RESUMEN
PURPOSE: To investigate the outcome of intravitreal ranibizumab and/or dexamethasone implant treatment for treatment of macular edema (ME) secondary to central or branch retinal vein occlusion (CRVO or BRVO) in a clinical setting. METHODS: Retrospective analysis of consecutive patients followed for at least 6 months. Data recorded included the type of occlusion, initial and final visual acuity, and number of injections. RESULTS: Sixty-five patients were included, 26 had CRVO and 39 BRVO. Mean (± SD) follow-up duration was 16 (± 7.7) months. Twenty-four (36.9%) patients received ranibizumab in monotherapy, 19 patients (29.3%) dexamethasone in monotherapy, and 22 patients (33.8%) received successively both treatments. In dexamethasone-treated patients, mean (± SD) visual acuity gain was 5.8 ± 10.7 letters for BRVO and 16.8 ± 15.6 letters for CRVO. In ranibizumab-treated patients, mean (± SD) visual acuity gain was 9.2 ± 10 letters for BRVO and 18.2 ± 20.5 letters for CRVO. CONCLUSION: Both intravitreal ranibizumab and dexamethasone intravitreal implant could be used as first-line therapy for patients with ME secondary to retinal vein occlusion.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Edema Macular/tratamiento farmacológico , Oclusión de la Vena Retiniana/complicaciones , Anciano , Inhibidores de la Angiogénesis , Dexametasona/administración & dosificación , Implantes de Medicamentos , Femenino , Estudios de Seguimiento , Glucocorticoides/administración & dosificación , Humanos , Inyecciones Intravítreas , Edema Macular/diagnóstico , Edema Macular/etiología , Masculino , Ranibizumab , Oclusión de la Vena Retiniana/diagnóstico , Estudios Retrospectivos , Factores de Tiempo , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Agudeza Visual , Cuerpo VítreoRESUMEN
BACKGROUND: Infectious events have been reported as major environmental triggers of thrombotic thrombocytopenic purpura (TTP). We detail here the potential association between infections and TTP. STUDY DESIGN AND METHODS: We recruited randomly and prospectively a cohort of 280 consecutive TTP patients during a 9-year period. Features of infection were systematically recorded. RESULTS: Features consistent with an infectious event were observed in 114 patients (41%) at time of TTP diagnosis. Infectious agents were documented in 34 cases and were mainly Gram-negative bacilli. At time of diagnosis infected patients more frequently had fever (p < 0.001). Infections at diagnosis did not impact prognosis and outcome. Thirty-six percent of patients experienced an infectious event during hospitalization, which resulted in more exacerbation of TTP (p = 0.02). Infections were not overrepresented during treatment in patients who received steroids and/or rituximab. Further genetic analysis of toll-like receptor (TLR)-9 functionally relevant polymorphisms revealed that TLR-9 +2848 G and TLR-9 +1174 A genotypes were more frequent in TTP patients than in controls (p = 0.04 and p = 0.026, respectively) and more particularly in patients negative for the Class II human leukocyte antigen system susceptibility allele DRB1*11 (p = 0.001 and p = 0.002, respectively). Haplotypes estimation showed that 1174A-2848G haplotype was significantly more frequent in TTP (p = 0.004), suggesting a primary role for this haplotype variation in conferring a predisposition for acquired TTP. CONCLUSION: Infections should be considered as an aggravating factor during the course of TTP. Particular polymorphisms in TLR-9 gene may represent risk factors for TTP.
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Infecciones/complicaciones , Púrpura Trombocitopénica Trombótica/genética , Receptor Toll-Like 9/genética , Adulto , Femenino , Francia/epidemiología , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Prevalencia , Estudios Prospectivos , Púrpura Trombocitopénica Trombótica/etiología , Sistema de Registros , Factores de Riesgo , Microangiopatías Trombóticas/epidemiología , Microangiopatías Trombóticas/genéticaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Ciclofosfamida/administración & dosificación , Dexametasona/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Humanos , Terapia Recuperativa , Resultado del TratamientoRESUMEN
Polyclonal CD8(+)/CD57(+)T cell lymphocytosis can be observed in various conditions such as chronic viral infections, autoimmune cytopenias, connective tissue diseases, chronic graft-versus-host disease and primary or secondary immune deficiencies. This population results from the chronic stimulation of CD8(+)/CD28(+)/CD57(-)lymphocytes by exogenous (mostly infection-related), autologous or allogeneic antigens. Paralleling chronic antigen stimulation, these CD8(+) T cells acquire a poor capacity to proliferate in standard conditions in relation with the loss of CD28, whereas CD57 antigen becomes expressed at their surface. CD8(+)/CD57(+)T cells represent activated cytotoxic T lymphocytes at a terminal stage of their differentiation with evidence of immunological senescence, which have usually lost their cytotoxic properties to become "regulatory" T cells. Patients with a CD8(+)/CD57(+)T cell lymphocytes expansion can display features of organ infiltration, as well as chronic idiopathic neutropenia. The search of this population has therefore a diagnostic value in clinical practice. A CD8(+)/CD57(+)T cell lymphocytes expansion must be suggested in patients with an organomegaly or organ(s) infiltration, particularly in patients infected by the human immunodeficiency virus or in the setting of allogeneic hematopoietic stem cell transplantation, as well as in patients with a neutropenia of unexplained origin. The identification of a CD8(+)/CD57(+)T cell lymphocytes expansion also has therapeutical consequences since patients with an organ infiltration or a neutropenia may respond remarkably to immunomodulatory therapies. The search of a CD8(+)/CD57(+) T cell expansion thus represents a useful and still poorly known diagnostic tool which clinical interest deserves further evaluation.
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Antígenos CD57/inmunología , Linfocitos T CD8-positivos/inmunología , Humanos , Inmunidad , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: Acquired thrombotic thrombocytopenic purpura is still associated with a 10-20% death rate. It has still not been possible to clearly identify early prognostic factors of death. This study involved thrombotic thrombocytopenic purpura patients with acquired severe (<10% of normal activity) ADAMTS13 deficiency and aimed to identify prognostic factors associated with 30-day death. DESIGN AND METHODS: The study involved a prospective cohort of patients and was carried out between October 2000 and August 2010. A validation cohort of patients was set up from September 2010 to August 2011. Altogether, 281 (analysis cohort) and 66 (validation cohort) consecutive adult thrombotic thrombocytopenic purpura patients with acquired severe ADAMTS13 deficiency were enrolled. The study evaluated 30-day mortality after treatment initiation according to characteristics at inclusion. RESULTS: Non-survivors (11%) were older (P=10(-6)) and more frequently presented arterial hypertension (P=5.10(-4)) and ischemic heart disease (P=0.013). Prognosis was increasingly poor with age (P=0.004). On presentation, cerebral manifestations were more frequent in non-survivors (P=0.018) and serum creatinine level was higher (P=0.008). The most significant independent variables determining death were age, severe cerebral involvement and LDH level 10 N or over. A 3-level risk score for early death was defined and confirmed in the validation cohort using these variables, with higher values corresponding to increased risk of early death. CONCLUSIONS: A risk score for early death was defined in patients with thrombotic thrombocytopenic purpura and validated on an independent cohort. This score should help to stratify early treatment and identify patients with a worse prognosis.
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Proteínas ADAM/deficiencia , Modelos Estadísticos , Púrpura Trombocitopénica Idiopática/mortalidad , Proteína ADAMTS13 , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Púrpura Trombocitopénica Idiopática/etiología , Curva ROC , Sistema de Registros , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: The objective was to assess the efficacy and safety of splenectomy and cyclophosphamide as salvage therapies in severe thrombotic thrombocytopenic purpura (TTP). STUDY DESIGN AND METHODS: During a 10-year period, patients who did not improve with plasma exchanges, steroids, vincristine, and/or rituximab were considered for splenectomy or cyclophosphamide. Patients with a documented severe (<10% of normal value) acquired ADAMTS13 deficiency are reported here. RESULTS: Eighteen patients with a severe acquired ADAMTS13 deficiency required a salvage therapy. Thirteen patients had a splenectomy 19 (interquartile range [IQR], 10-51) days after TTP diagnosis. One patient died the day after splenectomy. The remaining patients improved platelets (PLTs) until Day 6, along with a rapid and major lactate dehydrogenase improvement. Six patients, however, subsequently experienced a transient worsening. Durable PLT count recovery in survivors was observed within 13 (IQR, 11.5-25.5) days. Postoperative complications included thromboembolic events (two cases) and infections (five cases). Five patients received pulses of cyclophosphamide 12 (IQR, 12-15) days after TTP diagnosis. All patients recovered PLTs 10 (IQR, 9-24) days after the first pulse and two experienced a transient worsening. Three patients experienced infections. Three relapses occurred 5 months, 2.5 years, and 4.5 years after splenectomy and one relapse occurred 3.5 years after cyclophosphamide. After a 2.5 (IQR, 0.75-6.2)-year follow-up, the overall survival was 94%. CONCLUSION: Cyclophosphamide and splenectomy provide comparable high remission rates in severe TTP with acceptable side effects and should be considered in the more severe patients who do not improve with other therapies.
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Ciclofosfamida/administración & dosificación , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Púrpura Trombocitopénica Trombótica/mortalidad , Terapia Recuperativa/métodos , Esplenectomía/métodos , Adulto , Ciclofosfamida/efectos adversos , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Masculino , Agonistas Mieloablativos/administración & dosificación , Agonistas Mieloablativos/efectos adversos , Quimioterapia por Pulso , Sistema de Registros/estadística & datos numéricos , Inducción de Remisión , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess the efficacy and safety of rituximab in adults responding poorly to standard treatment for severe autoimmune thrombotic thrombocytopenic purpura. DESIGN: Open-label prospective study. Outcomes in the survivors were compared to those of 53 historical survivors who were given therapeutic plasma exchange alone or with vincristine. SETTING: Hospitals belonging to the Reference Network for Thrombotic Microangiopathies in France. PATIENTS: Twenty-two adults with either no response or a disease exacerbation when treated with intensive therapeutic plasma exchange. INTERVENTION: Add-on rituximab therapy, four infusions over 15 days. MEASUREMENTS AND MAIN RESULTS: One patient died despite two rituximab infusions. In the rituximab-treated patients, the time to a durable remission was significantly shortened (p = .03), although the plasma volume required to achieve a durable remission was not significantly different compared to the controls. Platelet count recovery occurred within 35 days in all 21 survivors, compared to only 78% of the historical controls (p < .02). Of the rituximab-treated patients, none had a relapse within the first year but three relapsed later on. In patients treated with rituximab, a rapid and profound peripheral B-cell depletion was produced, lasting for 9 months and correlating with higher a disintegrin and metalloproteinase with thrombospondin-13 activity and lower anti-a disintegrin and metalloproteinase with thrombospondin-13 antibody titers. These differences were no longer significant after 12 months. No severe side effects occurred. CONCLUSIONS: Adults with severe thrombocytopenic purpura who responded poorly to therapeutic plasma exchange and who were treated with rituximab had shorter overall treatment duration and reduced 1-yr relapses than historical controls.
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Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Factores Inmunológicos/uso terapéutico , Intercambio Plasmático , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Adulto , Femenino , Humanos , Masculino , Rituximab , Terapia Recuperativa , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
Severe ADAMTS13 deficiency occurs in 13% to 75% of thrombotic microangiopathies (TMA). In this context, the early identification of a severe, antibody-mediated, ADAMTS13 deficiency may allow to start targeted therapies such as B-lymphocytes-depleting monoclonal antibodies. To date, assays exploring ADAMTS13 activity require skill and are limited to only some specialized reference laboratories, given the very low incidence of the disease. To identify clinical features which may allow to predict rapidly an acquired ADAMTS13 deficiency, we performed a cross-sectional analysis of our national registry from 2000 to 2007. The clinical presentation of 160 patients with TMA and acquired ADAMTS13 deficiency was compared with that of 54 patients with detectable ADAMTS13 activity. ADAMTS13 deficiency was associated with more relapses during treatment and with a good renal prognosis. Patients with acquired ADAMTS13 deficiency had platelet count < 30 x 10(9)/L (adjusted odds ratio [OR] 9.1, 95% confidence interval [CI] 3.4-24.2, P<.001), serum creatinine level < or =200 micromol/L (OR 23.4, 95% CI 8.8-62.5, P<.001), and detectable antinuclear antibodies (OR 2.8, 95% CI 1.0-8.0, P<.05). When at least 1 criteria was met, patients with a severe acquired ADAMTS13 deficiency were identified with positive predictive value of 85%, negative predictive value of 93.3%, sensitivity of 98.8%, and specificity of 48.1%. Our criteria should be useful to identify rapidly newly diagnosed patients with an acquired ADAMTS13 deficiency to better tailor treatment for different pathophysiological groups.
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Proteínas ADAM/deficiencia , Valor Predictivo de las Pruebas , Microangiopatías Trombóticas/diagnóstico , Proteínas ADAM/inmunología , Proteína ADAMTS13 , Adulto , Anciano , Anticuerpos , Anticuerpos Antinucleares/sangre , Creatinina/sangre , Estudios Transversales , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Sistema de Registros , Microangiopatías Trombóticas/complicaciones , Microangiopatías Trombóticas/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Specific cutaneous lesions of Waldenström macroglobulinemia are rare and include neoplastic cell infiltrates, IgM bullous disease, and so-called IgM-storage papules, which characterize cutaneous macroglobulinosis (CM). OBSERVATIONS: We report 2 patients with CM. In patient 1, CM started as small papules, as reported in most of the previously published case studies of CM. In patient 2, lesion evolution was remarkable by its severity, with large ulcerated nodules, and the disease progressed rapidly. As mentioned for half the previously described patients, peripheral neuropathy was suspected in patient 2 and demonstrated in patient 1, with production of antibodies to myelin-associated glycoprotein. CONCLUSIONS: To the best of our knowledge, rituximab treatment of Waldenström macroglobulinemia associated with CM has not been described previously. Rituximab caused complete remission of the lesions in patient 1, whereas disease rapidly progressed in patient 2, and the patient died. These observations suggest that evolution of the cutaneous IgM-storage lesions reflects that of the underlying Waldenström macroglobulinemia, and CM is not a prognostic marker.
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Enfermedades de la Piel/etiología , Enfermedades de la Piel/patología , Macroglobulinemia de Waldenström/patología , Anciano , Humanos , Masculino , Enfermedades de la Piel/terapia , Macroglobulinemia de Waldenström/complicaciones , Macroglobulinemia de Waldenström/terapiaRESUMEN
OBJECTIVE: To specify the clinical and biological characteristics of thrombotic microangiopathies (TMAs) associated with a recent diagnosis of cancer. PATIENTS AND Methods. Multicenter study involving 14 national centers. Cross-sectional analysis of 20 patients with cancer-associated TMAs included in our national registry from October 2000 to July 2007. Patients were also compared with 134 adult patients with an acquired idiopathic TMA by univariate analysis. RESULTS: Patients with a cancer-associated TMA typically displayed severe weight loss, dyspnea, bone pain, as well as disseminated intravascular coagulopathy and massive erythromyelemia (75%, 55%, 50%, 41%, and 85% of cases, respectively). By contrast, these features were observed with a much lower incidence in patients with an idiopathic TMA (8.9%, 19.7%, 0.8%, 7.1%, and 17.5%, respectively). Moreover, median platelet count was higher (48 x 10(9)/l; range, 21-73 x 10(9)/l versus 19 x 10(9)/l; range, 10-38 x 10(9)/l, respectively) and median serum creatinine level was lower (74 microM [range, 68-102] versus 113 microM [range, 80-225], respectively). The activity of the specific von Willebrand factor-cleaving proteinase ADAMTS13 was detectable in 14/17 studied patients. Platelet count improvement was observed in only seven patients and paralleled the response to chemotherapy. Prognosis of patients with cancer-associated TMAs was very poor, with a 30-day and 2-year mortality rate of 50% and 95%, respectively. CONCLUSION: Cancer-associated TMAs display specific features at onset that should prompt investigation of an underlying disseminated malignancy. In this context, chemotherapy rather than plasma is mandatory since TMA prognosis parallels that of cancer.
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Neoplasias/complicaciones , Microangiopatías Trombóticas/complicaciones , Proteínas ADAM/sangre , Proteína ADAMTS13 , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Estudios Prospectivos , Microangiopatías Trombóticas/sangre , Microangiopatías Trombóticas/enzimología , Resultado del Tratamiento , Factor de von Willebrand/metabolismoRESUMEN
In African tick bite fever (ATBF), inoculation eschar - resulting from disruption of the cutaneous barrier - may be a risk factor for cellulitis. We report 2 cases of ATBF associated with cellulitis. A 77-year-old woman was referred for severe leg cellulitis upon returning from sub-Saharan Africa. She developed erythematous macules. Rickettsia africae was detected by PCR assay from a skin biopsy specimen, and ATBF diagnosis was confirmed. A 75-year-old man was hospitalized after his return from Zimbabwe for a maculopapular exanthema and erysipelas-like rash of the leg. The diagnosis of cellulitis associated with ATBF was confirmed by PCR and serological methods. Both patients were treated for ATBF and cellulitis by a combination of doxycycline and beta-lactam antibiotics, and both had a good recovery. Inoculation eschar may be a risk factor for cellulitis; thus, we hypothesize a non-fortuitous association between ATBF and cellulitis.
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Celulitis (Flemón)/complicaciones , Celulitis (Flemón)/diagnóstico , Infecciones por Rickettsia/complicaciones , Infecciones por Rickettsia/diagnóstico , Enfermedades por Picaduras de Garrapatas/complicaciones , Enfermedades por Picaduras de Garrapatas/diagnóstico , Anciano , Animales , Antibacterianos/uso terapéutico , Celulitis (Flemón)/tratamiento farmacológico , Doxiciclina/uso terapéutico , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Rickettsia/aislamiento & purificación , Infecciones por Rickettsia/tratamiento farmacológico , Medición de Riesgo , Enfermedades por Picaduras de Garrapatas/tratamiento farmacológico , Viaje , Resultado del Tratamiento , Zimbabwe , beta-Lactamas/uso terapéuticoRESUMEN
Our aim was to evaluate remission and relapse rates and the number of laser sessions necessary for treatment. Among the relapses observed, we sought to differentiate between the persistence and recurrence of an HPV-induced lesion. This retrospective study was performed in patients, immunocompetent or not, treated with CO2 laser for condylomatous or neoplastic anogenital lesions by the same operator over a period of 12 months. 106 treated patients were followed for 6 months. Three groups of patients were analysed: HIV(+) patients, patients with therapeutic immunosuppression (ImST) and immunocompetent patients (ImC). Twenty-seven (25.5%) patients presented with high-grade intraepithelial neoplasms (IEN III). IEN III lesions were more common in the HIV(+) group than in immunocompetent patients (47.4% versus 20.2%, p = 0.015). The development of HPV-induced lesions at several sites on the body was also more common in HIV(+) patients. Post-laser controls at one month demonstrated a clinical absence of HPV-induced lesions in 81.2% of cases, recurrence in 12.6% of cases and persistence in 6.6% of cases. Remission rates at one month did not differ significantly between the three groups. 93% of patients in remission at one month were still in remission at three months. IEN III neoplasms in remission at one month remained so at six months. ImC and ImST patients presented more frequently with recurrence than persistence, when compared with HIV(+) patients. At six months, 83% of patients were in remission after 1.4 laser treatments. The excision of HPV-induced anogenital lesions using CO2 laser remains an efficient treatment, even if it needs to be repeated if lesions recur or persist. CO2 laser treatment under colposcopic guidance can achieve remission in both immunocompromised and non-compromised patients with longstanding lesions.
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Condiloma Acuminado/cirugía , Infecciones por VIH/complicaciones , Recurrencia Local de Neoplasia/cirugía , Papillomaviridae , Neoplasias Cutáneas/cirugía , Adolescente , Adulto , Anciano , Canal Anal/patología , Condiloma Acuminado/complicaciones , Condiloma Acuminado/epidemiología , Condiloma Acuminado/patología , Femenino , Francia/epidemiología , Humanos , Inmunocompetencia , Terapia por Láser , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Pene/patología , Perineo/patología , Estudios Retrospectivos , Escroto/patología , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/patología , Resultado del Tratamiento , Uretra/patología , Vulva/patologíaRESUMEN
Epidemiological aspects of syphilis in Western countries have undergone a significant change with respect to the number of cases. Detection of Treponema pallidum is difficult, and the correct diagnosis of secondary syphilis can be critical. In this study, biopsy samples from skin lesions of 12 patients with secondary syphilis were used. Diagnosis of syphilis was based on clinical presentation, dark-field microscope analysis, and serological tests. Using a polyclonal antibody directed against T. pallidum, we show the presence of T. pallidum in 90% of the samples studied with the bacteria located in the epidermis and the upper dermis. The T. pallidum 47-kDa surface protein gene could be amplified by PCR in 75% of the skin lesions. When combining both techniques, T. pallidum was detected in 92% of the samples from patients with secondary syphilis but not in the control samples. Our work suggests that both immunohistochemistry and PCR could be useful for the diagnosis of secondary syphilis and may be helpful in some rare cases when serological assays failed to detect T. pallidum antibodies.
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Inmunohistoquímica/métodos , Reacción en Cadena de la Polimerasa/métodos , Sífilis/diagnóstico , Treponema pallidum/genética , Treponema pallidum/inmunología , Adulto , Secuencia de Aminoácidos , Anticuerpos Antibacterianos/inmunología , Anticuerpos Antibacterianos/metabolismo , Secuencia de Bases , Biopsia , Proteínas Portadoras/análisis , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , ADN Bacteriano/genética , Femenino , Humanos , Lipoproteínas/análisis , Lipoproteínas/genética , Lipoproteínas/metabolismo , Masculino , Datos de Secuencia Molecular , Sensibilidad y Especificidad , Piel/metabolismo , Piel/microbiología , Piel/patología , Sífilis/genética , Sífilis/metabolismo , Sífilis/patología , Treponema pallidum/metabolismoRESUMEN
We report on scurvy in 3 liver transplant recipients. Clinical presentation was limited to ecchymotic purpura and mild follicular keratosis with no mucosal involvement. Skin biopsies suggest vitamin C deficiency, which was confirmed by a low level of vitamin C in both sera and leukocyte specimens. Skin lesions dramatically improved within a few weeks after supplementation with ascorbic acid.
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Trasplante de Hígado/efectos adversos , Escorbuto/etiología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escorbuto/patologíaRESUMEN
OBJECTIVE: To evaluate the efficiency of Coleman lipostructure in patients infected with human immunodeficiency virus (HIV). DESIGN: Open-label study and survey. SETTING: Ambulatory dermatosurgery department of a university hospital. PATIENTS: Thirty-three consecutive HIV-infected patients undergoing Coleman lipostructure between 2000 and 2001. INTERVENTIONS: Clinical examination, blood tests, and standardized photographs at baseline and 1 year after the lipostructure. MEAN OUTCOME MEASURES: Efficiency was assessed by the agreement of 3 independent medical specialists on facial lipodystrophy improvement after surgery and by patient satisfaction. RESULTS: Facial lipoatrophy was improved in 12 patients (36%; 95% confidence interval, 20%-52%) as judged by all 3 evaluators. Quantity of fat injected (P = .01) and a low serum triglyceride level before surgery (P = .03) were significantly associated with improvement of facial lipoatrophy. Of the 33 patients, 14 (43%) were very satisfied, 17 (50%) were partly satisfied, and 27 (81%) had a better quality of life. The most common comment was that the patient looked better and appeared less ill. CONCLUSION: Our 1-year evaluation of Coleman lipostructure for correction of facial lipoatrophy in HIV-infected patients proved the efficiency of this treatment when measured conservatively by agreement on improvement by 3 independent specialists and demonstrated a patient satisfaction rate of 93%.
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Tejido Adiposo/trasplante , Terapia Antirretroviral Altamente Activa/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Lipodistrofia/inducido químicamente , Lipodistrofia/cirugía , Adulto , Femenino , Humanos , Inyecciones Subcutáneas , Lipodistrofia/patología , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Trasplante Autólogo/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL). Patients with limited patch and/or plaque disease have a normal life expectancy. Neutrophilic dermatosis (ND) may be associated with various hematologic disorders. However, its association with CTCL is exceptional and has been reported only twice with leukemic forms of CTCL. OBSERVATIONS: Three patients with MF developed ND resistant to conventional therapies and responsible for an impaired quality of life due to constitutional symptoms and painful cutaneous lesions. All patients underwent an aggressive treatment course despite their varying initial clinical stages of MF, and all experienced a fatal outcome less than 18 months after the onset of ND. CONCLUSIONS: The association of MF with ND is exceptional and carries a poor prognosis, but the pathophysiologic nature of this association remains unclear. It may involve neutrophil chemoattractant cytokine production by tumor cells. A triggering role of interferon alfa is also possible.
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Micosis Fungoide/patología , Neoplasias Cutáneas/patología , Síndrome de Sweet/diagnóstico , Adulto , Anciano , Antineoplásicos/uso terapéutico , Biopsia con Aguja , Progresión de la Enfermedad , Resultado Fatal , Humanos , Inmunohistoquímica , Inmunosupresores/uso terapéutico , Linfoma Cutáneo de Células T , Masculino , Persona de Mediana Edad , Micosis Fungoide/complicaciones , Micosis Fungoide/tratamiento farmacológico , Estadificación de Neoplasias , Medición de Riesgo , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/tratamiento farmacológico , Síndrome de Sweet/complicaciones , Síndrome de Sweet/tratamiento farmacológicoRESUMEN
BACKGROUND: NRTI-induced host toxicity is proposed to involve cellular mitochondrial DNA (mtDNA) depletion. Determinants of cellular mtDNA copy number from HIV-infected patients receiving HAART and HIV-seronegative controls were investigated from subcutaneous fat samples, and relation with antiretroviral regimen was studied. STUDY DESIGN: HIV-infected patients receiving HAART (n = 50), HIV-infected patients not currently under HAART regimen (n = 2) and HIV-seronegative controls (n = 9) of similar age and BMI were enrolled prospectively when undergoing Coleman's lipostructure for correction of facial lipoatrophy or plastic surgery, respectively. After centrifugation, abdominal fat tissue was collected and stored at -80 degrees C. MtDNA analysis was blindly performed after a total DNA extraction from adipose tissue, followed by a real-time PCR quantification. The log of mtDNA copies/cell in adipose tissue [log(DNA)] was compared between groups by means of analysis of variance. RESULTS: The log(DNA) in adipose tissue of HIV-infected patients was significantly lower than in the HIV-seronegative control group (P < 0.0001). In HIV-infected patients, log(DNA) was significantly reduced in the 50 NRTI-treated patients (P < 0.01), but not when considering mtDNA level according to the use of PI or NNRTI in current HAART regimen. In NRTI-treated patients, only stavudine (n = 20) and didanosine (n=14) were significantly and independently associated with reduced mtDNA level (P < 0.0001 and <0.05, respectively). Currently stavudine or didanosine-treated patients had a significant reduced mtDNA level compared to past users (P < 0.0001 and <0.05, respectively). Other clinical, biological, and immuno-virological variables than NRTI did not correlate significantly to adipocyte mtDNA level. CONCLUSION: This study supports that current treatment by NRTI is a main determinant of mtDNA depletion in adipose tissue of HIV-seropositive patients with peripheral fat wasting. Stavudine or didanosine current intake is significantly associated with mtDNA depletion in vivo, that could be reversible after the discontinuation of these molecules, when considering mtDNA level according to current use versus past use of these molecules.