw. Although the dog was successively treated with other immunosuppressive drugs, including azathioprine, cyclosporin with dexamethasone, and mycophenolate mofetil, black crusts still remained. Due to the low efficacy of these immunosuppressive drugs, hIVIg was administered at 0.5 g/kg once daily for 4 days, for a total dose of 2 g/kg. During hIVIg administration, the crusted lesions gradually improved. After the hIVIg administration, the dog was treated with prednisolone (1 mg/kg PO q12h). The lesions were almost in complete remission at 21 days after an additional application of prednisolone. The skin lesions did not recur, and the treatment was eventually discontinued after 6 weeks of additional prednisolone application. Discussion: The standard treatment of canine DLE includes glucocorticoids, and second-line immunosuppressive drugs, such as azathioprine and cyclosporine, are usually added in cases resistant to steroids. This case suggests that hIVIg may be beneficial as an adjunctive treatment option for canine DLE, especially when the application of standard immunosuppressive drugs is limited due to adverse effects or low efficacy. There is evidence from several studies that the steroid-sparing effect of hIVIg is significant in human patients. In the current case, the effective dose of prednisolone was reduced to 2 mg/kg/day after hIVIg administration, and prednisolone therapy was finally discontinued completely. The hIVIg appears to lower the daily steroid dose requirement in this dog.

[Giant coronary aneurysms in infant with Kawasaki disease shock syndrome]. / Aneurismas coronarios gigantes en lactante con síndrome de choque por enfermedad de Kawasaki.

BACKGROUND: Kawasaki disease shock syndrome is a rare presentation of Kawasaki disease, in which cardiovascular manifestations associated with elevated inflammation biomarkers that develop hypotension are observed. It is preceded by gastrointestinal and neurological manifestations, with an increased risk of coronary lesions and resistance to intravenous immunoglobulin. CASE REPORT: A 5-month-old male patient with a fever that had developed in the last week, gastrointestinal and neurological symptoms with hypotensive shock, urticarial rash, BCG lymphadenitis, and edema of palms and soles. Giant coronary aneurysms were evident, so Kawasaki disease shock syndrome was diagnosed, which was treated with corticosteroid pulse and intravenous immunoglobulin. CONCLUSIONS: Clinicians must suspect Kawasaki disease shock syndrome when there is hypotensive shock, and the gastrointestinal, neurological and mucocutaneous symptoms that are characteristic of the disease, especially in infants under one year of age. The timely treatment of this disease reduces severe complications.

Antecedentes: El síndrome de choque es una presentación poco habitual de la enfermedad de Kawasaki en el que se observan manifestaciones cardiovasculares asociadas con niveles elevados de marcadores de inflamación, que llevan a hipotensión. Es precedido por manifestaciones gastrointestinales y neurológicas y existe mayor riesgo de lesiones coronarias y resistencia a inmunoglobulina intravenosa. Caso clínico: Varón de cinco meses de edad con fiebre de una semana de evolución, síntomas gastrointestinales y neurológicos con choque hipotensivo, erupciones urticariforme, linfadenitis por vacunación con bacilo de Calmette-Guérin, así como edema de manos y pies. Se evidenciaron aneurismas coronarios gigantes, por lo que se diagnosticó síndrome de choque por enfermedad de Kawasaki, el cual fue tratado con pulso de corticoesteroide e inmunoglobulina intravenosa. Conclusiones: El diagnóstico de síndrome de choque por enfermedad de Kawasaki se debe sospechar por choque hipotensivo, síntomas gastrointestinales, neurológicos y mucocutáneos propios de la enfermedad, especialmente en menores de un año. El tratamiento oportuno reduce las complicaciones graves.

Delayed Development of Coronary Artery Aneurysm in Patients with Kawasaki Disease Who Were Clinically Responsive to Immunoglobulin.

OBJECTIVE: To clarify the frequency and characteristics of discrepant outcomes of intravenous immunoglobulin (IVIG) between fever and coronary artery aneurysms (CAAs) in patients with Kawasaki disease. STUDY DESIGN: This study included 325 patients who responded to oral aspirin and IVIG alone. The main outcome was CAA 4 weeks after disease onset. CAA was defined as ≥2.5 of maximum z score (Zmax) representing the highest value of 4 coronary artery branches. Immunoglobulin dosage and sequential changes in Zmax were reviewed to investigate the effects on fever and timing of CAA development. Logistic regression analyses with receiver operating characteristic curves using clinical and laboratory variables including the initial Zmax were performed to identify predictors of CAA at 4 weeks. RESULTS: CAAs were either persistent or appeared de novo 4 weeks after diagnosis in 13 of 325 patients who responded to a single or repeated IVIG. Four single-dose IVIG-responders developed CAA although they had pretreatment Zmax of <2.0. The 2 single-dose IVIG responders with the greatest pretreatment Zmax (>4.5) developed persistent CAA. Receiver operating characteristic analysis demonstrated Zmax of 2.57 as the cut-off for predicting CAA. Multivariable analyses identified >2.5 Zmax (OR 9.08, 95% CI 1.26-65.3, P = .028, 50% sensitivity, 91% specificity) as the sole risk factor for CAA at 4 weeks in single-dose IVIG responders. CONCLUSIONS: Delayed development and persistence of CAA in single-dose IVIG responders indicate that some factors other than those responsible for systemic inflammation may contribute to vasculitis in CAA. Baseline Zmax 2.5 aids in predicting CAAs.

[Chronic kidney disease in adults with primary immunodeficiency diseases in treatment with intravenous immunoglobulin]. / Enfermedad renal crónica en adultos con inmunodeficiencias primarias en tratamiento con inmunoglobulina intravenosa.

BACKGROUND: Intravenous immunoglobulin (IVIG) is the treatment of choice for humoral primary immunodeficiency diseases (PIDs). A third of the patients who receive intravenous immunoglobulin have adverse reactions, such as osmotic nephrosis. OBJECTIVE: To assess the presence of kidney disease in adults with humoral PIDs, in treatment with intravenous immunoglobulin. METHODS: A cross-sectional, descriptive, and observational study of patients who belong to the PID Clinic of the Specialties Hospital of the National Medical Center "Siglo XXI", Mexico City, who receive treatment with intravenous immunoglobulin. A questionnaire with demographic information, 24h urine creatinine clearance, serum creatinine, urea, and BUN (Blood Urea Nitrogen) was applied. RESULTS: 35 patients were surveyed; 65.7 % were women; the average age was 34 years; 51.4 % of the patients presented kidney damage. Those with > 5 years of treatment with intravenous immunoglobulin presented chronic kidney disease (CKD) with more frequency (55.6 %) according to the KDOQI scale. CONCLUSIONS: Chronic kidney disease occurs in 51 % of adult patients with PID who have been treated with intravenous immunoglobulin for more than 5 years; which is why these patients require periodic evaluations of their kidney function, and the use of sugar-free immunoglobulin in order to reduce the risk.

Antecedentes: La inmunoglobulina intravenosa es el tratamiento de elección para inmunodeficiencias primarias (IDP) humorales. Un tercio de los pacientes que reciben inmunoglobulina intravenosa presenta reacciones adversas, como nefrosis osmótica. Objetivo: Evaluar la presencia de enfermedad renal en adultos con IDP humorales y en tratamiento con inmunoglobulina intravenosa. Métodos: Estudio transversal, descriptivo y observacional de pacientes pertenecientes a la Clínica de Inmunodeficiencias Primarias del Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Ciudad de México, que reciben tratamiento con inmunoglobulina intravenosa. Se les aplicó un cuestionario con datos demográficos, depuración de creatinina en orina de 24 horas, creatinina sérica, urea y análisis de nitrógeno ureico en sangre. Resultados: Se encuestó a 35 pacientes, 65.7 % fue del sexo femenino; la edad promedio fue de 34 años; 51.4 % presentó daño renal, con mayor frecuencia enfermedad renal crónica (55.6 %) cuando tenían más de cinco años de tratamiento con inmunoglobulina intravenosa, de acuerdo con la escala de la Kidney Disease Outcomes Quality Initiative. Conclusiones: La enfermedad renal crónica se presenta en 51 % de los pacientes adultos con IDP en tratamiento con inmunoglobulina intravenosa por más de cinco años, por lo que esta población requiere evaluación periódica de la función renal y utilización de inmunoglobulina sin azúcares para reducir el riesgo.

[Clinical characteristics of primary immunodeficiencies in children from a tertiary hospital]. / Características clínicas de las inmunodeficiencias primarias en niños de un hospital de tercer nivel.

BACKGROUND: Primary immunodeficiencies are diseases that are caused by one or more defects in the immune system. OBJECTIVE: The purpose of the article is to describe the characteristics of the immunodeficiencies that were diagnosed in a pediatric hospital, which forms a reference center in the West of Mexico. METHODS: A cross-sectional study of pediatric patients with primary immunodeficiency in a pediatric hospital in Guadalajara, Jalisco. RESULTS: 60 patients were registered, of which 21% were female, and 78% were male. Predominant immunodeficiencies of antibodies formed the largest group (46% of patients). X-linked agammaglobulinemia was the most frequent immunodeficiency (21%); other frequent diagnoses were common variable immunodeficiency, and IgG subclass deficiency. The average age of the patients that were diagnosed was of 6.3 years. The most common initial manifestations were infectious processes (46%), and pneumonia was the frequent diagnosis (30%). Autoimmune manifestations were observed in 13% of patients; 67% of the patients were found with immunoglobulin replacement therapy, with which a decrease in hospitalizations from 3.2 times to 0.13 times was observed. There were two deceased patients due to surgical complications of cardiac correction and intestinal reconnection. CONCLUSION: Knowing the behavior of primary immune deficiencies in our environment allows the opening of areas of opportunity in order to improve the survival and quality of life of our patients.

Antecedentes: Las inmunodeficiencias primarias son un grupo de enfermedades causadas por uno más defectos del sistema inmunitario. Objetivo: Describir las características de las inmunodeficiencias diagnosticadas en un hospital pediátrico de tercer nivel, que constituye un centro de referencia en el Occidente de México. Métodos: Estudio transversal de pacientes pediátricos con inmunodeficiencias primarias atendidos en un hospital pediátrico en Guadalajara, Jalisco. Resultados: Se registraron 60 pacientes, 21 % mujeres y 78 % hombres. Las inmunodeficiencias predominantes de anticuerpos constituyeron el grupo más numeroso (46 %). La agammaglobulinemia ligada al cromosoma X fue la inmunodeficiencia más frecuente, con 21 % del registro. Otros diagnósticos frecuentes fueron inmunodeficiencia común variable y deficiencia de subclases de IgG. El promedio de edad al diagnóstico fue de 6.3 años. Las manifestación inicial más común fueron los procesos infecciosos (46 %) y la neumonía fue el diagnóstico más frecuente (30 %). Las manifestaciones autoinmunes se observaron en 13 % de los pacientes; 67 % de los pacientes se encontró con sustitución de inmunoglobulina, con la cual se observó disminución en las hospitalizaciones: de 3.2 a 0.13 veces. Fallecieron dos pacientes por complicaciones quirúrgicas de corrección cardiaca y reconexión intestinal. Conclusión: El conocimiento del comportamiento de las inmunodeficiencias primarias en nuestro medio permite apertura de áreas de oportunidad a fin de mejorar la supervivencia y calidad de vida de los pacientes.

Profilaxis combinada con inmunoglobulina intravenosa y plasmaféresis en pacientes altamente sensibilizados, receptores de trasplante renal o combinado hígado-riñón: experiencia en un centro médico colombiano / Combined prophylaxis with intravenous immunoglobulin and plasmapheresis in highly sensitized patients, recipients of kidney or combined liver-kidney transplant: experience in a Colombian medical center

El trasplante renal constituye la mejor opción de tratamiento para los pacientes con enfermedad renal crónica terminal. La supervivencia del injerto es de gran importancia y puede ser afectada por factores inmunológicos o no inmunológicos; esto unido al número de pacientes en las listas de espera, hace necesario definir estrategias de manejo que permitan tener mejores resultados a largo plazo. Objetivo. Determinar las características clínicas y humorales, y los desenlaces en receptores de trasplante renal o combinado hígado-riñón, altamente sensibilizados, que recibieron profilaxis combinada con inmunoglobulina intravenosa y plasmaféresis en el Hospital San Vicente Fundación, en Colombia. Materiales y métodos. Se realizó un estudio retrospectivo, observacional, descriptivo, que incluyó los pacientes trasplantados entre el 4 de julio de 2010 y el 19 de abril de 2017. Como variables se incluyeron, entre otras, la etiología de la enfermedad renal crónica, el tipo de terapia recibida, y el tiempo en lista de espera en días. Como desenlace se evaluó la presencia de rechazo, el tipo de rechazo, la pérdida del injerto, las complicaciones y la muerte. Resultados. Del total de 25 pacientes, el 100% recibió inmunoglobulina intravenosa y el 84% plasmaféresis. El 12% presentó rechazo del injerto, todos de tipo humoral, y el 20% perdió el injerto. Discusión. A pesar de la gran variedad de protocolos propuestos en la literatura, en esta población especial no se ha establecido un protocolo óptimo de inmunosupresión. El protocolo en nuestra pequeña cohorte no tuvo un impacto negativo en el porcentaje de infecciones postrasplante ni en la pérdida del injerto renal, pero sí redujo el tiempo en las listas de espera; por lo tanto, se requieren estudios adicionales para confirmar los hallazgos encontrados en este estudio

Kidney transplantation is the best treatment option for patients with terminal chronic kidney disease, regardless of the etiology, making graft survival an important feature, which may be affected by immunological or non-immunological factors. This, added to the increasing number of patients on waiting lists, makes it necessary to define management strategies for these patients that allow better long-term results. Objectives. To determine the clinical, humoral and outcome characteristics in highly sensitized recipients of kidney and simultaneous kidneyliver transplant who received combined prophylaxis with intravenous immunoglobulin and plasmapheresis therapy in a Colombian medical center. Materials and methods. A retrospective, observational, descriptive study was carried out that included the transplanted patients between July 4, 2010 and April 19, 2017. Variables included the etiology of chronic kidney disease, the type of therapy received, and waiting time in days, among others. As outcomes, the presence of rejection, type of rejection, graft loss, complications and death were evaluated. Results. From a total of 25 patients, 100% received intravenous immunoglobulin and 84% plasmapheresis. Twelve percent presented graft rejection, all humoral, and 20% lost the graft. Discussion. Despite the great variety of protocols proposed in the literature, an optimal immunosuppression protocol has not been established for this particular population. The protocol in our small cohort did not have a negative impact on the percentage of post-transplant infections nor in the loss of the renal graft, but it did reduce waiting time; therefore, additional studies are required to confirm the findings in this study

TREATMENT STRATEGIES AND OUTCOME OF PARVOVIRUS B19 INFECTION IN KIDNEY TRANSPLANT RECIPIENTS: A CASE SERIES AND LITERATURE REVIEW OF 128 PATIENTS.

BACKGROUND: There is no specific antiviral treatment for parvovirus B19 (PVB19) infection. OBJECTIVE: The objective of this study was to study the treatment and outcome of PVB19 infection in kidney transplant recipients (KTR) at our institution, and cases published in the medical literature. METHODS: We conducted a retrospective review of PVB19 infection in KTR at an academic medical center over a 16-year period and summarized the data on its treatment and outcome in 120 KTR in the medical literature. RESULTS: In our cohort of eight patients, the median time to the onset of PVB19 disease was 7.2 weeks after transplantation. All patients had severe aregenerative anemia (mean hemoglobin (Hb) of 6.2 ± 1.0 g/dl); all were treated with a reduction in their immunosuppressive regimen and the administration of single-dose intravenous immunoglobulin (IVIG) (mean total dosage of 0.87 ± 0.38 g/kg). The median time to anemia improvement (Hb >10 g/dl) was 3-week post-treatment. No recurrences were documented during follow-up (median 25 months). Among 128 patients (including our cohort of 8 and 120 reported in literature), therapeutic strategies included: 43% IVIG alone, 39% IVIG and reduced immunosuppression, 9% reduction of immunosuppression, and 9% conservative therapy. Clinical relapses were observed in 35% of 71 reported cases. CONCLUSIONS: In KTR, decreasing immunosuppression and the administration of low-dose immunoglobulin seem to be not worse than the standard dose in PVB19 infection.