Características de algunos parámetros de la inmunidad humoral y celular en pacientes con linfedema / Characteristics of some humoral and cellular immunity´s parameters in patients with lymphedema

Introducción: El linfedema es una enfermedad crónica con un impacto negativo sobre la salud de las personas que lo padecen. Este se considera un problema de salud subestimado y subregistrado, por lo que requiere de mayores esfuerzos investigativos y sanitarios. Objetivo: Identificar las características de algunos parámetros de la inmunidad humoral y celular en pacientes con linfedema del municipio El Cerro. Métodos: Se realizó un estudio descriptivo en 48 pacientes residentes en el municipio Cerro, atendidos en consulta externa del Instituto Nacional de Angiología y Cirugía Vascular en el período 2011-2015. El grupo se dividió en 24 pacientes con linfedema y 24 sin la enfermedad. A todos se les cuantificaron las concentraciones de las inmunoglobulinas (A, G y M) y de la proteína C reactiva. También se les hizo la prueba de hipersensibilidad retardada. Se utilizó chi cuadrado no paramétrico para asociar el estado inmunológico con la presencia de linfedema, la etiología y los estadios de este. Se trabajó con una confiabilidad del 95 por ciento (p < 0,05). Resultados: Predominaron los pacientes del sexo femenino (58,3 por ciento) y los de 60 años y más (29,2 por ciento). Hubo mayor frecuencia de linfangitis recurrentes (70,8 por ciento), con predominio del linfedema secundario en estadio IIb (45,8 por ciento); de afectación del miembro inferior derecho (45,8 por ciento), con una diferencia significativa de las inmunoglobulinas (IgA e IgG); y de frecuencia de pacientes anérgicos (91,7 por ciento), con proteína C reactiva positiva (45,8 por ciento). Conclusiones: Los pacientes con linfedema tienen afectados su sistema inmune, con mayor frecuencia de anérgicos, diminución de las inmunoglobulinas IgA e IgG, y positividad de proteína C reactiva(AU)

Introduction: Lymphedema is a chronic disease with a negative impact on the health of patients with lymphedema. It is considered an underestimated and sub-recorded health problem, which requires greater research and health efforts. Objective: Identify the characteristics of some parameters of humoral and cellular immunity in patients with lymphedema from Cerro municipality. Methods: A descriptive study was carried out in 48 patients living in Cerro municipality, who were attended in the external consultation of the National Institute of Angiology and Vascular Surgery in the period 2011-2015. The group was divided into 24 patients with lymphedema and 24 patients without the disease. The concentrations of immunoglobulins (A, G and M) and C-reactive protein were quantified in all of them. The test of delayed hypersensitivity was also perfomed. Non-parametric chi-square was used to associate immune state with the presence of lymphedema, etiology and lymphedema stages. Reliability was of 95 percent (p<0.05). Results: Female patients predominated (58.3 percent) and those of 60 years and older (29.2 percent). There was a higher frequency of recurrent lymphangitis (70.8 percent), predominantly stage II b secondary lymphedema (45.8 percent); lower right limb involvement (45.8 percent), with a significant difference of immunoglobulins (IgA and IgG); and frequency of anergic patients (91.7 percent), with positive C-reactive protein (45.8 percent). Conclusions: Patients with lymphedema have their immune system affected, more frequently the anergic ones, a decrease of IgA and IgG immunoglobulins, and positivity of C-reactive protein(AU)

Tubercúlide papulonecrótica: um relato de caso / Papulonecrotic tuberculids: a case report / Tubercúlide papulonecrótica: un informe de caso

As tubercúlides são reações de hipersensibilidade cutânea aos antígenos do Mycobacterium tuberculosis. Este é o caso de uma mulher de 45 anos que procurou a Unidade Básica de Saúde (UBS) com um quadro de eritema nodoso com mais de 10 anos de evolução, de etiologia desconhecida, e que evoluía como nódulos em pescoço e membros, que se tornavam úlceras necróticas, cicatrizavam e recidivavam periodicamente. Biópsias das lesões evidenciavam um processo inflamatório granulomatoso com extensa necrose, sugestivo de tuberculose, mas sem a presença do bacilo. Após anos sem tratamento adequado, finalmente levantou-se a hipótese de tubercúlide papulonecrótica. A paciente iniciou tratamento com o esquema básico (2RHZE/4RH) e dessensibilização vacinal, recebendo alta por cura.

Las tubercúlides son reacciones de hipersensibilidad cutánea a los antígenos del Mycobacterium tuberculosis. Este es el caso de una mujer de 45 años que buscó la Unidad Básica de Salud (UBS) con un cuadro de eritema nodoso con más de 10 años de evolución, de etiología desconocida, y que evolucionaba como nódulos en cuello y miembros, que se tornaban úlceras necróticas, cicatrizaban y recidivaban periódicamente. Las biopsias de las lesiones evidenciaban un proceso inflamatorio granulomatoso con una extensa necrosis, sugestiva de tuberculosis, pero sin la presencia del bacilo. Después de años sin tratamiento adecuado, finalmente se levantó la hipótesis de tubercúlide papulonecrótica. La paciente inició tratamiento con el esquema básico (2RHZE / 4RH) y desensibilización vacunal, recibiendo alta por curación

The tuberculids are cutaneous hypersensitivity reactions to Mycobacterium tuberculosis antigens. This is the case of a 45-year-old woman who sought the Basic Health Unit (BHU) with erythema nodosum with a 10-year evolution, of unknown etiology, that evolved as nodules in the neck and limbs, which became necrotic ulcers, cicatrized and recurred periodically. Biopsies of the lesions revealed a granulomatous inflammatory process with extensive necrosis, suggestive of tuberculosis, but without the presence of the bacillus. After years without adequate treatment, the hypothesis of papulonecrotic tuberculids finally arose. The patient started treatment with the basic regimen (2RHZE/4RH) and vaccine desensitization, receiving discharge by cure.

Delayed-Onset Anaphylaxis Caused by IgE Response to Influenza Vaccination

Influenza vaccine-associated anaphylaxis is a very rare allergic reaction to vaccines, but the most concerning and life-threatening adverse reaction. Although the safety of influenza vaccines has been well documented, occasional cases of anaphylaxis in vaccinated patients have been reported. In this study, we analyzed the immunoglobulin E (IgE) response to whole influenza vaccines in a pediatric case of delayed-onset anaphylaxis after influenza vaccination. The patient showed elevated specific IgE levels against whole influenza vaccines, especially with split virion from egg-based manufacturing process. Specific IgE levels to influenza vaccines showed decreased over. We evaluated a causal relationship between influenza vaccine and anaphylaxis event by enzyme-linked immunosorbent assay. Delayed-onset anaphylaxis after influenza vaccination can occur in children without predisposing allergic diseases. In addition, the results suggested that formulation and production system of influenza vaccines could affect the probability of severe allergic reaction to vaccines.

Hipersensibilidade a drogas: um alerta em pacientes portadores de doenças autoimunes / Drug hypersensitivity: an alert in patients with autoimmune diseases

Objetivo: Avaliar a hipersensibilidade a medicamentos em pacientes com o diagnóstico de doenças autoimunes. Métodos: Estudo clínico, analítico, do tipo caso-controle. Foram selecionadas 35 mulheres com doenças autoimunes e 35 sem esse diagnóstico que participaram do protocolo de pesquisa sobre antecedentes de hipersensibilidade a drogas. Resultados: As pacientes apresentavam idade variando de 16 a 66 anos, com a mediana semelhante nos dois grupos. A doença autoimune mais prevalente foi o lupus eritematoso sistêmico, 24/35 (68,5%). A proporção de hipersensibilidade a medicamentos, nas pacientes com doenças autoimunes, foi de 14/35 (40%), e apenas 2/35 (5,7%) no grupo controle (p = 0,0029). As reações de hipersensibilidade do tipo tardia foram as mais frequentes, e na maioria dos casos precederam o diagnóstico de doença autoimune em um total de cinco pacientes, sendo que destas cinco, duas apresentaram síndrome de Stevens Johnson, duas exantema maculopapular, e uma eritema fixo pigmentar. O grupo de drogas mais envolvido foi os anti-inflamatórios não esteroides, seguidos pelos anticonvulsivantes. Conclusão: Hipersensibilidade a medicamentos foi mais frequente em pacientes portadoras de doenças autoimunes, e pode preceder o diagnóstico, especialmente se for do tipo tardia. Estudos adicionais multicêntricos para verificar uma eventual associação de hipersensibilidade a medicamentos e doenças autoimunes são necessários.

Objective: To evaluate drug hypersensitivity in patients with autoimmune diseases. Methods: In this clinical, analytical, casecontrol study, we selected 35 women with autoimmune diseases and 35 women without this diagnosis to participate in this research protocol on history of drug hypersensitivity. Results: Patients' age ranged from 16 to 66 years with similar median in both groups. The most prevalent autoimmune disease was systemic lupus erythematosus, in 24/35 (68.5%) patients. The proportion of drug hypersensitivity was 14/35 (40%) in the autoimmune disease group and only 2/35 (5.7%) in the control group (p = 0.0029). Delayed hypersensitivity reactions were most frequent and preceded the diagnosis of autoimmune disease in five patients, including two with Stevens-Johnson syndrome, two with maculopapular rash and one with fixed pigmented erythema. The most frequently involved group of drugs was nonsteroidal anti-inflammatory drugs, followed by anticonvulsants. Conclusion: Drug hypersensitivity was more common in patients with autoimmune diseases and may precede the diagnosis, especially in delayed-type. Additional multicenter studies are required to evaluate a possible association of drug hypersensitivity to autoimmune diseases.

A case of rapid desensitization for rituximab-induced delayed hypersensitivity reaction

Rituximab is a monoclonal antibody used for the treatment of B-cell malignancies, including diffuse large B-cell lymphoma. Infusion-related hypersensitivity reactions to rituximab is well known, and delayed hypersensitivity reactions to rituximab are also reported. Desensitization is commonly used to prevent immediate hypersensitivity reactions, but recently there have been cases of successful desensitization therapy for delayed hypersensitivity reactions. A 66-year-old patient who underwent rituximab treatment for diffuse large B-cell lymphoma showed repeated rituximab-induced delayed hypersensitivity reactions with whole body rashes. Intravenous rapid desensitization was performed by using a 1-bottle, 11-step protocol for 6 cycles and thereafter hypersensitivity reaction did not recur. We herein reported a case of delayed hypersensitivity reaction caused by rituximab, which was successfully desensitized using our 11-step protocol.

Successful cholecalciferol desensitisation in a case of delayed hypersensitivity

Hypersensitivity to cholecalciferol (vitamin D3) or its active metabolite, calcitriol, is an exceedingly rare clinical phenomenon, with only 2 previously reported cases of suspected immediate hypersensitivity. Diagnosis of delayed drug hypersensitivity reactions is inherently difficult due to the lack of any robust in vitro diagnostic assay, particularly in those patients for whom provocation testing confers an unacceptable risk. In these situations, diagnosis relies on reproducible clinical manifestations following administration of the culprit agent, resolution upon its withdrawal and exclusion of other potential differential diagnoses. Based on these criteria, we propose the first reported case of delayed hypersensitivity to cholecalciferol successfully managed with a desensitisation protocol to pure cholecalciferol.

Vasculite urticariforme e exantema: uma reação de hipersensibilidade tardia mista a dimenidrinato ­ relato de caso / Urticarial vasculitis and rash: a mixed delayed hypersensitivity reaction to dimenhydrinate ­ case report

Dimenidrinato é um anti-histamínico H1 do grupo das etanolaminas, com importantes propriedades anticolinérgicas, antisserotoninérgicas e sedativas. Relatamos um caso de uma mulher que após 14 dias de ter usado dimenidrinato, iniciou quadro de exantema e vasculite urticariforme, além de sintomas constitucionais. Avaliação laboratorial sem alterações. Biopsia de pele evidenciou dermatite de interface do tipo vacuolar e púrpura com leucocitoclasia e derrame pigmentar. Imunofluorescência positiva para IgG, com presença de fluorescência dos núcleos dos queratinócitos da epiderme. Tratada com corticoide oral por 2 meses até remissão completa do quadro, e posterior realização de teste intradérmico, que foi positivo na leitura de 48h. A reação de hipersensibilidade tardia observada foi relacionada a mecanismo misto de Gell e Coombs (III e IV), com positividade no teste cutâneo intradérmico de leitura tardia em 48h (reação tipo IV) e biópsia compatível com vasculite cutânea (reação tipo III); lesões exantemáticas (reação tipo IV) e urticária vasculítica (reação tipo III). O teste cutâneo com dimenidrinato positivo reforça o diagnóstico de reação de hipersensibilidade.

Dimenhydrinate is an H1 antihistamine from the ethanolamine group, with important anticholinergic, antiserotoninergic and sedative properties. We report the case of a woman who, after 14 days of using dimenhydrinate, developed rash and urticarial vasculitis, in addition to constitutional symptoms. Laboratory tests were normal. Skin biopsy revealed interface purpuric dermatitis with leukocytoclasia and pigment effusion. Immunofluorescence was positive for IgG, showing nuclear fluorescence of epidermal keratinocytes. She was treated with oral corticosteroid for 2 months until complete remission of symptoms. Subsequent intradermal test resulted positive on the 48-h reading. The delayed hypersensitivity reaction was related to a mixed Gell and Coombs mechanism (III and IV), with positive results in the intradermal cutaneous test on the 48-h reading (type IV reaction) and a biopsy compatible with cutaneous vasculitis (type III reaction), exanthematous lesions (type IV reaction,) and urticarial vasculitis (type III reaction). The positive skin test for dimenhydrinate reinforces the diagnosis of hypersensitivity reaction.

The Incidence of Delayed-Type Hypersensitivity Reactions to Apples Among Patients Allergic to Birch Pollen

The major apple allergen Mal d 1 cross-reacts with the homologous birch pollen allergen Bet v 1 and causes immunoglobulin E (IgE)-mediated immediate-type allergic reactions. In some patients, delayed-type hypersensitivity to apples may develop within 72 hours without evidence of specific IgE or a positive skin prick test (SPT). The aim of the study was to evaluate the concomitance of delayed-type hypersensitivity reactions and immediate IgE-mediated reactions against high- and low-allergenic apple cultivars in patients with birch pollen allergy. Data were obtained from 45 adults with clinical symptoms of birch pollen allergy. Patients were exposed to apple pulp via atopy patch tests (APTs) and SPTs. Levels of IgE specific to Bet v 1 and Mal d 1 were measured with a radioallergosorbent test. Patients allergic to birch pollen showed the highest rate of positive SPT responses to Golden Delicious apples and the lowest rate to low-allergenic cultivar Grey French Reinette. Among these patients, 9% developed delayed hypersensitivity reactions to either Golden Delicious or Grey French Reinette apples; these reactions manifested clinically as erythema with papules (class ++). Fifty percent of APT-positive patients were concomitantly SPT-negative. Here, we show for the first time the clinical relevance of T cell-driven allergic reactions to apples. APTs may reveal type IV sensitization in patients who are negative for the corresponding type I sensitization tests. Thus, utilization of the APT procedure with fresh apple appears to be a valuable tool for the diagnosis of apple allergy and may improve the accuracy of food allergy diagnoses.

Pyrazinamide-Induced Urticaria and Angioedema: a Case Report / 대한내과학회지

Pyrazinamide (PZA) is an anti-tuberculosis drug and an essential component of the standard four-drug regimen for tuberculosis. Here, we report a case of immediate angioedema secondary to PZA administration intended for pulmonary tuberculosis treatment. A previously healthy 48-year-old woman was diagnosed with pulmonary tuberculosis and tuberculous lymphadenitis. Thirty minutes after taking the first dose of isoniazid, rifampicin, pyrazinamide, and ethambutol, the patient developed facial edema, generalized rash, and dizziness. An oral provocation test was performed on the four drugs, and 1,000 mg pyrazinamide showed a positive result characterized by 50 minutes of urticaria, angioedema, and hypotension. As the prevalence of tuberculosis increases, prescriptions for anti-tuberculosis drugs may increase as well. Clinicians should be aware of the possibility of immediate hypersensitivity as well as delayed hypersensitivity to anti-tuberculosis drugs.

Successful desensitization to fluconazole induced delayed hypersensitivity: A case report

Fluconazole is a triazole-based first-generation antifungal agent and has excellent effects on candidiasis and cryptococcosis. Hypersensitivity has been reported as a side effect of fluconazole. A 76-year-old female patient used fluconazole for consolidation therapy for cryptococcal meningitis, but showed delayed hypersensitivity with skin rashes and itching sensation of the whole body. For desensitization, was attempted by administering 12-step, 1:1 fluconazole solutions were administered intravenously at sequentially increasing infusion rates. After successful quick desensitization to fluconazole, fluconazole was continuously used as a consolidation therapy for cryptococcal meningitis. We herein report a case of delayed hypersensitivity reaction to fluconazole in consolidation therpy with cryptococcal meningitis who successfully completed desensitization.

Proper Cut-off Levels of Serum Specific IgE to Cefaclor for Patients with Cefaclor Allergy

PURPOSE: Cefaclor, a second-generation oral cephalosporin, is known to cause IgE-mediated hypersensitivity. Assays of serum-specific IgE (sIgE) to cefaclor are commercially available via the ImmunoCAP system (Thermo Fisher Scientific). While serum levels of sIgE >0.35 kU/L are considered indicative of an allergy, some patients with cefaclor allergy show low serum IgE levels. This study aimed to evaluate the proper cut-off levels of sIgE in the diagnosis of immediate hypersensitivity to cefaclor. MATERIALS AND METHODS: A total of 269 patients with drug allergy history, who underwent assays of sIgE to cefaclor at Ajou University hospital and Dong-A University Hospital, were reviewed retrospectively. Among them, 193 patients exhibited cefaclor-induced immediate hypersensitivity with certain or probable causality of an adverse drug reaction according to the WHO-UMC (the World Health Organization-the Uppsala Monitoring Centre) algorithm, and 76 controls showed delayed hypersensitivity reactions to non-antibiotics. RESULTS: In total, 126 of the 193 patients (65.3%) experienced anaphylaxis; they had higher serum sIgE levels than patients with immediate hypersensitivity who did not experience anaphylaxis (6.36±12.39 kU/L vs. 4.28±13.61 kU/L, p < 0.001). The best cut-off value for cefaclor-induced immediate hypersensitivity was 0.11 kU/L, with sensitivity of 80.2% and specificity of 81.6%. A cut-off value of 0.44 kU/L showed the best sensitivity (75.4%) and specificity (65.7%) for differentiating anaphylaxis from immediate hypersensitivity reactions. CONCLUSION: Patients with cefaclor anaphylaxis exhibit high serum IgE levels. A cut-off value of 0.11 kU/L of sIgE to cefaclor is proper for identifying patients with cefaclor allergy, and 0.44 kU/L may be useful to detect anaphylaxis.

Mycobacterium tuberculosis ESAT6 and CPF10 Induce Adenosine Deaminase 2 mRNA Expression in Monocyte-Derived Macrophages / 결핵및호흡기질환

BACKGROUND: Delayed hypersensitivity plays a large role in the pathogenesis of tuberculous pleural effusion (TPE). Macrophages infected with live Mycobacterium tuberculosis (MTB) increase the levels of adenosine deaminase2 (ADA2) in the pleural fluid of TPE patients. However, it is as yet unclear whether ADA2 can be produced by macrophages when challenged with MTB antigens alone. This study therefore evaluated the levels of ADA2 mRNA expression, using monocyte-derived macrophages (MDMs) stimulated with MTB antigens. METHODS: Purified monocytes from the peripheral blood mononuclear cells of healthy volunteers were differentiated into macrophages using granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF). The MDMs were stimulated with early secretory antigenic target protein 6 (ESAT6) and culture filtrate protein 10 (CFP10). The mRNA expression levels for the cat eye syndrome chromosome region, candidate 1 (CECR1) gene encoding ADA2 were then measured. RESULTS: CECR1 mRNA expression levels were significantly higher in MDMs stimulated with ESAT6 and CFP10, than in the unstimulated MDMs. When stimulated with ESAT6, M-CSF-treated MDMs showed more pronounced CECR1 mRNA expression than GM-CSF-treated MDMs. Interferon-γ decreased the ESAT6- and CFP10-induced CECR1 mRNA expression in MDMs. CECR1 mRNA expression levels were positively correlated with mRNA expression of tumor necrosis factor α and interleukin 10, respectively. CONCLUSION: ADA2 mRNA expression increased when MDMs were stimulated with MTB antigens alone. This partly indicates that pleural fluid ADA levels could increase in patients with culture-negative TPE. Our results may be helpful in improving the understanding of TPE pathogenesis.

Urticaria papular y sus agentes causales en Colombia / Papular urticaria: A review of causal agents in Colombia

Resumen La urticaria papular es una enfermedad alérgica causada por la picadura de insectos, la cual predomina en el trópico. El objetivo de esta revisión fue profundizar en sus aspectos epidemiológicos e inmunológicos, particularmente con base en datos publicados en Latinoamérica. Se hizo una revisión no sistemática mediante la búsqueda electrónica de artículos sobre la epidemiología de la urticaria papular, las características entomológicas de los agentes causales y los mecanismos inmunológicos asociados. Según los diversos reportes de centros médicos de Latinoamérica la urticaria papular es frecuente; el único estudio de prevalencia publicado indica que afecta a una cuarta parte de los niños escolares de Bogotá. Hay información sobre la relación causal entre la exposición domiciliaria a la pulga, la pobreza y la urticaria papular en Bogotá, una ciudad representativa de las altitudes andinas. No hay estudios que indaguen directamente sobre los insectos causales en zonas cálidas, aunque se sospecha clínicamente de los mosquitos Aedes aegypti y Culex quinquefasciatus. En cuanto a su patogenia, se destaca la participación de mecanismos celulares que involucran las células colaboradoras Th2, lo cual explica que sea una condición de hipersensibilidad retardada. El papel de la inmunoglobulina E (IgE) en la urticaria papular no está tan claro. Se desconocen los antígenos derivados de los insectos que causan la enfermedad, aunque se plantea que existen moléculas comunes de reacción cruzada entre los insectos, tales como el alérgeno Cte f 2 en la pulga, y sus homólogos en los mosquitos. La urticaria papular es una condición frecuente en Latinoamérica que debe investigarse en profundidad. La caracterización inmunológica de los componentes moleculares que causan esta condición puede resolver interrogantes sobre su etiología y su patogenia.

Abstract Papular urticaria is a chronic allergic reaction induced by insect bites, which is common in the tropics. The objective of this review was to deepen on epidemiological and immunological aspects of this disease, focused on data published in Latin American countries. We conducted a non-systematic review of the literature through electronic search on the epidemiology of papular urticaria, the entomological characteristics of the causative agents and associated immunological mechanisms. Several reports from medical centers suggest that papular urticaria is common in Latin America. Only one epidemiological survey designed to estimate prevalence of papular urticaria has been published, reporting that about a quarter of children under six years of age is affected by this condition in Bogotá. There is evidence on the causal relationship among exposure to indoor fleas, poverty and papular urticaria in Bogotá, a representative city of the Andean altitudes. Information about causal insects in tropical warmer areas is scarce, although from clinical reports Aedes aegypti and Culex quienquefasciatus appear to be the most common. Th2 cellular-mediated mechanisms are involved in its pathogenesis, which explains its delayed hypersensitivity. The role of immunoglobulin E is not clear in this disease. Insect-derived antigens directly involved in papular urticaria etiology are unknown. However, it is possible that common molecules among causal insects mediate cross-reactive reactions, such as Cte f 2 allergen, found in cat fleas, and its counterparts in mosquitoes. Papular urticaria is a frequent disease in Latin America that should be further investigated. Immunological characterization of the molecular components that cause this condition may solve questions about its pathogenesis.

A novel arctigenin-containing latex glove prevents latex allergy by inhibiting type I/IV allergic reactions / 中国天然药物

The present study aimed at developing a natural compound with anti-allergic effect and stability under latex glove manufacturing conditions and investigating whether its anti-allergic effect is maintained after its addition into the latex. The effects of nine natural compounds on growth of the RBL-2H3 cells and mouse primary spleen lymphocytes were determined using MTT assay. The compounds included glycyrrhizin, osthole, tetrandrine, tea polyphenol, catechin, arctigenin, oleanolic acid, baicalin and oxymatrine. An ELISA assay was used for the in vitro anti-type I/IV allergy screening; in this process β-hexosaminidase, histamine, and IL-4 released from RBL-2H3 cell lines and IFN-γ and IL-2 released from mouse primary spleen lymphocytes were taken as screening indices. The physical stability of eight natural compounds and the dissolubility of arctigenin, selected based on the in vitro pharnacodynamaic screening and the stability evaluation, were detected by HPLC. The in vivo pharmacodynamic confirmation of arctigenin and final latex product was evaluated with a passive cutaneous anaphylaxis (PCA) model and an allergen-specific skin response model. Nine natural compounds showed minor growth inhibition on RBL-2H3 cells and mouse primary spleen lymphocytes. Baicalin and arctigenin had the best anti-type I and IV allergic effects among the natural compounds based on the in vitro pharmacodynamic screening. Arctigenin and catechin had the best physical stability under different manufacturing conditions. Arctigenin was the selected for further evaluation and proven to have anti-type I and IV allergic effects in vivo in a dose-dependent manner. The final product of the arctigenin-containing latex glove had anti-type I and IV allergic effects in vivo which were mainly attributed to arctigenin as proved from the dissolubility results. Arctigenin showed anti-type I and IV allergic effects in vitro and in vivo, with a good stability under latex glove manufacturing conditions, and a persistent anti-allergic effect after being added into the latex to prevent latex allergy.

Ibuprofen induced Stevens-Johnson syndrome

Despite the fact that any drug can be an impending cause of hypersensitivity reactions, Ibuprofen, an over-the-counter drug used extensively as an analgesic and antipyretic in Asia, is considered to be relatively safe. But herein we report a rare extremely 'rapid onset' occurrence of a severe case of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a 22-year-old male, induced by 3 doses of 400 mg of Ibuprofen taken at 8-hour interval for eye pain, probably the first case report of rapid onset of TEN by nonsteroidal antiinflammatory drugs in Nepal. SJS and TEN are idiosyncratic, delayed hypersensitivity inflammatory adverse drug reactions that are severe adverse cutaneous drug reactions which predominantly involve the skin and mucous membranes and are linked with high morbidity and mortality. Nevertheless, removal of ibuprofen and its metabolites with plasma exchange and treatment with antibiotics and intravenous corticosteroids along with supportive therapy improved the course of the disorder. This rare case report addresses the fact that severe hypersensitivity reactions can occur with Ibuprofen, which can be potentially dangerous and life threatening. It is thus important for the clinicians to be alert to such severe hypersensitivity reactions even with drugs which are deemed to be probably safe.

Effect of Modified Danggui Yinzi on Delayed Allergy in Model Mice with Qi-Blood Deficiency Syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of Danggui Yinzi (DY) on delayed allergy in model mice with qi-blood deficiency syndrome (QBDS).</p><p><b>METHODS</b>QBDS model was established in 48 Kuming mice of SPF grade by using reserpine and acetophenone hydrazine. Forty of them were then randomly divided into the model group, the loratadine group, the high dose DY group, the middle dose DY group, and the low dose DY group, 8 in each group. Another 8 in line with the same standard were recruited as a blank group. Mice in high, middle, and low dose DY groups were administered with DY concentrated solution at 60, 30, 15 g/kg by gastrogavage. Mice in the loratadine group were administered with loratadine solution at 1.66 mg/kg by gastrogavage. Equal volume of normal saline was administered to mice in the model group and the blank group by gastrogavage. All medication was given once per day for 1 successive week. Except those in the blank group, the rest mice were evenly smeared with 1% DNCB solution on the abdomen. Five days after skin allergy, 1% DNCB solution was smeared to right ear of all mice to stimulate allergic reaction. Mice in the blank group were smeared in the same way without allergenic reaction. The auricle swelling and the inhibition ratio were determined at 24 h after attack. Blood was collected from orbit and serum IgE level detected using double-antibody sandwich ELISA.</p><p><b>RESULTS</b>Compared with the blank group, auricle swelling obviously increased and serum IgE level was obviously elevated in the model group (P < 0.01). Compared with the model group, auricle swelling obviously decreased and serum IgE level was obviously reduced in the 3 dose DY groups (P < 0.05, P < 0.01). Meanwhile, the auricle swelling degree was superior in high and middle dose DY groups to that in the loratadine group (P < 0.05). The inhibition ratio of auricle swelling was sequenced from high to low as 67.3% in the high dose DY group, 56.0% in the middle dose DY group, 48.1% in the low dose DY group, 47.3% in the loratadine group.</p><p><b>CONCLUSIONS</b>DY could inhibit auricle swelling and lower serum IgE level. It also could inhibit delayed allergic reaction in model mice with QBDS to some extent.</p>

Paradoxical response as a cervical lymph node enlargement after termination of anti-tuberculosis treatment in a patient with pulmonary tuberculosis / 고신대학교의과대학학술지

A paradoxical response is not uncommon in non-HIV-infected patients, particularly those with extra-pulmonary tuberculosis. It is defined as the radiological and clinical worsening of a previous lesion or the development of new lesion during anti-tuberculosis therapy. The paradoxical response has been attributed to host immunologic reactions, such as a delayed hypersensitivity or a response to mycobacterial antigens. In most reports of paradoxical response, these responses occurred in the same location as a previous lesion. In this patient with pulmonary tuberculosis, cervical lymph node enlargement occurred as a paradoxical response after the completion of anti-tuberculosis treatment. Although the new lesion developed in another location, it could be considered as a paradoxical response based on the negative culture result of acid fast bacilli from the new lesion and drug sensitivity result from initial bronchoalveolar lavage specimen. Therefore we were able to decide on the termination of unnecessary anti-tuberculous treatment. Based on our case, we can conclude that paradoxical response can occur after the termination of anti-tuberculosis therapy even in new site.

A Case of Erythema Nodosum Associated with Mycoplasma pneumoniae Infection: Pathologic Findings and a Presumed Pathogenesis

Erythema nodosum (EN) is a painful skin disease characterized by erythematous tender nodules located predominantly over the extensor aspects of the legs. Various etiological factors, including infection, drug administration, and systemic illness have been implicated as causes of EN. Mycoplasma pneumoniae is one of rare infectious agents to cause EN in children. We report a case of a 7-year-old boy with context of respiratory illness and skin lesions with arthralgia. From stepwise approaches, IgM antibody against M. pneumoniae was positive with titers of 12.18, consistent with respiratory infection of M. pneumoniae and histopathology showed findings of septal and lobular inflammation without vasculitis consistent with EN. In addition, we reviewed the pathogenesis of this disease based on our case and the previous reports.

Methazolamide-induced toxic epidermal necrolysis confirmed by lymphocyte activation test

Among various dermatological entities, toxic epidermal necrolysis (TEN) is a rare but potentially fatal delayed hypersensitivity reaction to numerous medications. A 38-year-old male presented with systemic hypersensitivity reaction, such as high fever, pain in the eyes, and diffuse pruritic erythematous maculopapular eruptions with multiple targetoid plaques that became vesicular and bullous. Oral mucosa and conjunctivae were involved. The first sign appeared about 1 week after taking methazolamide (50 mg twice a day) for the management of glaucomatous eyes. Although methazolamide was discontinued, blistering and skin denudation progressed to affect up to 80% of the body surface area and a positive Nikolsky sign was noted. High fever also persisted. Skin lesions started to improve after 2 weeks of management and fever subsided. Cutaneous lesions improved with minimal permanent sequele 2 months later. HLA-B*5901 was found by high-resolution genotyping. The lymphocyte activation test performed 6 months after remission showed a positive response to methazolamide challenge. This is the first case of methazolamide-induced TEN in which methazolamide was confirmed as a culprit drug by the lymphocyte activation test.

Iodinated contrast media-induced fixed drug eruption

Iodinated contrast media (ICM) can cause not only immediate onset hypersensitivity but also delayed onset hypersensitivity. While the most common form of delayed onset hypersensitivity reaction to ICM is exanthematous eruption, fixed drug eruption (FDE) can occur rarely related to ICM. A 70-year-old male with liver cirrhosis and hepatocellular carcinoma repeatedly experienced erythematous patches on his right forearm and hand 6 hours after exposure to iopromide for computed tomography scan. ICM induced FDE was diagnosed clinically. Intradermal test with 6 kinds of ICM (iobitridol, iohexol, iomeprol, iopamidol, iopromide, and iodixanol) was performed and showed the weakest positive reaction to iohexol compared to the others in 48 hours. After changing iopromide to iohexol based on these results, FDE did not recur. We report here a case of iopromide induced FDE which was successfully prevented by changing ICM to iohexol based on intradermal test results.