RESUMEN
INTRODUCTION AND OBJECTIVE: Fascia Manipulation® is one of the methods focusing on the deep fascia. The assumption is that fascial manipulation is carried out on precisely determined points - coordination centres (cc), and on a limited area so as the friction occurring during manipulation would cause a local rise in temperature due to the inflammatory reaction. Rise in temperature influences modification in consistency of elementary matter in the manipulated area, and by the same token causing a decrease in the negative effects of fascia densification which stems from accumulation of hyaluronic acid. The purpose of the research is to prove the thesis that fascial manipulation causes local rise in temperature due to inflammatory reaction. MATERIAL AND METHODS: For the research, 25 individuals with densification in lower limb area were qualified. They were exposed to a single, 3-minute facial manipulation®. By means of a thermal-imaging camera, changes in the temperature of the body in the examined area were evaluated. The body's temperature evaluation was carried out 8 times: before the treatment, 5 minutes after the treatment, and, next, 6, 12, 18, 24, 36, 48 hours after the treatment. RESULTS: The average surface temperature of the treated area before mobilization was 33.4°C. A statistically relevant increase in temperature was already observed 5 minutes after the treatment (increase of 0.5°C; p<0.001). However, the highest temperature was observed 24 hours after mobilization (increase of 2.4°C). The difference between the first and 7 other measurements was statistically relevant (p<0.001). CONCLUSIONS: The statistically relevant increase in temperature under the influence of fascial manipulation® in the treatment area can confirm the occurrence of inflammatory reaction.
Asunto(s)
Enfermedades del Tejido Conjuntivo/terapia , Fascia/fisiopatología , Manipulaciones Musculoesqueléticas , Adulto , Temperatura Corporal , Enfermedades del Tejido Conjuntivo/inmunología , Enfermedades del Tejido Conjuntivo/fisiopatología , Fascia/inmunología , Femenino , Humanos , Masculino , Termografía , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: Influenza vaccine is recommended for patients with autoimmune inflammatory rheumatic diseases who receive biological therapy. To evaluate if biological therapy impairs immunization after seasonal influenza vaccine. MATERIAL AND METHODS: Patients with inflammatory arthopathies, psoriasis, inflammatory bowel disease or connective tissue diseases who were receiving or were going to initiate biological therapy were included and vaccinated during 2014-2015 influenza season. ELISA was used to measure influenza antigen A and B antibodies, before and after vaccination. Demographic parameters, diagnosis and kind of treatment were recorded and their influence on the final serological status against influenza was studied. RESULTS: 253 subjects were analyzed. After vaccination, 77% of participants presented detectable antibodies against antigen A and 50.6% of them had detectable antibodies against antigen B. Final seropositivity rate against antigen B antibodies increased from baseline (50.6% vs 43.5%, p<0.001). Anti-TNF drugs were associated with better response and rituximab with the worst (79.2% vs 55.0% for final seropositivity against antigen A, p=0.020). Vaccine response in the rituximab group tended to improve when the interval between the drug administration and the vaccination was at least 12 weeks (seropositivity rate 80.0% in those with the longer interval vs 25.0% in the other group, p=0.054). CONCLUSIONS: Among the patients on biological therapy vaccinated against influenza, anti-TNF therapy was identified as a predictive factor of final seropositivity. Rituximab presented a lower rate of final seropositivity, which could be increased with an accurate administration schedule.
Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Antivirales/sangre , Terapia Biológica/efectos adversos , Virus de la Influenza A/inmunología , Virus de la Influenza B/inmunología , Vacunas contra la Influenza/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/inmunología , Biomarcadores/sangre , Enfermedades del Tejido Conjuntivo/tratamiento farmacológico , Enfermedades del Tejido Conjuntivo/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/inmunología , Masculino , Persona de Mediana Edad , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/inmunologíaRESUMEN
RATIONALE: Anti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) are a group of myositis-specific autoantibodies that are detected in the sera of patients with polymyositis and dermatomyositis (PM/DM) and also in those of patients with idiopathic interstitial pneumonias without any connective tissue disease (CTD), including PM/DM. Although we reported the clinical characteristics of interstitial lung disease with anti-ARS antibodies (ARS-ILD) with and without PM/DM, the long-term prognosis of ARS-ILD remains undetermined. As our previous studies revealed that ARS-ILD without PM/DM was similar to CTD-associated ILD, and that ARS-ILD with PM/DM was radiologically suggestive of a nonspecific interstitial pneumonia (NSIP) pathological pattern, we hypothesized that the prognosis of ARS-ILD might be distinct from that of idiopathic pulmonary fibrosis (IPF) without anti-ARS. OBJECTIVES: To elucidate the long-term outcome of ARS-ILD with and without PM/DM and compare it to that of IPF. METHODS: A two-center retrospective study was conducted. The study population comprised 36 patients with ARS-ILD (8 with PM, 12 with DM, and 16 without myositis throughout the course), 100 patients with IPF without anti-ARS, and 7 patients with NSIP without anti-ARS. The presence of anti-ARS was determined by RNA immunoprecipitation using the sera obtained at the time of diagnosis before specific treatment. MEASUREMENTS AND MAIN RESULTS: During the observational period (median 49 months; range, 1-114 months), 7 patients with ARS-ILD (19%; 3 with PM, 1 with DM, and 3 without PM/DM) and 51 patients with IPF (51%) died. Patients with ARS-ILD had better overall survival than those with IPF (log-rank test, P < 0.001) and similar survival compared to those with NSIP (log-rank test, P = 0.59). The prognosis for patients with ARS-ILD was similar between those with and without myositis (log-rank test, P = 0.91). At the median follow-up time of 76.5 months, 14 of the 36 patients with ARS-ILD had deteriorated. Both a decline in forced vital capacity or an initiation of long-term oxygen therapy during the course (odds ratio [OR], 5.34) and acute exacerbation (OR, 28.4) significantly increased the mortality risk. CONCLUSIONS: The long-term outcome of ARS-ILD was significantly better than that of IPF regardless of the presence or absence of myositis.
Asunto(s)
Aminoacil-ARNt Sintetasas/inmunología , Autoanticuerpos/sangre , Dermatomiositis/complicaciones , Fibrosis Pulmonar Idiopática/inmunología , Enfermedades Pulmonares Intersticiales/inmunología , Miositis/inmunología , Adulto , Anciano , Autoanticuerpos/inmunología , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/diagnóstico , Enfermedades del Tejido Conjuntivo/inmunología , Enfermedades del Tejido Conjuntivo/mortalidad , Dermatomiositis/inmunología , Dermatomiositis/mortalidad , Femenino , Humanos , Oxigenoterapia Hiperbárica/métodos , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/mortalidad , Masculino , Persona de Mediana Edad , Mortalidad , Miositis/mortalidad , Estudios Observacionales como Asunto , Evaluación de Resultado en la Atención de Salud , Pronóstico , ARN/inmunología , Estudios Retrospectivos , Análisis de Supervivencia , Capacidad Vital/fisiologíaRESUMEN
Biologic therapy continues to revolutionize the treatment of autoimmune disease, especially in rheumatology as the pathophysiology of both inflammation and autoimmune disease becomes better understood. These therapies are designed to dampen the response of the inflammatory cascades. Although the first biologic therapies were approved many years ago, expanding indications and new agents continue to challenge the traditional treatment strategies for rheumatic diseases. This article reviews the data supporting the current use of biologic therapies, including off-label indications, in a subset of rheumatic diseases including rheumatoid arthritis, lupus, inflammatory myositis, ankylosing spondylitis, psoriatic arthritis, vasculitis, and gout.
Asunto(s)
Enfermedades Autoinmunes/terapia , Terapia Biológica , Enfermedades del Tejido Conjuntivo/terapia , Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Psoriásica/inmunología , Artritis Psoriásica/terapia , Artritis Reumatoide/inmunología , Artritis Reumatoide/terapia , Enfermedades Autoinmunes/inmunología , Productos Biológicos/uso terapéutico , Terapia Biológica/métodos , Enfermedades del Tejido Conjuntivo/inmunología , Gota/terapia , Humanos , Factores Inmunológicos/uso terapéutico , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/terapia , Espondilitis Anquilosante/inmunología , Espondilitis Anquilosante/terapia , Resultado del Tratamiento , Vasculitis/inmunología , Vasculitis/terapiaRESUMEN
Breast prostheses have been criticized for being responsible for triggering systemic autoimmune disease. The presence of breast implants causes a natural foreign body reaction characterized by the infiltration of macrophages and T-cells. Using PubMed, Medline and eMedicine, we performed a systematic literature review on the stages of periprosthetic capsule formation and cells involved in order to understand which immunological pathways could be responsible for giving rise to, and the development of, connective tissue disease such as systemic sclerosis. We focused on the relationship between tissue growth factor-ß, interleukin (IL)-1, IL-6 and T helper 17 or T regulatory cells, as well as on their effects on the different steps of capsular tissue formation. A disturbance in the modulation of these key cytokines may be responsible, in susceptible individuals, for a perpetuation of the inflammatory reaction which can locally lead to capsular contracture and at the systemic level may contribute to triggering autoimmune diseases.
Asunto(s)
Adyuvantes Inmunológicos/efectos adversos , Enfermedades Autoinmunes/inmunología , Implantes de Mama/efectos adversos , Enfermedades del Tejido Conjuntivo/inmunología , Reacción a Cuerpo Extraño/inmunología , Inflamación/inmunología , Siliconas/efectos adversos , Animales , Enfermedades Autoinmunes/etiología , Enfermedades del Tejido Conjuntivo/etiología , Reacción a Cuerpo Extraño/etiología , Humanos , Inflamación/etiología , Interleucina-1/metabolismo , Interleucina-6/metabolismo , SíndromeRESUMEN
Vitamin D deficiency may contribute to pathological changes in the number and function of CD4+ T helper cell subsets (CD4+Th1, CD4+Th17, CD4+CD25(bright)Foxp3-natural regulatory T cells-nTreg) in patients with undifferentiated connective tissue disease (UCTD). The aim of the present study was to evaluate, whether alfacalcidol could restore immune-regulatory changes in patients with UCTD. We assessed the optimal dose of alfacalcidol that could normalize the elevated levels of IFN-γ expressed by the CD4+Th1 cells and the IL-17 expressed by Th17 cells. Furthermore alfacalcidol decreased the Th1 and Th17 related cytokine levels, repaired the nTreg/Th7 balance, and restored the functional activity of nTreg cells. Twenty one UCTD patients with Vitamin D deficiency (<30 ng/ml) were administered with three different daily doses of alfacalcidol. Seven patients were supplemented with 0.5 µg/day, 7 patients with 1.0 µg/day, and 7 patients with 1.5 µg/day alfacalcidol treatment during 5 weeks. Our results indicated that 1.0 µg/day alfacalcidol during 5 weeks was the optimal therapeutic regime to increase the vitamin D levels, repair the nTreg/Th17 balance and raise the capacity of nTreg cells to suppress the proliferation of autologous CD4+CD25- cells. 1.5 µg daily dose alfacalcidol was not more effective than the 1.0 µg/day treatment. In this study we described that vitamin D deficiency can contribute to the complex immune-regulatory abnormalities in patients with UCTD and vitamin D substitution therapy can improve the fine balance of pro- and anti-inflammatory processes in the disease.
Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Enfermedades del Tejido Conjuntivo/tratamiento farmacológico , Hidroxicolecalciferoles/administración & dosificación , Enfermedades del Sistema Inmune/tratamiento farmacológico , Interferón gamma/inmunología , Interleucina-17/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Deficiencia de Vitamina D/tratamiento farmacológico , Preescolar , Enfermedades del Tejido Conjuntivo/sangre , Enfermedades del Tejido Conjuntivo/inmunología , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta Inmunológica , Femenino , Humanos , Enfermedades del Sistema Inmune/sangre , Enfermedades del Sistema Inmune/inmunología , Lactante , Interferón gamma/sangre , Interleucina-17/sangre , Masculino , Linfocitos T Colaboradores-Inductores/metabolismo , Factores de Tiempo , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/inmunologíaRESUMEN
OBJECTIVE: The aim of this study was to perform a quantitative and functional analysis of natural CD4+CD25(high)Foxp3+ regulatory T cells (nTregs) and CD4+IL-17+ T cells, and to assess the serum levels of proinflammatory cytokines in patients with undifferentiated connective tissue disease (UCTD) before and after 5 weeks of 0.5 µg/day alfacalcidol supplementation. METHODS: Twenty-five patients with UCTD were enrolled in an open-label trial of alfacalcidol. Plasma levels of 25-hydroxyvitamin D [25(OH)D] were assessed by a high-performance liquid chromatography (HPLC) method. Flow cytometry was used for the quantification of nTregs and the IL-17 expression of T-helper (Th)17 cells. The serum concentrations of cytokines interleukin (IL)-12, interferon (IFN)-γ, IL-23, IL-17, IL-6, and IL-10 were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Treatment with alfacalcidol raised 25(OH)D levels from a mean of 23.5 ± 5.6 to 34.5 ± 7.4 ng/mL (p = 0.059; NS). Alfacalcidol treatment decreased both Th1- (IL-12 and IFN-γ) and Th17-related (IL-23, IL-17, IL-6) cytokine levels in UCTD patients, while the soluble IL-10 level increased (IL-12: 156.7 ± 75.2 vs. 87.5 ± 42.1 pg/mL, p < 0.001; IFN-γ: 41.5 ± 12.0 vs. 21.7 ± 9.9 pg/mL, p < 0.001; IL-23: 385.2 ± 82.2 vs. 210.0 ± 69.3 pg/mL, p < 0.001; IL-17: 37.8 ± 9.6 vs. 17.8 ± 4.5 pg/mL, p = 0.009; IL-6: 39.4 ± 11.3 vs. 23.5 ± 6.3 pg/mL, p < 0.001, IL-10: 8.4 ± 3.0 vs. 21.4 ± 9.7 pg/mL, p < 0.001). Alfacalcidol improved the Th17/nTreg imbalance, as it inhibited the IL-17 expression of Th17 cells, and increased the number of nTregs. The alfacalcidol might increase the capacity of nTreg cells to suppress the proliferation of autologous CD4+CD25â» cells. CONCLUSION: Our findings support the idea that vitamin D influences the Th17/nTreg imbalance in vitamin D-insufficient patients with UCTD and could be beneficial in the management of the disease.
Asunto(s)
Conservadores de la Densidad Ósea/efectos adversos , Enfermedades del Tejido Conjuntivo/inmunología , Homeostasis/efectos de los fármacos , Hidroxicolecalciferoles/efectos adversos , Linfocitos T Reguladores/efectos de los fármacos , Células Th17/efectos de los fármacos , Deficiencia de Vitamina D/inmunología , Adulto , Autoanticuerpos/sangre , Conservadores de la Densidad Ósea/uso terapéutico , Citocinas/sangre , Citocinas/metabolismo , Femenino , Factores de Transcripción Forkhead/sangre , Factores de Transcripción Forkhead/metabolismo , Homeostasis/inmunología , Humanos , Hidroxicolecalciferoles/uso terapéutico , Interleucina-17/sangre , Interleucina-17/metabolismo , Persona de Mediana Edad , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Vitamina D/sangre , Vitamina D/metabolismo , Deficiencia de Vitamina D/tratamiento farmacológico , Adulto JovenRESUMEN
A previous study of electrocardiography at rest showed that anti-Ro/SSA-positive patients with connective tissue disease (CTD) frequently had corrected QT (QTc) interval prolongation. Because QTc interval prolongation is a definite risk factor for arrhythmic sudden death in the general population, a 24-hour electrocardiographic monitoring study was performed to investigate the possible relation between QTc interval prolongation and incidence of ventricular arrhythmias as a possible expression of immunomediated electric instability of the myocardium in anti-Ro/SSA-positive patients with CTD. The study population consisted of 46 patients with CTD; 26 anti-Ro/SSA-positive and 20 anti-Ro/SSA-negative (control group) patients (Sjögren's syndrome, 9 and 3 patients; systemic lupus erythematosus, 4 and 9 patients; systemic sclerosis, 2 and 4 patients; undifferentiated CTD, 8 and 1 patients; mixed CTD, 2 and 2 patients, and polymyositis/dermatomyositis, 1 and 1 patient, respectively). All patients underwent ambulatory Holter electrocardiography to obtain 24-hour monitoring of the QTc interval and ventricular arrhythmias. With respect to the control group, anti-Ro/SSA-positive patients with CTD (1) commonly showed QTc interval prolongation (46% vs 5%), and this abnormality, when present, persisted for the 24 hours (global mean 24-hour QTc interval 440.5+/-23.4 vs 418.2+/-13.2 ms); (2) had a higher incidence of complex ventricular arrhythmias (i.e., Lown classes 2 to 5, 50% vs 10%) also in the absence of detectable cardiac abnormalities; and (3) in patients with CTD, there is a direct relation between global mean 24-hour QTc interval and ventricular arrhythmic load independently of age and disease duration. In conclusion, anti-Ro/SSA-positive patients with CTD seemed to have a particularly high risk of developing ventricular arrhythmias. The risk appeared related mainly to abnormalities in ventricular electrophysiologic characteristics emerging in the clinical setting as QTc interval prolongation.
Asunto(s)
Anticuerpos Antinucleares/sangre , Arritmias Cardíacas/epidemiología , Enfermedades del Tejido Conjuntivo/epidemiología , Adulto , Enfermedades del Tejido Conjuntivo/inmunología , Electrocardiografía Ambulatoria , Técnicas Electrofisiológicas Cardíacas , Femenino , Sistema de Conducción Cardíaco/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Miocardio/inmunología , Estudios SeroepidemiológicosAsunto(s)
Enfermedades del Tejido Conjuntivo/diagnóstico , Enfermedades del Sistema Nervioso/diagnóstico , Trastornos Neurocognitivos/diagnóstico , Vasculitis/diagnóstico , Autoanticuerpos/sangre , Enfermedades del Tejido Conjuntivo/inmunología , Humanos , Inmunidad Celular/inmunología , Enfermedades del Sistema Nervioso/inmunología , Trastornos Neurocognitivos/inmunología , Psiconeuroinmunología , Vasculitis/inmunologíaRESUMEN
OBJECTIVE: To investigate the prevalence of the 16/6 idiotype (16/6 Id), a major cross reactive idiotype of anti-DNA antibodies involved in the pathogenesis of experimental lupus, in subjects with an exogenous risk for the development of systemic lupus erythematosus (SLE). METHODS: The titer of 16/6 Id was determined by ELISA in sera of uranium miners exposed to heavy quartz dust: 15 developed definite and 12 probable SLE, 34 had clinical symptoms, and 27 had only serological signs (medium to high titer anti-dsDNA antibodies) of possible connective tissue disease (CTD) development. RESULTS: The prevalence of 16/6 Id was higher in all groups compared to healthy blood donors. It was 18.5% in miners with SLE (definite and probable) and 22.2-26.5% in miners with clinical and/or serological signs for developing CTD. All 16/6 Id positive miners were positive for anti-dsDNA antibodies and other autoantibodies associated with CTD. The prevalence of 16/6 Id in anti-dsDNA positive miners correlated slightly with CTD/SLE symptoms: 55.6% in patients with SLE, 47.4% in miners with possible CTD/SLE, and 22.2% in miners without CTD symptoms. Further, at short term followup, disease progressed in 2 miners of the 16/6 Id positive, but not in 16/6 Id negative miners. CONCLUSION: The detection of 16/6 Id in miners exposed to quartz dust may indicate a higher risk for development of SLE, warranting further studies of the role of 16/6 Id in the development of SLE in a cohort with the same sex, ethnicity, geographic region, and occupation.
Asunto(s)
Anticuerpos Antinucleares/sangre , Lupus Eritematoso Sistémico/inmunología , Minería , Cuarzo/efectos adversos , Uranio/efectos adversos , Anciano , Enfermedades del Tejido Conjuntivo/inmunología , Polvo/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/inducido químicamenteRESUMEN
Human adjuvant disease is the label given to a syndrome that resembles a connective tissue disease such as scleroderma and that has been hypothesized to follow augmentation mammoplasty with silicone gel implants or silicone with adulerants. To date, there is no proof that pure silicone is the cause of these symptoms. The cases presented in the literature suggest a comparison to the events seen in the rat adjuvant arthritis model. Male Lew/SsN rats (n = 65) were used. To evaluate both the adjuvant and antigenic properties of the gel implant, variations of the standard Freund's complete adjuvant inoculum were prepared. Tested were the abilities of low molecular weight silicone to act as an adjuvant and for fumed silica to act as an antigen by modifying a rat adjuvant arthritis model to include silicone and fumed silica. On day 0, 0.25 ml of each inoculum was injected intradermally into the plantar aspect of the hindfoot of each rat. The foot diameter was recorded at each time period, compared with the contralateral hindfoot, and normalized to controls at regular time periods over the course of 120 days. Silicone oil did not act as an adjuvant. Furthermore, fumed silica alone did not act as an antigen; however, it is capable of eliciting a reaction that is both delayed and uncharacteristic of the rat adjuvant arthritis model. These results indicate that "human adjuvant disease" may be inappropriate and misleading.
Asunto(s)
Adyuvantes Inmunológicos , Artritis Experimental/etiología , Dióxido de Silicio/efectos adversos , Aceites de Silicona/efectos adversos , Animales , Antígenos , Artritis Experimental/patología , Enfermedades Autoinmunes/etiología , Implantes de Mama , Enfermedades del Tejido Conjuntivo/etiología , Enfermedades del Tejido Conjuntivo/inmunología , Pie , Adyuvante de Freund/inmunología , Masculino , Mycobacterium/inmunología , Ratas , Ratas Endogámicas Lew , Dióxido de Silicio/inmunología , Aceites de Silicona/inmunologíaRESUMEN
Since first reported in 1982, published anecdotal reports have appeared with increasing frequency of patients in whom autoimmune connective tissue diseases developed after mammary augmentation with silicone gel-filled elastomer envelope-type prostheses. Although scleroderma has been reported most often, other diagnoses have included systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, and mixed connective tissue disease. Other patients have ill-defined connective tissue-like illnesses often referred to as "human adjuvant disease." The occurrence of dermatomyositis and polymyositis after silicone breast implants appears to be infrequent. We report two new cases of dermatomyositis after silicone exposure. In addition, a comprehensive review of the literature pertaining to rheumatic disease and silicone gel augmentation mammoplasty is presented to provide some perspective on this highly complicated and controversial subject.
Asunto(s)
Enfermedades Autoinmunes/etiología , Enfermedades del Tejido Conjuntivo/etiología , Enfermedades del Tejido Conjuntivo/inmunología , Dermatomiositis/etiología , Mamoplastia/efectos adversos , Prótesis e Implantes/efectos adversos , Siliconas/efectos adversos , Adulto , Animales , Femenino , Geles , Humanos , Persona de Mediana Edad , Enfermedades Reumáticas/etiología , Enfermedades Reumáticas/inmunología , Siliconas/químicaRESUMEN
OBJECTIVE: To study patients with side effects secondary to the injection of modelants. METHODS: We studied their clinical, serological, histopathological, radiographic, immunoregulatory and fibroblast culture features by standard methods. We studied thirty patients, 24 women, mean age: 38.2 years. Patients had received either mineral oil, guayacol, silicone or a mixture of these substances; some had received unknown material(s). RESULTS: The mean time between the injection and the onset of symptoms was six years (range: 0.1-24 years). All patients had sclerodermatous skin changes, subcutaneous nodules, edema and/or hyperpigmentation at the site(s) of injection(s); five individuals also had skin changes at sites remote from the injection. Thirteen patients had clinical features of an autoimmune disease. Eleven patients gave a history of arthralgias including four that had symmetrical non-erosive polyarthritis. Twenty of 28 patients (71%) had positive anti-nuclear antibodies. We found intracellular spontaneous production of IL-1 (interleukin-1) by patients' macrophages which was almost absent in normal cells (p < 0.001). Silica-stimulated monocytes from patients also secreted more IL-1 than those from normal subjects (p < 0.001) in autologous mixed lymphocyte reaction. Twelve patients had an early proliferative response. At day seven, a decreased proliferative response was seen in 12/19 patients (p < 0.001). Skin fibroblasts from 3/3 patients synthesized 3-to-5-fold more 3H-hyaluronic acid than normal control cells (p < 0.001). CONCLUSIONS: This report confirms the association between the injection of modelants and the development of autoimmune disease (human adjuvant disease, HAD). Our results implicate IL-1 in the amplification of the disease process. The similarities between primary scleroderma and human adjuvant disease now include immunological and connective tissue data. The study of these patients may help to understand the etiopathogenesis of some autoimmune diseases.
Asunto(s)
Enfermedades del Tejido Conjuntivo/inducido químicamente , Aceite Mineral/efectos adversos , Siliconas/efectos adversos , Piel/efectos de los fármacos , Adulto , Enfermedades Autoinmunes/inducido químicamente , Enfermedades del Tejido Conjuntivo/inmunología , Enfermedades del Tejido Conjuntivo/patología , Femenino , Fibroblastos/efectos de los fármacos , Humanos , Ácido Hialurónico/biosíntesis , Inmunofenotipificación , Inyecciones Subcutáneas , Interleucina-1/biosíntesis , Persona de Mediana Edad , Aceite Mineral/farmacología , Siliconas/farmacología , Piel/inmunología , Piel/patología , Cirugía PlásticaRESUMEN
Autoantibodies form under diverse circumstances. Some autoantibodies are clearly secondary phenomena in response to tissue injury. When there is defective microdebridement, tissue antigens will persist and will produce even more autoantibody. Scleroderma is classified as an autoimmune disease but autoantibodies are not always present. There is extensive literature on the early role of vascular changes and the presence of connective tissue active substances. There are clinical cases of scleroderma following implants of silicone, paraffin injections, and occupational silica or polyvinyl chloride exposure. It would be hard to describe a worse group of nondegradable substances capable of overloading the debridement system. It has been demonstrated that macrophages that ingest silica release factors that increase biosynthesis by fibroblasts. There may be many methods of arriving at the clinical pattern of scleroderma. Elimination of autoantibodies as a primary etiologic consideration will allow concentration on the other known physiologic factors. There is, in some cases, a secondary injury of the kidney from immune complexes. Autoimmunity, when it occurs, is a secondary phenomenon in scleroderma, or so-called 'human adjuvant disease'.
Asunto(s)
Autoinmunidad , Esclerodermia Sistémica/inmunología , Adyuvantes Inmunológicos , Autoanticuerpos/inmunología , Enfermedades del Tejido Conjuntivo/etiología , Enfermedades del Tejido Conjuntivo/inmunología , Humanos , Enfermedad Iatrogénica , Enfermedades Profesionales/inmunología , Esclerodermia Sistémica/etiologíaRESUMEN
Antinuclear antibodies (ANA) were studied in patients receiving PUVA therapy. Ten patients out of 124, (8%), considered for PUVA had ANA prior to therapy. During PUVA treatment ANA appeared in 34 out of 100 patients. Eight patients with ANA initially were treated and in 4 of them a significant increase in ANA titre was noted. A statistically significant difference was noted, when the first and last ANA tests for each patient were compared. No such difference was seen in a control group consisting of 33 patients. All PUVA patients generating ANA were evaluated clinically and with a laboratory screening. This evaluation was negative in all patients except one who developed ANA of the nucleolar staining pattern together with symptoms consistent with a collagen vascular disease. The ANA titres were generally low and the staining pattern was of the homogeneous type in all patients but one.
Asunto(s)
Anticuerpos Antinucleares/análisis , Terapia PUVA/efectos adversos , Fotoquimioterapia/efectos adversos , Psoriasis/tratamiento farmacológico , Enfermedades de la Piel/tratamiento farmacológico , Adolescente , Adulto , Anciano , Enfermedades del Tejido Conjuntivo/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/inmunología , Enfermedades de la Piel/inmunologíaRESUMEN
Antinuclear antibodies with a nucleolar staining pattern appeared in a psoriasis patient during PUVA therapy. No antinuclear antibodies were found after the termination of PUVA but they reappeared one year later together with symptoms consistent with a connective tissue disease. The course was fatal and the clinical and the laboratory investigations suggested a scleroderma-like syndrome.
Asunto(s)
Anticuerpos Antinucleares/análisis , Enfermedades del Tejido Conjuntivo/etiología , Terapia PUVA/efectos adversos , Fotoquimioterapia/efectos adversos , Psoriasis/tratamiento farmacológico , Enfermedades del Tejido Conjuntivo/inmunología , Femenino , Humanos , Persona de Mediana Edad , Psoriasis/inmunología , Esclerodermia Sistémica/etiologíaRESUMEN
The effect of D. Penicillamine (DP) at the dose of 50 mg/kg/day, on an immune induced connective tissue disease in rabbit, is compared to that of dexamethasone (Dexa) at the doses of 0.15 and 0.075 mg/kg/day. This model includes polyarthritis and lesions of connective tissue of liver, kidneys and lungs. The result of immunization is initially a non-specific macrophage infiltration and secondarily a specific lymphocyte and plasma-cell infiltration. In short treatment, high dose of Dexa inhibits the non-specific and specific responses while DP modifies only non specific response. In long treatment, Dexa at low dose and DP inhibit the two responses. Data suggest that, in vivo, macrophages is the target cell of DP.