Paradoxical upgradation response in non-HIV tuberculosis: Report of two cases

A paradoxical upgradation response in tuberculosis (TB) is defined as the worsening of a pre-existing tubercular lesion or the appearance of a new lesion in a patient whose clinical symptoms initially improved with anti-TB treatment. A paradoxical response is common in HIV patients in the form of immune reconstitution inflammatory syndrome. A similar kind of response can also be seen in immunocompetent patients. Here, we present two cases of non-HIV TB who initially improved with antitubercular therapy (ATT) but worsened thereafter. After excluding possibilities such as multidrug-resistant TB, treatment failure or a superadded infection, a paradoxical upgradation response was diagnosed. Both the cases improved after treatment with corticosteroids in addition to ATT.

Paradoxical reactions in antitubercular therapy / 中华实用儿科临床杂志

Some patients with tuberculosis will undergo abnormal deterioration after appropriate anti-tuberculosis treatment, manifested by deterioration of the original lesions or new lesions, known as contradictory reactions, in patients co-infected with human immunodeficiency virus(HIV), this phenomenon is called immune reconstruction inflammatory response syndrome.It is generally believed that the contradictory reaction is an excessive inflammatory reaction, which is related to the host immune response and the direct action of Mycobacterium products.Before diagnosing contradictory reactions, factors such as treatment failure, drug resistance, re-infection, surgical impact and adverse drug events should be excluded.Regulating host immune response is the main way to deal with contradictory reactions.Some patients may need more active treatment.

Paradoxical reactions in antitubercular therapy / 中华实用儿科临床杂志

Some patients with tuberculosis will undergo abnormal deterioration after appropriate anti-tubercu losis treatment,manifested by deterioration of the original lesions or new lesions,known as contradictory reactions,in patients co-infected with human immunodeficiency virus (HIV),this phenomenon is called immune reconstruction inflammatory response syndrome.It is generally believed that the contradictory reaction is an excessive inflammatory reaction,which is related to the host immune response and the direct action of Mycobacterium products.Before diagnosing contradictory reactions,factors such as treatment failure,drug resistance,re-infection,surgical impact and adverse drug events should be excluded.Regulating host immune response is the main way to deal with contradictory reactions.Some patients may need more active treatment.

Paradoxical skin reaction with infliximab treatment / Reação cutânea paradoxal com tratamento com infliximabe

Considering the increased utilization of anti-TNF medications in the treatment of inflammatory and autoimmune diseases, dermatologists should be aware of the possible adverse skin reactions. We describe a case of inverted psoriasis due to the use of infliximab used in the treatment of inflammatory bowel disease. (AU)

Com o aumento do uso de anti-TNF no tratamento de doenças inflamatórias e auto-imunes, os dermatologistas devem estar conscientes da possibilidade de reações cutâneas adversas. Apresentamos um caso de psoríase invertida devido ao uso de infliximab utilizado no tratamento da doença inflamatória intestinal. (AU)

Can A Sudden Sensorineural Hearing Loss Occur Due to Miliary Tuberculosis?

Miliary tuberculosis is a severe form of tuberculosis resulting from dissemination of Mycobacterium tuberculosis bacilli. Since symptoms appearing in patients due to miliary TB are diverse and atypical, depending on the site of invasion, early diagnosis and treatment are important. A paradoxical response of tuberculosis is a rare phenomenon and it can be a clinical difficulty to treatment especially when involving the central nervous system. We present a case report with a review of related literature about the patient who developed sudden hearing loss due to tuberculosis infection in vestibulocochlear area.

Tratamiento de meningitis tuberculosa en paciente HIV negativo, posible reacción paradojal / Possible paradoxical reaction to treatment of tubercular meningitis in an HIV negative patient

La respuesta paradojal al tratamiento tuberculoso es la aparición de manifestaciones clínico-radiológicas nuevas, o el empeoramiento de las previas, luego de una mejoría inicial con el tratamiento específico. Se puede observar en 6-30% de los casos de tuberculosis meníngea. Es una reacción inmunológica exagerada y debe tenerse presente ya que su tratamiento se basa en el uso de inmunomoduladores y no en el cambio de las drogas antituberculosas. Presentamos el caso de una paciente adulta HIV negativa con meningitis tuberculosa que, luego de una adecuada respuesta inicial al tratamiento, intercurre a las 10 semanas con una reacción paradojal tratada satisfactoriamente con corticoides.

The paradoxical response to tuberculosis treatment consists in the appearance of new clinical or radiologic manifestations or worsening of previous injuries after an initial improvement with anti-tuberculosis therapy. It can be observed in 6 to 30 percent of the cases of tubercular meningitis. It is the consequence of an exaggerated immune reaction that should be considered since the treatment is based on the use of immunomodulators and not in the change of anti-tuberculous drugs. We present the case of an HIV negative adult with tuberculous meningitis with a good initial response to specific therapy who showed, 10 weeks later, a paradoxical reaction to treatment that responded successfully to corticosteroids.

Reacción paradójica al tratamiento antituberculosis en una niña inmunocompetente afectada de tuberculosis ganglionar pulmonar / Paradoxical reaction to antituberculosis treatment in an immunocompetent girl with pulmonary tuberculosis

La reacción paradójica al tratamiento antituberculoso es una entidad poco frecuente en pediatría. Se presenta el caso de una niña de 9 años con fiebre, tos y expectoración de tres semanas de evolución. La prueba de tuberculina y Quantiferon fueron positivos; la velocidad de sedimentación era de 64 mm/h; el cultivo y la reacción en cadena de la polimerasa para M. tuberculosis fueron negativos. La radiografía de tórax mostró ensanchamiento mediastínico derecho. Ante el diagnóstico de tuberculosis, se inició un tratamiento con rifampicina, isoniacida, pirazinamida y etambutol en dosis estándar. A los 21 días, reapareció la fiebre elevada sin otra sintomatología, empeoramiento radiológico junto con normalidad de serologías, analítica sanguínea y resonancia cerebral. Se diagnosticó una reacción paradójica; se inició 1 mg/kg/día de prednisona oral, y quedó afebril a las 24 horas. Es importante considerar esta entidad cuando otras causas de empeoramiento clínico y/o radiológico se han descartado para evitar pruebas complementarias y modificaciones de tratamiento innecesarias.

Paradoxical reaction to antituberculosis treatment is rare in paediatric population. We report a 9-year-old girl with high fever and productive cough for the last three weeks. Tuberculine test and Quantiferon were positive, erythrocyte sedimentation rate was 64 mm/h, culture and polymerase chain reaction for M. tuberculosis negative, and chest X ray showed a widened right mediastinum. Tuberculosis was diagnosed, therefore treatment with standard doses of rifampicin, isoniazid, pyrazinamide and ethambutol was started. Twenty-one days later she presented high fever with no other symptoms, worsening of radiological findings and normal blood tests, serologies and brain magnetic resonance imaging. The patient presented a paradoxical reaction and was given prednisone 1 mg/kg/day, fever disappeared in 24 hours. It is important to consider a paradoxical reaction when other causes of clinical and/or radiological worsening have been ruled out, to avoid unnecessary tests and treatment modifications.

A Case of Paradoxical Reaction Development during Antituberculosis Therapy / 대한소화기학회지

Paradoxical reaction during antituberculosis therapy is defined as aggravation of preexisting tuberculous lesions or the development of new lesions. A 24-year-old female college student diagnosed with abdominal and pulmonary tuberculosis presented with fever and abdominal pain after having been treated with antituberculosis agents for 4 months. Tuberculous mesenteric lymphadenitis was suspected on abdominal CT scan and enlarged necrotic abscess was also present. These findings were considered to be due to paradoxical reaction rather than treatment failure during antituberculosis treatment. Although laparoscopic bowel adhesiolysis and abscess drainage were performed, high fever and severe abdominal pain did not improve. However, the patient eventually made a completely recovery after corticosteroid therapy combined with antituberculosis agents. Herein, we report a case of paradoxical reaction which developed in a patient with abdominal and pulmonary tuberculosis during antituberculosis therapy.

Aggression Following Benzodiazepine Ingestion In A Forensic Psychiatric Patient: A Case Report

Objective: The incidence of benzodiazepine paradoxical reaction is uncommon. It may be implicated with crime as will be described in this case report. Method: We report a 37 year-old schizophrenia patient who was detained by the authority under Section 392/397 of Penal Code assaulting a lady using sharp weapon. He had history of illicit substance abuse and benzodiazepine dependence with significant history of aggression associated with benzodiazepine. Just prior to the incident, he took a significant amount of various types of benzodiazepine and suffered from amnesia of that event. During the time of the offense, he was in remission as far as schizophrenia is concerned. Result: He was under the forensic psychiatric care and observation at Hospital Bahagia Ulu Kinta (HBUK). He developed withdrawal symptoms of benzodiazepine in the ward. Conclusion: He was found by the expert team to be under the influence of benzodiazepine during the offence. The role of benzodiazepine and relevant factors leading to aggression will be discussed in this manuscript.

Reacción paradojal en meningitis tuberculosa: presentación de un caso / Paradoxical reaction in tuberculous meningitis: a case report

La afectación del sistema nervioso central es una de las localizaciones extrapulmonares de la tuberculosis con peor pronóstico. El retraso en el diagnóstico y tratamiento es uno de los factores relacionados con mayor tasa de mortalidad y secuelas. Se describe la "reacción paradojal" como un deterioro sintomático de grado variable, durante el tratamiento efectivo de la tuberculosis. El aumento de la resistencia del Mycobacterium tuberculosis a fármacos observado en los últimos años genera mayor preocupación ante la aparición de una reacción paradojal durante el tratamiento. Se presenta el caso de un niño con meningitis tuberculosa que, luego de un mes de tratamiento, presentó empeoramiento clínico y nuevas lesiones en la tomografía y resonancia magnética nuclear de cerebro. Se excluyeron patologías asociadas, se verificó que la toma de medicamentos haya sido supervisada, y la sensibilidad del bacilo a fármacos antituberculosos de primera línea fue confirmada. El paciente no requirió cambios en el esquema de tratamiento antituberculoso y se administraron esteroides para el alivio sintomático. La reacción paradojal durante el tratamiento antituberculoso es infrecuente y debida a una reacción de hipersensibilidad entre el huésped y el bacilo tuberculoso. Cuando aparece, se debe asegurar la efectividad y el cumplimiento del tratamiento administrado.

The central nervous system is one of the locations of extrapulmonary tuberculosis with worse prognosis. The delay in diagnosis and treatment is one of the factors associated with higher mortality and sequelae. The "paradoxical reaction" is described as a variable degree of symptomatic deterioration during the effective treatment of tuberculosis. The increased resistance of Mycobacterium tuberculosis to drugs observed in recent years generates greater concern about the emergence of a paradoxical reaction during treatment. The case of a child with tuberculous meningitis that after one month of treatment presented clinical worsening and new lesions in CT and MRI images of the brain is presented. Comorbidities were excluded, it was verified that taking drugs has been monitored, and the sensitivity of the bacillus to first-line antituberculosis drugs was confirmed. The patient required no change in the pattern of tuberculosis treatment and steroids were administered for symptomatic relief. The paradoxical reaction during antituberculosis treatment is rare and due to a hypersensitivity reaction between the host and the tuberculous bacillus. When it appears you must ensure the effectiveness and compliance of the treatment.

Reacción paradojal al tratamiento antituberculoso en un paciente inmunocompetente: a propósito de un caso / Paradoxical reaction during tuberculosis treatment in immunocompetent children: case report

Tuberculosis is an important public health problem. It is estimated that around 5-10% of patients with tuberculosis present with central nervous system involvement; meningitis and tuberculoma being two of the most frequent manifestations. The paradoxical reaction in patients undergoing antituberculosis treatment is infrequent, nevertheless it is an important consideration in patients, who after an appropriate initial response to specific treatment, present with worsening clinical and radiological signs or the appearance of new lesions.

La tuberculosis (TBC) es un problema de importancia en salud pública. Se estima que alrededor de 5 a 10% de los pacientes con TBC presentan compromiso de sistema nervioso central, siendo la meningitis y el tuberculoma las manifestaciones más frecuentes. La reacción paradojal en pacientes con tratamiento antituberculoso es infrecuente, sin embargo, es importante considerarla en pacientes que durante la terapia, luego de una respuesta inicial apropiada, presentan un empeoramiento clínico y/o radiológico o aparición de nuevas lesiones.

The effect of midazolam dose and age on the paradoxical midazolam reaction in Korean pediatric patients / 대한마취과학회지

BACKGROUND: Although midazolam administration may occasionally induce a paradoxical episode, such as threatened crying and violent behavior in children, systematic studies on the causes of paradoxical reaction are limited. We investigated the effect of children's age and a dose of midazolam on the paradoxical reaction. METHODS: A total of one hundred sixty four children of 1-3 years and 3-5 years, were enrolled in this study. Each age group randomly received 0.05 mg/kg or 0.1 mg/kg of intravenous midazolam (41 patients/group). RESULTS: The incidence of paradoxical midazolam reaction in the study groups, 1-3 years with 0.1 mg/kg of intravenous midazolam, 1-3 years with 0.05 mg/kg, 3-5 years with 0.1 mg/kg, and 3-5 years with 0.05 mg/kg were as follows: 29.3%, 12.2%, 7.3% and 2.4%, respectively. The incidence among the 4 groups was significantly different (P = 0.002), highest in the 1-3 years receiving 0.1 mg/kg of midazolam (29.3%). Both age (P = 0.004, OR [95%CI] = 5.3 [1.7-16.8]) and dose of midazolam (P = 0.036, OR [95%CI] = 3.0 [1.1-8.4]) were risk factors. Perioperative clinical data including anxiety scales of children were not associated with the paradoxical midazolam reaction. CONCLUSIONS: In conclusion, we suggest that children less than 3 years old receiving higher dose of intravenous midazolam are at risk for the paradoxical midazolam reaction.

Rebound effect of drugs: fatal risk of conventional treatment and parmacological basis of homeopathic treatment / Efeito rebote das drogas: riscos fatais do tratamento convencional e bases farmacológicas do tratamento homeopático / Efecto rebote de drogas: riesgos fatales del tratamiento convencional y bases farmacológicas del tratamiento homeopático

The homeopathic model applies the secondary action or vital reaction of the organism as a therapeutic method and thus prescribes treatment by similitude, which consists in administering to ill individuals substances that cause similar symptoms in healthy individuals. The vital, homeostatic or paradoxical reaction of the organism might be explained scientifically by means of the rebound effect of modern drugs, which might cause fatal iatrogenic events after discontinuation of antipathic (a term used in alternative medicine for palliative treatment, also known as enantiopathic) treatment. Although the rebound effect is studied by modern pharmacology, it is poorly communicated to and discussed among healthcare professionals, who are thus deprived of information needed for the safe management of modern drugs. This article presents an up-to-date review on the rebound effect of modern drugs that grounds the homeopathic principle of healing and calls the attention of doctors to this type of adverse effect that is usually unnoticed. The rebound effect of modern palliative drugs, which was pointed out by Hahnemann more than two centuries ago, might cause fatal adverse events and is illustrated by the examples of acetylsalicylic acid, anti-inflammatory agents, bronchodilators, antidepressants, statins, proton-pump inhibitors, etc. Although the rebound effect is expressed by a small fraction of (susceptible) individuals and might be avoided by gradual tapering of antipathic drugs, it exhibits epidemiologic importance as a function of the massive use of such palliative drugs and the lack of knowledge in its regard.

O modelo homeopático aplica a ação secundária ou reação vital do organismo como método terapêutico. Assim, propõe o tratamento por semelhança, que consiste em administrar aos doentes substâncias que produzem sintomas similares em pessoas sadias. A reação vital, homeostática ou paradoxal do organismo pode ser explicada cientificamente com base no efeito rebote das drogas modernas. Este pode produzir eventos iatrogênicos fatais depois da suspensão do tratamento antipático (ou enantiopático, termo utilizado em medicina alternativa para se referir ao tratamento paliativo). Embora o efeito rebote é abordado pela farmacologia moderna, é pouco difundido e discutido pelos profissionais da saúde que, assim, são privados de informação necessária para o manejo seguro das drogas modernas. Este artigo apresenta uma revisão atualizada do efeito rebote das drogas modernas e que também embasa o princípio homeopático da cura. Apontado por Hahnemann mais de dois séculos atrás, o efeito rebote das drogas paliativas modernas pode causar efeitos adversos fatais, como ilustram os exemplos do ácido salicílico, anti-inflamatórios, broncodilatadores, antidepressivos, estatinas, inibidores da bomba de prótons, etc. Embora o efeito rebote seja expressado por uma pequena parte de indivíduos (suscetíveis) e possa ser evitando através da retirada gradual das drogas antipáticas, atinge importância epidemiológica devido ao uso maciço dessas drogas e do desconhecimento a seu respeito.

A study of TB-associated immune reconstitution inflammatory syndrome using the consensus case-definition.

Background & objectives: A considerable proportion of patients with HIV associated tuberculosis (TB) started on highly active antiretroviral therapy (HAART) develop immune reconstitution inflammatory syndrome (IRIS), which is difficult to diagnose in a resource-limited setting. In view of the recently proposed consensus case-definitions for TB-IRIS for use in resource-limited settings we undertook this study to describe the incidence and risk factors of TB associated IRIS in a tertiary care hospital and research centre in north India. Methods: Retrospective analysis of antiretroviral treatment (ART) naïve adults started on highly active ART (HAART) from June 2006 to September 2008 was done. Results: Of the 627 patients studied, 237 (38%) had TB at the initiation of HAART. In total, 18 (7.5%) of 237 patients with TB at baseline had paradoxical TB-associated IRIS, and 12 (3%) of 390 patients without TB at baseline developed ART-associated TB. Most IRIS events occurred during the initial 30 days of HAART. Two patients developed TB-associated IRIS after 90 days of HAART. Using univariate analysis, low CD4+ cell count at baseline [64 (28-89) vs. 95 (52-150); P=0.009] and early initiation of HAART [33 (24-41) vs. 48 (35-61) days; P<0.001] were significantly associated with paradoxical TB-associated IRIS. No identifiable risk factors were associated with the development of ART-associated TB. Interpretation & conclusions: A considerable proportion of patients on HAART develop TB-associated IRIS. The consensus case-definition is a useful tool in resource-limited settings for the diagnosis of TB-associated IRIS.

A Case of Obstructive Jaundice Caused by Paradoxical Reaction during Antituberculous Chemotherapy for Abdominal Tuberculosis

Abdominal tuberculosis is not a rare disease, but obstructive jaundice caused by tuberculosis (tuberculous lymphadenitis, tuberculous enlargement of the head of pancreas, and/or tuberculous stricture of the biliary tree) is rare. We recently experienced a case of obstructive jaundice as a result of paradoxical reaction of periportal tuberculous lymphadenopathy that was treated successfully with corticosteroid and biliary drainage. No similar cases have been reported previously.

Severe Paradoxical Reaction Requiring Tracheostomy in a Human Immunodeficiency Virus (HIV)-negative Patient with Cervical Lymph Node Tuberculosis

During drug treatment of tuberculous lymphadenitis, paradoxical response (PR) may occasionally occur. Continued treatment or lymph node aspiration improves PR without severe sequelae. However, we report a case of severe PR in a patient with cervical lymph node tuberculosis causing airway obstruction due to retropharyngeal lymph node swelling during antituberculous treatment. Tracheostomy and drainage of the node were performed to secure the airway. Possible airway obstruction due to PR must be suspected when cervical lymph node tuberculosis involves the retropharyngeal lymph node.

Immune reconstitution syndrome in patients treated for HIV and tuberculosis in Rio de Janeiro

We made a retrospective longitudinal study from January 2000 to January 2003 to examine cases of immune reconstitution syndrome (IRS) and its incidence rate in tuberculosis (TB)-human immunodeficiency virus (HIV) co-infected patients. The incidence rate (IR) was calculated using a Poisson regression. The confidence interval (CI) that was stipulated was 95 percent. IRS occurred in 10/84 HIV and TB-positive patients; nine of them were on highly active anti-retroviral therapy (HAART) during a mean of 61.7 (±59) days following the introduction of antiretrovirals. Lymph-node enlargement was the sole clinical manifestation. CD4 counts were <100 cells/mm³in 50 percent of the patients, at the time of TB diagnosis. All but two patients were treated with prednisone, and recovered from TB within a mean of 91 days (±30 days). One relapse of TB was observed, but there were no IRS-related deaths. The incidence rate was higher (IR=11.18; CI, 1.41-88.76) in patients that had superficial lymph node enlargement at the moment of TB diagnosis (not associated with TB), extrapulmonary TB (IR=1.97; CI, 0.44-8.79), were antiretroviral naive (IR=1.85; CI, 0.48-7.16), and CD4 counts <100 cells/mm³ (IR=1.50; CI, 0.40-5.59), although with a wide CI. IRS was frequent in our sample, occurred more frequently in HIV-naive patients with lymph-node enlargement and extrapulmonary TB. No cases of new pulmonary lesions or worsening of pulmonary infiltrates were observed.

Predictable Factors for Paradoxical Reactions in Conscious Sedation with Midazolam During ERCP / 대한소화기내시경학회지

BACKGROUND/AIMS: Paradoxical reaction after midazolam administration is relatively uncommon and can obstruct the performance of ERCP. But it can not be predicted before drug administration. We investigate the difference in occurrence of paradoxical reaction according to personal characteristics and clinical status of patients. METHODS: During 155 ERCP procedures, we injected midazolam and meperidine intravenously for conscious sedation until deep sleep occurred. Among 155 patients, 108 patients did not showed paradoxical reaction (group I) and 47 patients (30.3%) showed gross behavioral disturbance and/or agitation (group II). Paradoxical agitation was seen in 9 (7.1%) procedures. RESULTS: Type A-like personality (p=0.002), sleep-talking habit (p=0.026) and presence of pain at the beginning of ERCP (p=0.036) and during ERCP (p=0.021) were seen more frequently in group II. Duration of ERCP was longer (p=0.034) and dosage of midazolam was larger (p=0.009) in group II. In multivariate analysis, having sleep-talking (OR, 5.5), type A-like personality (OR 3.9) and dosage of midazolam (OR 1.3) were risk factors of paradoxical reaction. CONCLUSIONS: Paradoxical agitation after midazolam administration was uncommon and can be managed with flumazenil. Paradoxical reaction can be predicted more often in patients with type A-like personality, sleep-talking habit, complaining pain before ERCP, and in patients injected large dosage of midazolam.