Adults with excess weight or obesity, but not with overweight, report greater pain intensities than individuals with normal weight: a systematic review and meta-analysis.

Context: Over 1.9 billion adult people have overweight or obesity. Considered as a chronic disease itself, obesity is associated with several comorbidities. Chronic pain affects approximately 60 million people and its connection with obesity has been displayed in several studies. However, controversial results showing both lower and higher pain thresholds in subjects with obesity compared to individuals with normal weight and the different parameters used to define such association (e.g., pain severity, frequency or duration) make it hard to draw straight forward conclusions in the matter. The objective of this article is to examine the relationship between overweight and obesity (classified with BMI as recommended by WHO) and self-perceived pain intensity in adults. Methods: A literature search was conducted following PRISMA guidelines using the databases CINAHL, Cochrane Library, EMBASE, PEDro, PubMed, Scopus and Web of Science to identify original studies that provide BMI values and their associated pain intensity assessed by self-report scales. Self-report pain scores were normalized and pooled within meta-analyses. The Cochrane's Q test and I2 index were used to clarify the amount of heterogeneity; meta-regression was performed to explore the relationship between each outcome and the risk of bias. Results: Of 2194 studies, 31 eligible studies were identified and appraised, 22 of which provided data for a quantitative analysis. The results herein suggested that adults with excess weight (BMI ≥ 25.0) or obesity (BMI ≥ 30.0) but not with overweight (pre-obesity) alone (BMI 25.0-29.9), are more likely to report greater intensities of pain than individuals of normal weight (BMI 18.5-24.9). Subgroup analyses regarding the pathology of the patients showed no statistically significant differences between groups. Also, influence of age in the effect size, evaluated by meta-regression, was only observed in one of the four analyses. Furthermore, the robustness of the findings was supported by two different sensitivity analyses. Conclusion: Subjects with obesity and excess weight, but not overweight, reported greater pain intensities than individuals with normal weight. This finding encourages treatment of obesity as a component of pain management. More research is required to better understand the mechanisms of these differences and the clinical utility of the findings. Systematic Review Registration: https://doi.org/10.17605/OSF.IO/RF2G3, identifier OSF.IO/RF2G3.

Investigational Drugs for the Treatment of Postherpetic Neuralgia: Systematic Review of Randomized Controlled Trials.

The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.

Reply to Rossettini et al. "Do Not Mix Apples with Oranges" to Avoid Misinterpretation of Placebo Effects in Manual Therapy: The Risk Is Resulting in a Fruit Basket. Comment on "Molina-Álvarez et al. Manual Therapy Effect in Placebo-Controlled Trials: A Systematic Review and Meta-Analysis. Int. J. Environ. Res. Public Health 2022, 19, 14021".

We have thoroughly reviewed and carefully analyzed the points raised in the comment titled: "Do not mix apples with oranges" to avoid misinterpretation of placebo effects in manual therapy: the risk is resulting in a fruit basket [...].

Positive correlational shift between crevicular antimicrobial peptide LL-37, pain and periodontal status following non-surgical periodontal therapy. A pilot study.

BACKGROUND: Periodontitis has a high prevalence and uncertain recurrence. Unlike the pro-inflammatory cytokine profile, little is known about the anti-inflammatory cytokine and antimicrobial peptide overview following treatment. The present study aimed to evaluate if any of the antimicrobial peptide LL-37, interleukin (IL) 4, 10 and 6 together with the volume of gingival crevicular fluid (GCF) and total protein concentration in GCF could be used as correlative biomarkers for the severity in periodontitis as well as prognostic factors in the management of the disease. METHODS: Forty-five participants were recruited and allocated to the healthy (15), Stage I-II (15) or Stage III-IV periodontitis (15) group. Along with periodontal examination, GCF samples were obtained at baseline and 4-6 weeks following scaling and root planing (SRP) for the periodontitis groups. GCF samples were analyzed by ELISA kits to quantify LL-37 and IL-4, -6 and - 10. One-way ANOVA followed by Dunnett's test was used to determine differences among the three groups at baseline. Two-way ANOVA followed by Sidak's post-hoc test was used to compare between pre- and post-SRP in the two periodontitis groups. RESULTS: The amount of GCF volume was significantly correlated to the severity of periodontitis and decreased following SRP, particularly in the Stage III-IV group (p < 0.01). The levels of LL-37, IL-6, and pain and periodontal clinical parameters were significantly correlated to the severity of periodontitis. IL-4 and IL-10 in the periodontitis groups were significantly lower than the healthy group (p < 0.0001) and barely improved following SRP up to the level of the healthy group. CONCLUSIONS: With the limitations of this study, crevicular LL-37 may be a candidate for a biomarker of periodontitis and the associated pain upon probing. TRIAL REGISTRATION: The study was registered in clinical trials.gov, with number NCT04404335, dated 27/05/2020.

Manual Therapy Effect in Placebo-Controlled Trials: A Systematic Review and Meta-Analysis.

PURPOSE: Background: Evaluate whether the design of placebo control groups could produce different interpretations of the efficacy of manual therapy techniques. METHODS: Nine databases were searched (EMBASE, CINAHL, PsycINFO, MEDLINE, PubMed, SCOPUS, WEB of SCIENCE, COCHRANE, and PEDro). Randomized placebo-controlled clinical trials that used manual therapy as a sham treatment on subjects suffering from pain were included. Data were summarized qualitatively, and meta-analyses were conducted with R. RESULTS: 53 articles were included in the qualitative analysis and 48 were included in the quantitative analyses. Manipulation techniques did not show higher effectiveness when compared with all types of sham groups that were analyzed (SMD 0.28; 95%CI [-0.24; 0.80]) (SMD 0.28; 95%CI [-0.08; 0.64]) (SMD 0.42; 95%CI [0.16; 0.67]) (SMD 0.82; 95%CI [-0.57; 2.21]), raising doubts on their therapeutic effect. Factors such as expectations of treatment were not consistently evaluated, and analysis could help clarify the effect of different sham groups. As for soft tissue techniques, the results are stronger in favor of these techniques when compared to sham control groups (SMD 0.40; 95%CI [0.19, 0.61]). Regarding mobilization techniques and neural gliding techniques, not enough studies were found for conclusions to be made. CONCLUSIONS: The literature presents a lack of a unified placebo control group design for each technique and an absence of assessment of expectations. These two issues might account for the unclear results obtained in the analysis.

Antinociceptive and modulatory effect of pathoplastic changes in spinal glia of a TLR4/CD14 blocking molecule in two models of pain in rat.

The role of spinal glia in the development and maintenance of chronic pain has become over the last years a subject of increasing interest. In this regard, toll-like receptor 4 (TLR4) signaling has been proposed as a major trigger mechanism. Hence, in this study we explored the implications of TLR4 inhibition in the periphery and primarily in the CNS, focusing on the impact this inhibition renders in pain development and glia activation in the dorsal horn in two models of pain. Making use of a synthetic cluster of differentiation 14 (CD14)/TLR4 antagonist, the effect of TLR4 blockade on tactile allodynia and heat hyperalgesia was evaluated in osteoarthritic and postoperative rat models. An in vitro parallel artificial membrane permeation assay was performed to determine the proneness of the drug to permeate the blood-brain barrier prior to systemic and central administration. Findings suggest a dominant role of peripheral TLR4 in the model of incisional pain, whilst both peripheral and central TLR4 seem to be responsible for osteoarthritic pain. That is, central and peripheral TLR4 may be differently involved in the etiopathology of diverse types of pain what potentially seems a promising approach in the management of pain.

TLR4 Antagonism Reduces Movement-Induced Nociception and ATF-3 Expression in Experimental Osteoarthritis.

INTRODUCTION: Toll-like receptor 4 (TLR4) is a pattern recognition receptor involved in the detection of pathogen-associated molecular patterns (PAMPs), but also a "danger-sensing" receptor that recognizes host-derived endogenous molecules called damage-associated molecular patterns (DAMPs). The involvement of TLR4 in rheumatic diseases is becoming evident, as well as its potential role as a target for therapeutic intervention. Moreover, increasing evidence also suggests that TLR4 is implicated in chronic pain states. Thus, in this study, we evaluated whether a systemic administration of a synthetic antagonist of TLR4 (TLR4-A1) could decrease nociception and cartilage degradation in experimental osteoarthritis (OA). Furthermore, as the activation transcription factor (ATF)-3 serves as a negative regulator for TLR4-stimulated inflammatory response, we also evaluated the effect of TLR4 inhibition on ATF-3 expression in primary afferent neurons at the dorsal root ganglia (DRG). METHODS: OA was induced in adult male Wistar rats through an intra-articular injection of 2 mg of sodium mono-iodoacetate (MIA) into the left knee. From days 14 to 28 after OA induction, animals received an intraperitoneal injection of either TLR4-A1 (10 mg/kg) or vehicle. Movement- and loading-induced nociception was evaluated in all animals, by the Knee-Bend and CatWalk tests, before and at several time-points after TLR4-A1/vehicle administration. Immunofluorescence for TLR4 and ATF-3 was performed in L3-L5 DRG. Knee joints were processed for histopathological evaluation. RESULTS: Administration of TLR4-A1 markedly reduced movement-induced nociception in OA animals, particularly in the Knee-Bend test. Moreover, the increase of ATF-3 expression observed in DRG of OA animals was significantly reduced by TLR4-A1. However, no effect was observed in cartilage loss nor in the neuronal cytoplasmic expression of TLR4 upon antagonist administration. CONCLUSION: The TLR4 antagonist administration possibly interrupts the TLR4 signalling cascade, thus decreasing the neurotoxic environment at the joint, which leads to a reduction in ATF-3 expression and in nociception associated with experimental OA.

Clusterin: Always protecting. Synthesis, function and potential issues.

In the last years, clusterin, a challenging and paradoxical apolipoprotein, has been of growing interest amongst a rising number of scientists. This enigmatic protein is present in all fluids of the organism besides within the intracellular matrix, and it plays diverse, and at times contrary, roles in a growing number of pathologies. It seems to vary its location and function to assure cellular survival being cytoprotective hence its significance in neuroprotection and cancer along with chemotherapy resistance. However, it can also lead to cellular arrest and its modulation to apoptosis. Additionally, it has been described to modulate pain, as well as linked to inflammation, cardioprotection, satiety and hunger, and possibly to addictive behaviour development. Thus, it has been postulated to be used both as a biomarker and a very explorable new therapeutic target for several conditions.

Toll-like receptor 4: A promising crossroads in the diagnosis and treatment of several pathologies.

Toll-like receptor 4 (TLR4) is expressed in a wide variety of cells and is the central component of the mammalian innate immune system. Since its discovery in 1997, TLR4 has been assigned an ever-increasing number of functions that extend from pathogen recognition to tissue damage identification and promotion of the intrinsic "damage repair response" in pain, intestinal, respiratory and vascular disorders. Precisely, the finding of conserved sequence homology among species along with the molecular and functional characterisation of the TLR4 gene enabled researchers to envisage a common operating system in the activation of innate immunity and the initiation of plastic changes at the onset of chronic pain. Malfunctioning in other conditions was conceived in parallel. In this respect, "pivot" proteins and pathway redundancy are not just evolutionary leftovers but essential for normal functioning or cell survival. Indeed, at present, TLR4 single nucleotide polymorphisms (SNP) and their association with certain dysfunctions and diseases are being confirmed in different pools of patients. However, despite its ability to trigger pathogen infection or alternatively tissue injury communications to immune system, TLR4 targeting might not be considered a panacea. This review article represents a compilation of what we know about TLR4 from clinics and basic research on the 20th anniversary of its discovery. Understanding how to fine-tune the interaction between TLR4 and its specific ligands may lead in the next decades to the development of promising new treatments, reducing polypharmacy and probably having an impact on drug use in numerous pathologies.

Comparison of the antinociceptive profiles of morphine and oxycodone in two models of inflammatory and osteoarthritic pain in rat.

Oxycodone and morphine are two opioid drugs commonly used for the treatment of moderate to severe pain. However, their use in the management of noncancer pain remains a controversial issue and, in this respect, the evidence on their effectiveness and safety, particularly in osteoarthritis, is being questioned. In order to analyse their analgesic profile, two different pain models in rats were used: the formalin-induced inflammatory pain and the monosodium iodoacetate (MIA)-induced knee osteoarthritic pain. Drugs were administered systemically (i.p.) and their antinociceptive effect and potency were assessed. In the formalin test, both morphine and oxycodone produced a dose-dependent antinociceptive effect, but oxycodone outdid morphine in terms of effectiveness and potency (nearly two times) in the early (acute nociceptive) as in the late phase (inflammatory). In the osteoarthritis model, both drugs reduced movement-evoked pain (knee-bend test), mechanical allodynia (von Frey test) and heat hyperalgesia (Plantar test). Pretreatment with naloxone and naloxone methiodide reduced morphine and oxycodone effects. Peripheral mu-opioid receptors play a crucial role in the antinociceptive effect of both drugs on movement-evoked pain and heat hyperalgesia, but not on tactile allodynia. The main finding of our study is that oxycodone has a better antinociceptive profile in the inflammatory and osteoarthritic pain, being more effective than morphine at 14 days post-MIA injection (phase with neuropathic pain); it overcame the morphine effect by improving the movement-induced pain, tactile allodynia and heat hyperalgesia. Therefore, oxycodone could be an interesting option to treat patients suffering from knee osteoarthritis when opioids are required.

Papillitis and neuroretinitis of tuberculous etiology. / Papilitis y neurorretinitis de etiología tuberculosa.

A 57-year-old man with miliary tuberculosis reported visual loss in his right eye, a month after starting a four-drug antituberculous treatment regimen. On exploration, an inferior segmental optic disc edema was objectived and it was attributed to ischemic aetiology. Ethambutol was withdrawn and 60mg of oral prednisone daily were given with a tapering dosage. One and a half months later, he presented a sudden loss of vision in his left eye. In fundoscopy, a papillary edema accompanied by a foveal neurosensory detachment was observed but with no more accompanying uveitic signs. Treatment was intensified with moxifloxacin and corticosteroids were reduced, showing a resolution of the macular detachment but with optic atrophy. Isolated tuberculous involvement of the optic nerve may possible in the context of miliary tuberculosis. In this case, the adopted therapeutic approach to the initial papillitis, which was interpreted as ischemic, could favour the appearance of a neuroretinitis in the fellow eye.

Leishmaniasis cutánea / Cutaneous leishmaniasis

Las leishmaniasis son enfermedades causadas por protozoos del género Leishmania. España es uno de los países en los que la leishmaniasis es endémica. Los casos adquiridos en nuestro país (tanto cutáneos como viscerales) se deben a Leishmania infantum, pero puede haber otros causados por otras especies en viajeros o inmigrantes. Las lesiones cutáneas aparecen fundamentalmente en áreas expuestas y tienden a la curación espontánea dejando cicatriz. El diagnóstico es difícil por la inespecificidad de la clínica y el lento crecimiento del parásito en cultivo. Existen distintas opciones terapéuticas, por lo que cada caso debe ser valorado individualmente según las características de la lesión, la especie causante y el potencial de afectación mucosa. En nuestro país, la primera línea de tratamiento está constituida por los antimoniales pentavalentes intralesionales. En casos refractarios o con riesgo de diseminación mucosa debe emplearse un tratamiento sistémico (AU)

Leishmaniasis are a group of diseases caused by protozoa of the genus Leishmania. Spainis one of the countries where leishmaniasis is endemic. All cases acquired in our country(both cutaneous and visceral) are caused by Leishmania infantum, although cases due to other species may appear in travelers or immigrants. Cutaneous lesions appear mainly in exposed areas and tend to heal spontaneously leaving scars. Diagnosis is often difficult due to the non-specific clinical manifestations and the slow growth of the parasite when cultured. There are different available treatment options and each case should be individually considered,taking into account the characteristics of the lesion, the species of Leishmania and the potential for mucosal spread. In Spain, intralesional pentavalent antimonials are the first-line therapeutic option. In those cases at risk for mucosal dissemination or refractory to local therapy,systemic treatment must be given (AU)

Síndrome de escaldadura estafilocócia en un neonato / Staphylococcal scalded síndrome in a newborn

Se presenta un caso de escaldadura estafilocócica en un neonato de 12 días. El diagnóstico es principalmente clínico, basado en las lesiones cutáneas características (signo de Nikolski). La inmadurez fisiológica del neonato hace necesarios un diagnóstico y tratamiento precoces (AU)

A case of staphylococcal scalded syndrome in a 12 day old newborn is presented. The diagnosis is principally clinical, based on the characteristic skin lesions (Nikolski sign). The physiological immaturity of the newborn makes an early diagnosis and treatment necessary (AU)

[Increase in the incidence of bacterial pneumonia between 2001 and 2004]. / Incremento de la incidencia de neumonía bacteriana entre 2001 y 2004.

AIM: To study patients with typical community-acquired pneumonia (CAP) admitted to our hospital between 2001 and 2004 in order to analyze the incidence of this disease in our health area during this period. METHODS: A retrospective study was performed of patients with CAP admitted to our hospital from 2001 to 2004. Only those patients who fulfilled the criteria for typical pneumonia of possible bacterial origin based on clinical and radiological features and laboratory data were included. The annual incidence rates of CAP were analyzed using demographic data from our health area and from all children admitted to the infectious diseases unit of our hospital during this period. RESULTS: During the study period, 569 children were diagnosed with typical CAP: 116 in 2001, 133 in 2002, 154 in 2003 and 166 in 2004. The incidence rate was 1.3 cases/1,000 children under 14 years old/year in 2001, 1.51 in 2002, 1.69 in 2003 and 1.72 in 2004. These findings represent an increment of 25% in the incidence per 1,000/children/year and an increment of 53% in the incidence per 100 children admitted to our unit. Blood cultures were performed before antibiotic therapy was administered in 487 patients and were positive in 22 (4.5%). Streptococcus pneumoniae was isolated in 21 patients and Streptococcus pyogenes in one. Chest radiographs revealed lobar consolidation in 95% of the patients and 15 % developed pleural effusion. CONCLUSIONS: Cases of CAP of probable pneumococcal etiology increased in our health area during the study period. The number of complicated cases also increased.

[Staphylococcal scalded skin syndrome]. / Síndrome de escaldadura estafilocócica.

INTRODUCTION: Staphylococcal scalded skin syndrome is a rare disease caused by Staphylococcus aureus that produces exfoliative toxins. There are few epidemiological data in our environment. PATIENTS AND METHODS: We present an observational cohort study. We review the cases of staphylococcal scalded skin syndrome monitored at La Paz Children Hospital during the last ten years (January 1997 to December 2006). RESULTS: We obtained 26 patients, 7 in the first 5 years and 19 more in the following years. The mean age at diagnosis was 19 months. Four cases (15%) occurred during the neonatal period. Sixty-seven percent of the cases were diagnosed during spring and summer. Main clinical signs were: erythroderma with blisters and posterior desquamation (100%), perioral fissures (54%), fever (46%), conjunctivitis (42%) and palpebral edema (31%). No significant increases in leukocytes (mean: 11,341/.l) or C-reactive protein (mean: 9 mg/l) were found on blood analysis. Diagnosis was made by clinical findings. S. aureus was isolated in nasal or conjunctival samples on 59% of cases. All strains were sensitive to cloxacillin, clindamycin and vancomycin. The patients were treated with cloxacillin with good progress. CONCLUSIONS: Staphylococcal scalded skin syndrome seems to be more common in the last few years. It must be suspected in children with acute erythroderma and perioral or conjunctival lesions. Treatment with cloxacillin leads to healing without sequelae.

Incremento de la incidencia de neumonía bacteriana entre 2001 y 2004 / Increase in the incidence of bacterial pneumonia between 2001 and 2004

Objetivo: Estudiar los pacientes ingresados en nuestro hospital por neumonía típica adquirida en la comunidad (NAC) en los últimos 4 años y analizar la incidencia en este período. Métodos: Se seleccionaron retrospectivamente todas las NAC ingresadas en nuestro hospital entre los años 2001 y 2004. Se analizaron exclusivamente aquellas que cumplían criterios clínico-analítico-radiológicos de neumonía típica de posible origen bacteriano. Se analiza la incidencia de NAC según los datos de población de nuestra área sanitaria y del número de ingresos totales en la unidad de enfermedades infecciosas. Resultados: Se diagnosticaron un total de 569 NAC que cumplían criterios de bacteriana: 116 casos en 2001, 133 casos en 2002, 154 casos en 2003 y 166 casos en 2004. La incidencia fue de 1,38 casos/1.000 niños < 14 años de edad/año en 2001, 1,51 en 2002, 1,69 en 2003 y 1,72 en 2004. Esto supone un incremento de la incidencia del 25 % por 1.000 niños/año en nuestra área sanitaria y un incremento de la incidencia del 53 % por 100 ingresos en la unidad. Se realizó hemocultivo antes de la antibioterapia en 487 casos, de los cuales fueron positivos 22 (4,5 %), 21 para Streptococcus pneumoniae y 1 para Streptococcus pyogenes. El 95 % de los pacientes presentaba en la radiografía de tórax una imagen de consolidación. El 15 % de los pacientes tuvo derrame pleural. Conclusiones: En los últimos años hemos observado un aumento del número de casos de neumonía de posible origen neumocócico en España, al mismo tiempo que también se ha producido un incremento de los casos complicados (AU)

Aim: To study patients with typical community-acquired pneumonia (CAP) admitted to our hospital between 2001 and 2004 in order to analyze the incidence of this disease in our health area during this period. Methods: A retrospective study was performed of patients with CAP admitted to our hospital from 2001 to 2004. Only those patients who fulfilled the criteria for typical pneumonia of possible bacterial origin based on clinical and radiological features and laboratory data were included. The annual incidence rates of CAP were analyzed using demographic data from our health area and from all children admitted to the infectious diseases unit of our hospital during this period. Results: During the study period, 569 children were diagnosed with typical CAP: 116 in 2001, 133 in 2002, 154 in 2003 and 166 in 2004. The incidence rate was 1.3 cases/1,000 children under 14 years old/year in 2001, 1.51 in 2002, 1.69 in 2003 and 1.72 in 2004. These findings represent an increment of 25 % in the incidence per 1,000/children/year and an increment of 53 % in the incidence per 100 children admitted to our unit. Blood cultures were performed before antibiotic therapy was administered in 487 patients and were positive in 22 (4.5 %). Streptococcus pneumoniae was isolated in 21 patients and Streptococcus pyogenes in one. Chest radiographs revealed lobar consolidation in 95 % of the patients and 15 % developed pleural effusion. Conclusions: Cases of CAP of probable pneumococcal etiology increased in our health area during the study period. The number of complicated cases also increased (AU)

[Multidrug-resistant tuberculosis in the pediatric age group]. / Tuberculosis mutirresistente en la edad pediátrica.

AIMS: To study the clinical and epidemiological features in eight pediatric patients with multidrug-resistant tuberculosis (MDR-TB) diagnosed from 1994 to 2005 in three hospitals in Madrid (Spain). METHODS: A retrospective study was performed in patients aged less than 15 years old with positive culture for multidrug-resistant Mycobacterium tuberculosis and patients with negative cultures diagnosed after contact with MDR-TB. RESULTS: Pulmonary tuberculosis was diagnosed in seven patients and arthritis in one. Fifty percent of the patients were immigrants and an adult source case was found in four (50%). M. tuberculosis was isolated in gastric juice in four patients and in synovial biopsy in one. In three patients cultures were negative but these patients had previously been in contact with MDR-TB. Two strains were resistant to isoniazid and rifampicin, four were resistant to isoniazid, rifampicin and streptomycin, one was resistant to isoniazid, rifampicin, streptomycin and pyrazinamide, and one was resistant to 11 drugs. Six patients initially received conventional treatment without improvement. Patients received therapy for 15 months (range: 12 to 18) with 3 to 5 drugs according to the sensitivity study. The following adverse effects were observed: creatine phosphokinase increase (one patient), tendinitis (one patient), alteration of visual evoked responses (one patient) and transitory psychosis (one patient). One patient required pulmonary lobectomy. All patients responded satisfactorily to medical treatment. CONCLUSIONS: MDR-TB should be suspected in patients not responding to TB treatment, especially those from countries with high resistance rates. In patients with negative cultures, treatment should rely on the results of a sensitivity study in the adult source case. MDR-TB requires the use of second-line anti-TB drugs for prolonged periods with possible toxic effects.

Tuberculosis mutirresistente en la edad pediátrica / Multidrug-resistant tuberculosis in the pediatric age group

Objetivos Estudiar las características clínicas y epidemiológicas de 8 pacientes pediátricos con tuberculosis multirresistente (TB-MDR) diagnosticados en 3 hospitales de Madrid entre 1994 y 2005. Métodos Estudio retrospectivo que incluye pacientes menores de 15 años con aislamiento de Mycobacterium tuberculosis multirresistente y sin aislamiento que empezaron tras contacto con TB-MDR. Resultados Se diagnosticaron 7 tuberculosis pulmonares y una artritis. El 50 % eran inmigrantes y en el 50 % se confirmó contacto con adulto enfermo. Se aisló M. tuberculosis en jugo gástrico (4) y biopsia sinovial (1). En 3 pacientes no se consiguió aislamiento, pero se confirmó contacto con TB-MDR. Dos cepas presentaron resistencia a isoniazida (H) y rifampicina (R), cuatro a H, R y estreptomicina (S), una a H, R, S y pirazinamida (Z) y una a 11 fármacos. Seis pacientes recibieron tratamiento convencional inicial sin presentar mejoría. Una vez conocida la sensibilidad de la cepa, se administró tratamiento durante una media de 15 meses (rango: 12-18 meses) con 3-5 fármacos efectivos. Los efectos secundarios observados fueron: aumento de creatinfosfocinasa (1), tendinitis (1), alteración de potenciales visuales (1) y psicosis transitoria (1). Un paciente requirió lobectomía. Todos los pacientes evolucionaron satisfactoriamente. Conclusiones La TB-MDR debe sospecharse en casos con mala evolución, especialmente si proceden de zonas con altas tasas de resistencia. En niños enfermos con cultivos negativos y expuestos a TB-MDR, el tratamiento se realizará según el estudio de resistencias del caso índice. La resistencia limita las opciones terapéuticas y conlleva la utilización de fármacos con posibles efectos tóxicos

Aims To study the clinical and epidemiological features in eight pediatric patients with multidrug-resistant tuberculosis (MDR-TB) diagnosed from 1994 to 2005 in three hospitals in Madrid (Spain). Methods A retrospective study was performed in patients aged less than 15 years old with positive culture for multidrugresistant Mycobacterium tuberculosis and patients with negative cultures diagnosed after contact with MDR-TB. Results Pulmonary tuberculosis was diagnosed in seven patients and arthritis in one. Fifty percent of the patients were immigrants and an adult source case was found in four (50 %). M. tuberculosis was isolated in gastric juice in four patients and in synovial biopsy in one. In three patients cultures were negative but these patients had previously been in contact with MDR-TB. Two strains were resistant to isoniazid and rifampicin, four were resistant to isoniazid, rifampicin and streptomycin, one was resistant to isoniazid, rifampicin, streptomycin and pyrazinamide, and one was resistant to 11 drugs. Six patients initially received conventional treatment without improvement. Patients received therapy for 15 months (range: 12 to 18) with 3 to 5 drugs according to the sensitivity study. The following adverse effects were observed: creatine phosphokinase increase (one patient), tendinitis (one patient), alteration of visual evoked responses (one patient) and transitory psychosis (one patient). One patient required pulmonary lobectomy. All patients responded satisfactorily to medical treatment. Conclusions MDR-TB should be suspected in patients not responding to TB treatment, especially those from countries with high resistance rates. In patients with negative cultures, treatment should rely on the results of a sensitivity study in the adult source case. MDR-TB requires the use of second- line anti-TB drugs for prolonged periods with possible toxic effects