RESUMO
To examine clinical course of early systemic sclerosis (SSc) and identify factors for progression of acro-osteolysis by a retrospective cohort study. Dual time-point hand radiography was performed at median interval (range 3.0 ± 0.4 years) in 64 recruited patients. Progressive acro-osteolysis was defined as the worsening of severity of acro-osteolysis according to rating scale (normal, mild, moderate, and severe). Incidence of the progression was determined. Cox regression was analyzed for the predictors. A total of 193.6 per 100 person-years, 19/64 patients had progressive acro-osteolysis with incidence of 9.8 per 100-person-years (95% CI 6.3-15.4). The median time of progressive acro-osteolysis was 3.5 years. Rate of progression increased from 1st to 3rd years follow-up with the progression rate at 1-, 2- and 3-years were 0, 2.0 and 18.3%, respectively. Patients with positive anti-topoisomerase I tended to have more progressive acro-osteolysis but no significant predictors on Cox regression. 44%, 18%, and 33% of who had no, mild, and moderate acro-osteolysis previously developed progression and 10 turned to be severe acro-osteolysis. In conclusion, the incidence of progressive acro-osteolysis was uncommon in early SSc but the rate of progression was pronouncedly increasing after three years follow-up. A half of the patients progressed to severe acro-osteolysis.
Assuntos
Acro-Osteólise , Escleroderma Sistêmico , Humanos , Estudos Retrospectivos , Acro-Osteólise/diagnóstico por imagem , Acro-Osteólise/complicações , Escleroderma Sistêmico/diagnóstico por imagem , Escleroderma Sistêmico/complicações , Radiografia , Progressão da DoençaRESUMO
Importance: Degos-like lesions are cutaneous manifestations of a small-vessel vasculopathy that appear as atrophic, porcelain-white papules with red, telangiectatic borders. No study has adequately examined Degos-like lesions in patients with systemic sclerosis (SSc). Objective: To characterize the serologic, cutaneous, and internal organ manifestations associated with Degos-like lesions in a large cohort of patients with SSc. Design, Settings, and Participants: This retrospective cohort study involved adult patients with SSc who were seen at Stanford Rheumatologic Dermatology Clinic between January 1, 1998, and December 31, 2018. Participants fulfilled the 2013 classification criteria for SSc. Data analysis was conducted from February 1 to June 1, 2019. Main Outcomes and Measures: Data on demographic characteristics; autoantibody status; clinical characteristics, including cutaneous and systemic manifestations of SSc; and presence of Degos-like lesions were collected. Results: The cohort comprised 506 patients with SSc (447 females [88.3%]; mean [SD] age at first non-Raynaud disease symptoms, 46.1 [15.2] years). Twenty-seven patients (5.3%) had Degos-like lesions, of whom 24 (89.0%) had lesions affecting the fingers. Patients with Degos-like lesions were more likely to have diffuse cutaneous SSc compared with patients without lesions (15 [55.6%] vs 181 [37.8%]; P = .04). Degos-like lesions were also associated with acro-osteolysis (10 [37.0%] vs 62 [12.9%]; P < .01), digital ulcers (15 [55.6%] vs 173 [36.1%]; P = .04), and calcinosis (15 [55.6%] vs 115 [24.0%]; P < .01). While Degos-like lesions were not associated with internal organ manifestations, such as scleroderma renal crisis, interstitial lung disease, or pulmonary arterial hypertension, there was P < .10 for the association with gastric antral vascular ectasia. Conclusions and Relevance: Results of this study suggest an association of Degos-like lesions with diffuse cutaneous SSc and other cutaneous manifestations of vasculopathy, including acro-osteolysis, calcinosis, and digital ulcers. A prospective longitudinal study is warranted to examine the onset of Degos-like lesions and to elucidate whether these lesions play a role in SSc.
Assuntos
Acro-Osteólise , Calcinose , Escleroderma Sistêmico , Doenças Vasculares , Adulto , Feminino , Humanos , Adolescente , Estudos Longitudinais , Estudos Prospectivos , Estudos Retrospectivos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Acro-Osteólise/complicaçõesRESUMO
OBJECTIVE: To perform a scoping review focusing on osteolysis in systemic sclerosis (SSc). METHODS: This review was performed in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) recommendations. RESULTS: From a total of 351 results, 29 articles were included for the final analysis. The publications included proved to be heterogeneous regarding the population and inclusion criteria. The lack of a standardized method of detection of osteolysis further enhanced these inequalities. Most studies reported location/prevalence of osteolysis and associations with other manifestations, with only a minority focusing on topics like predictors of osteolysis and its prognostic value. None of the authors addressed treatment approach. The most frequently analyzed and prevalent location was acro-osteolysis (AO). Diffuse cutaneous subtype and anti-topoisomerase I antibody correlated positively with AO. Disease duration, calcinosis, and digital ischemia were the features more frequently associated with AO, but only the last 2 predicted AO. Ultrasound showed high sensitivity for detection of AO. CONCLUSION: Despite the effect that osteolysis has on patients with SSc, there is a significant lack of studies on this area. Notably, there are no studies that we know of focused on treatment. Also, there is a lack of longitudinal studies that would allow a reliable assessment of its prognostic value and predictors.
Assuntos
Acro-Osteólise , Osteólise , Escleroderma Sistêmico , Humanos , Acro-Osteólise/complicações , Osteólise/diagnóstico por imagem , Osteólise/etiologia , Escleroderma Sistêmico/complicações , PeleRESUMO
Werner syndrome (WS) is an autosomal recessive syndrome characterized by genomic instability that affects multiple body systems. The characteristic features of the disease include growth retardation, short stature, alopecia, scleroderma, atrophic skin with ulcerations, infertility, cataracts, premature arteriolosclerosis, diabetes, osteoporosis, and increased risk of malignancies. Werner syndrome protein (WRN) protein deficiency in this disease causes changes in gene expression, similar to those observed in normal aging. As the median age of death in WS is the fourth or fifth decade of life, early diagnosis leads to a better screening opportunity for malignancies. Herein, we present a 28-year-old woman who presented with growth arrest, dyspigmentation, and acroosteolysis and was later diagnosed with Werner syndrome.
Assuntos
Acro-Osteólise , Diabetes Mellitus , Osteoporose , Síndrome de Werner , Feminino , Humanos , Adulto , Síndrome de Werner/complicações , Síndrome de Werner/diagnóstico , Síndrome de Werner/genética , Acro-Osteólise/diagnóstico , Acro-Osteólise/complicações , Osteoporose/complicações , Osteoporose/diagnóstico , EnvelhecimentoAssuntos
Acro-Osteólise/diagnóstico por imagem , Artrite/diagnóstico por imagem , Articulação da Mão/diagnóstico por imagem , Esclerodermia Difusa/diagnóstico , Acro-Osteólise/complicações , Acro-Osteólise/diagnóstico , Adulto , Artrite/complicações , Artrite/diagnóstico , Artrite/tratamento farmacológico , Autoanticorpos/imunologia , Calcinose/complicações , Calcinose/diagnóstico por imagem , Contratura/complicações , Contratura/diagnóstico , Contratura/diagnóstico por imagem , DNA Topoisomerases Tipo I/imunologia , Humanos , Fatores Imunológicos/uso terapêutico , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Radiografia , Doença de Raynaud , Rituximab/uso terapêutico , Esclerodermia Difusa/complicações , Esclerodermia Difusa/tratamento farmacológico , Esclerodermia Difusa/imunologiaAssuntos
Acro-Osteólise/complicações , Dedos/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/complicações , Doença Mista do Tecido Conjuntivo/complicações , Acro-Osteólise/diagnóstico por imagem , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/diagnóstico por imagem , RadiografiaAssuntos
Acro-Osteólise/patologia , Diabetes Mellitus Tipo 1/patologia , Acro-Osteólise/complicações , Acro-Osteólise/diagnóstico por imagem , Diabetes Mellitus Tipo 1/complicações , Neuropatias Diabéticas/complicações , Neuropatias Diabéticas/patologia , Feminino , Falanges dos Dedos da Mão/diagnóstico por imagem , Falanges dos Dedos da Mão/patologia , Dedos/diagnóstico por imagem , Dedos/patologia , Humanos , Pessoa de Meia-Idade , RadiografiaRESUMO
OBJECTIVES: Acro-osteolysis (bony resorption of the terminal digital tufts) is a well-recognized, but under-researched, manifestation of SSc. Our aim was to investigate the hypothesis that acro-osteolysis is associated with (i) the severity of digital ischaemia and (ii) the presence of calcinosis. METHODS: This was a retrospective study of 101 patients with SSc in whom hand radiographs taken between 2001 and May 2008 were available for review. These radiographs were graded for severity of acro-osteolysis on a 0-4-point scale for each finger (0 = normal bone structure, 4 = severe pencilling of the terminal phalanges). From these scores, patients were subdivided into the following two groups: normal/minimal acro-osteolysis and moderate/severe acro-osteolysis. The presence or absence of calcinosis (mild, moderate or severe) was also documented. RESULTS: Of the 101 patients, 68 were grouped as normal/minimal acro-osteolysis and 33 as moderate/severe acro-osteolysis. Forty-five had severe digital ischaemia: 25 (76%) of the patients with moderate/severe acro-osteolysis compared with 20 (29%) of those with normal/minimal acro-osteolysis (multifactorial analysis: P < 0.001). Patients with moderate/severe acro-osteolysis were more likely to have severe calcinosis (33% vs 13%), but this was not statistically significant after adjustment for potential confounders. CONCLUSION: Acro-osteolysis was strongly associated with severe digital ischaemia. The potential association with severe calcinosis merits further study. Prospective studies are required to investigate acro-osteolysis as a marker of digital vascular disease progression and of treatment response.
Assuntos
Acro-Osteólise/complicações , Calcinose/complicações , Dedos/irrigação sanguínea , Isquemia/etiologia , Escleroderma Sistêmico/complicações , Acro-Osteólise/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Calcinose/diagnóstico por imagem , Feminino , Dedos/diagnóstico por imagem , Humanos , Isquemia/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Escleroderma Sistêmico/diagnóstico por imagem , Adulto JovemRESUMO
Hajdu-Cheney syndrome is a rare, autosomal dominant skeletal dysplasia marked by acro-osteolysis of the distal phalanges and severe osteoporosis. Although there are more than 60 reports published to date, proper treatment and subsequent outcome have been scarce. Herein, we report a progress of anti-resorptive therapy with zoledronic acid, in a woman with Hajdu-Cheney syndrome. Results suggest that anti-resorptive therapy may be important in delaying the progress of osteoporosis and preventing fractures, but not necessarily acro-osteolysis itself.
Assuntos
Acro-Osteólise/tratamento farmacológico , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Síndrome de Hajdu-Cheney/tratamento farmacológico , Imidazóis/uso terapêutico , Osteoporose/tratamento farmacológico , Acro-Osteólise/complicações , Adulto , Feminino , Síndrome de Hajdu-Cheney/complicações , Humanos , Osteoporose/complicações , Ácido ZoledrônicoRESUMO
Mutation in ZMPSTE24 gene, encoding a major metalloprotease, leads to defective prelamin A processing and causes type B mandibuloacral dysplasia, as well as the lethal neonatal restrictive dermopathy syndrome. Phenotype severity is correlated with the residual enzyme activity of ZMPSTE24 and accumulation of prelamin A. We had previously demonstrated that a complete loss of function in ZMPSTE24 was lethal in the neonatal period, whereas compound heterozygous mutations including one PTC and one missense mutation were associated with type B mandibuloacral dysplasia. In this study, we report a 30-year longitudinal clinical survey of a patient harboring a novel severe and complex phenotype, combining an early-onset progeroid syndrome and a congenital myopathy with fiber-type disproportion. A unique homozygous missense ZMPSTE24 mutation (c.281T>C, p.Leu94Pro) was identified and predicted to produce two possible ZMPSTE24 conformations, leading to a partial loss of function. Western blot analysis revealed a major reduction of ZMPSTE24, together with the presence of unprocessed prelamin A and decreased levels of lamin A, in the patient's primary skin fibroblasts. These cells exhibited significant reductions in lifespan associated with major abnormalities of the nuclear shape and structure. This is the first report of MAD presenting with confirmed myopathic abnormalities associated with ZMPSTE24 defects, extending the clinical spectrum of ZMPSTE24 gene mutations. Moreover, our results suggest that defective prelamin A processing affects muscle regeneration and development, thus providing new insights into the disease mechanism of prelamin A-defective associated syndromes in general.
Assuntos
Anormalidades Múltiplas/genética , Acro-Osteólise/genética , Lamina Tipo A/genética , Lipodistrofia/genética , Proteínas de Membrana/genética , Metaloendopeptidases/genética , Distrofias Musculares/genética , Miopatias Congênitas Estruturais/genética , Proteínas Nucleares/genética , Progéria/genética , Precursores de Proteínas/genética , Anormalidades Múltiplas/fisiopatologia , Acro-Osteólise/complicações , Acro-Osteólise/fisiopatologia , Adulto , Sequência de Aminoácidos , Técnicas de Cultura de Células , Feminino , Fibroblastos , Heterozigoto , Homozigoto , Humanos , Lamina Tipo A/metabolismo , Lipodistrofia/complicações , Lipodistrofia/fisiopatologia , Mandíbula/anormalidades , Mandíbula/fisiopatologia , Proteínas de Membrana/metabolismo , Metaloendopeptidases/metabolismo , Dados de Sequência Molecular , Distrofias Musculares/complicações , Distrofias Musculares/fisiopatologia , Mutação , Mutação de Sentido Incorreto , Miopatias Congênitas Estruturais/complicações , Miopatias Congênitas Estruturais/fisiopatologia , Proteínas Nucleares/metabolismo , Fenótipo , Progéria/complicações , Progéria/fisiopatologia , Precursores de Proteínas/metabolismoAssuntos
Deformidades Congênitas da Mão/complicações , Acro-Osteólise/complicações , Acro-Osteólise/diagnóstico por imagem , Adulto , Reabsorção Óssea/complicações , Reabsorção Óssea/diagnóstico por imagem , Deformidades Congênitas da Mão/diagnóstico por imagem , Humanos , Úmero/diagnóstico por imagem , Lipodistrofia/complicações , Lipodistrofia/diagnóstico por imagem , Masculino , Mandíbula/anormalidades , Mandíbula/diagnóstico por imagem , Ossos Pélvicos/diagnóstico por imagem , RadiografiaRESUMO
A case of exuberant acroosteolysis and subcutaneous tissue calcinosis in the absence of skin involvement is presented. Different hypotheses are discussed following the clinical unfolding of the case in practice.
Assuntos
Acro-Osteólise/diagnóstico , Calcinose/diagnóstico , Tendão do Calcâneo/diagnóstico por imagem , Tendão do Calcâneo/patologia , Acro-Osteólise/complicações , Idoso , Calcinose/complicações , Diagnóstico Diferencial , Feminino , Falanges dos Dedos da Mão/diagnóstico por imagem , Falanges dos Dedos da Mão/patologia , Doenças Genéticas Inatas/diagnóstico , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Angioscopia Microscópica , Unhas/irrigação sanguínea , Radiografia , Escleroderma Sistêmico/diagnóstico , Dermatopatias/patologia , Falanges dos Dedos do Pé/diagnóstico por imagem , Falanges dos Dedos do Pé/patologiaRESUMO
Wegener's granulomatosis is a multisystem disorder involving small- and medium-sized vessels, leading to granuloma formation and involvement of upper and lower respiratory tract with or without glomerulonephritis. However, limited forms of angiitis and granulomatosis of the Wegener's type with oligosymptomatic and atypical site involvement are known to occur. We present here a rare case of limited form of angiitis and granulomatosis of Wegener's type who presented sequentially with spontaneous resorption of digits with acro-osteolysis and mononeuritis multiplex over a period of 10 months. His vasculitic workup revealed high proteinase 3 antibodies (c-ANCA) titers and an almost asymptomatic lung involvement, detected on high-resolution computed tomography of chest. The patient was aggressively treated with immunosuppressive therapy, following which he showed good improvement.