How does age at onset influence the outcome of autoimmune diseases?

The age at onset refers to the time period at which an individual experiences the first symptoms of a disease. In autoimmune diseases (ADs), these symptoms can be subtle but are very relevant for diagnosis. They can appear during childhood, adulthood or late in life and may vary depending on the age at onset. Variables like mortality and morbidity and the role of genes will be reviewed with a focus on the major autoimmune disorders, namely, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes mellitus (T1D), Sjögren's syndrome, and autoimmune thyroiditis (AITD). Early age at onset is a worst prognostic factor for some ADs (i.e., SLE and T1D), while for others it does not have a significant influence on the course of disease (i.e., SS) or no unanimous consensus exists (i.e., RA and MS)

Clinicopathological Conference: Complications of Rheumatoid Arthritis

Clinicopathlogical conference transcript from the Medical College of Virginia. Discussants include P. Franklin Mullinax and R. Page Hudson

A national cohort study on pediatric Behçet's disease: Cross-sectional data from an Italian registry

21noBACKGROUND: Behçet's disease is a rare multi-systemic inflammatory disease with unknown etiology which involves principally oral and genital mucosa, skin and eyes. Average age at onset of the disease is about 25-30 years, but it may be diagnosed before the age of 16. It is not very rare in Italy, even though there are limited data concerning epidemiology. Aim of this study is to describe the baseline data of an Italian cohort of patients with as having BD or probable BD. METHODS: We described the baseline data of the first national epidemiological study on children coming from 16 Italian Pediatric Rheumatologic Centers diagnosed by the treating physicians as having Behçet's Disease. Data on demographic characteristics, clinical features and therapy were collected. We then compared our findings to those of international pediatric cohort studies and also retrospectively evaluated the ability to diagnose BD using ISG, ICBD and, for the first time, the new PEDBD criteria. RESULTS: The study included 110 patients (62 M, 48F). Average age at onset was 8.34±4.11 years. The frequencies of signs/symptoms were: recurrent oral aphtosis 94.5%, genital ulcers 33.6%, ocular 43.6%, gastrointestinal 42.7%, musculoskeletal 42.7%, neurological 30.9% and vascular involvement 10%. Thirty-two patients (29.1%) fulfilled ISG, 78 (70.9%) ICBD, 50 (45.5%) PEDBD criteria and 31 (28%) didn't fulfill any of them. The most frequently used treatments were colchicine and corticosteroids followed by immunosuppressants. Four patients received biologic therapy (anti TNF-α and anti-IL-1) to treat severe organ involvement. CONCLUSIONS: Recurrent oral aphtosis was the most frequent clinical manifestation, followed by ocular involvement. Gastrointestinal lesions were more frequent in Italy than in non-European countries as opposed to genital ulcers. Skin, ocular and vascular manifestations had a higher frequency in males and genital ulcers in females. Constitutional symptoms were present in 44.5% and recurrent fever in one third of our population.openopenGallizzi, Romina*; Pidone, Caterina; Cantarini, Luca; Finetti, Martina; Cattalini, Marco; Filocamo, Giovanni; Insalaco, Antonella; Rigante, Donato; Consolini, Rita; Maggio, Maria Cristina; Civino, Adele; Martino, Silvana; Olivieri, Alma Nunzia; Fabio, Giovanna; Pastore, Serena; Mauro, Angela; Sutera, Diana; Trimarchi, Giuseppe; Ruperto, Nicolino; Gattorno, Marco; Cimaz, RolandoGallizzi, Romina; Pidone, Caterina; Cantarini, Luca; Finetti, Martina; Cattalini, Marco; Filocamo, Giovanni; Insalaco, Antonella; Rigante, Donato; Consolini, Rita; Maggio, Maria Cristina; Civino, Adele; Martino, Silvana; Olivieri, Alma Nunzia; Fabio, Giovanna; Pastore, Serena; Mauro, Angela; Sutera, Diana; Trimarchi, Giuseppe; Ruperto, Nicolino; Gattorno, Marco; Cimaz, Roland

Rubella rheumatism

A journal article on an outbreak of Rubella Rheumatism in urban areas of Southern Rhodesia in the 1950's

Managing the adverse events of intravesical bacillus Calmette-Guérin therapy

This paper provides recommendations on the management of complications arising from intravesical treatment with bacillus Calmette-Guérin (BCG) for nonmuscle-invasive bladder tumors. There is minimal recommendations currently available as randomized trials on the side effects of intravesical BCG are lacking and severe complications are usually described in case reports only. All physicians giving intravesical BCG should be aware of the possible complications that could arise and how to treat these. The incidence of bladder irritation, general malaise, and fever is very high, while severe complications remain rare. Approximately 8% of patients have to stop treatment because of these complications. BCG infections and reactions can occur anywhere in the body, and may happen straight away or even several months or years after BCG treatment, making early diagnosis difficult. Additionally, correct diagnosis is hampered by the uncertain appearance of BCG in tissue and body fluid. An essential step in the management complications arising from BCG is written information for both the family doctor and the patient on the possible adverse events and their management. Recent data demonstrated that none of the earlier advocated methods to prevent BCG toxicity are valid: lowering the dose, tuberculostatic drugs, or oxybutynin. Severe complications are treated with three or four tuberculostatics over 3-12 months, depending on the severity of the situation. Corticosteroids are an essential therapy in BCG septicemia. Nonsteroidal anti-inflammatory drugs and corticosteroids can manage efficiently the immunological complications

Estudo comparativo entre as manifestações oftalmológicas, sorológicas e resposta terapêutica de pacientes com esclerite isolada e esclerite associada a doenças sistêmicas

INTRODUCTION: Scleritis is a rare, progressive and serious disease, the signs of which are inflammation and edema of episcleral and scleral tissues and is greatly associated with systemic rheumatoid diseases. PURPOSE: To perform a prospective and comparative study between ophthalmologic manifestations, serologic findings and therapeutic response of patients with isolated scleritis and scleritis associated with systemic rheumatoid disease. METHODS: Thirty-two outpatients with non-infectious scleritis were studied, from March 2006 to March 2008. The treatment was corticoid eye drops associated with anti-inflammatory agents, followed by systemic corticoids and immunosuppressive drugs if necessary, was considered successful after six months without scleritis recurrence. RESULTS: Fourteen of 32 patients had scleritis associated with systemic rheumatoid disease, of which nine had rheumatoid arthritis, two systemic lupus erythematosus, one Crohn's disease, one Behçet's disease and one gout. There were no difference in relation to involvement and ocular complications, there was predominance of nodular anterior scleritis and scleral thinning was the most frequent complication. The scleritis associated with systemic rheumatoid disease group had 64.3% of autoantibodies, versus 27.8% among those with isolated scleritis and this difference was statistically significant. In the isolated scleritis group 16.7% used anti-inflammatory, 33.3% corticosteroids, 27.8% corticosteroids with one immunosuppressive drug, 5.5% two immunosuppressive drugs, 16.7% corticosteroids with two immunosuppressive drugs and 33.3% pulse of immunosuppressive drugs, there was remission in 88.9%. In the scleritis associated with systemic rheumatoid disease group 7.1% used anti-inflammatory, 7.1% corticosteroids, 50% corticosteroids with one immunosuppressive drug, 7.1% two immunosuppressive drugs and 22.2% pulse of immunosuppressive drugs, 100% had treatment success. CONCLUSION: Prevalence of unilateral nodular scleritis was noted in both groups and higher rates of all the parameters tested were noted in the scleritis associated with systemic rheumatoid disease group. There were no differences between the groups with respect to the use of immunosuppressive drugs and therapeutic response, which was fully satisfactory in the scleritis associated with systemic rheumatoid disease group and satisfactory in the isolated scleritis group.INTRODUÇÃO: Esclerite é uma doença grave, rara e progressiva, que envolve inflamação e edema dos tecidos episcleral superficial, profundo e escleral e está associada com doenças sistêmicas reumatológicas em muitos casos. OBJETIVOS: Realizar um estudo prospectivo comparativo entre as manifestações oftalmológicas, achados sorológicos e resposta terapêutica de pacientes com esclerite isolada e com esclerite associada a doenças sistêmicas reumatológicas. MÉTODOS: Trinta e dois pacientes com esclerite não infecciosa participaram do estudo, de março de 2006 a março de 2008. O tratamento realizado baseou-se no uso de colírios de corticoides associados aos anti-inflamatórios não-hormonais, seguidos de corticoides sistêmicos e imunossupressores, se necessário. O sucesso do tratamento foi considerado como seis meses sem crises de esclerite. RESULTADOS: Quatorze dos 32 pacientes apresentaram esclerite associada à doença sistêmica, dos quais nove com artrite reumatóide, dois com lúpus eritematoso sistêmico, um com doença de Crohn, um com doença de Behçet e um com gota. Não houve diferenças em relação ao envolvimento ocular e suas complicações, predominando a esclerite anterior nodular e o afinamento escleral, respectivamente. O grupo com esclerite associada a doenças sistêmicas apresentou 64,3% de positividade de autoanticorpos contra 27,8% no grupo com esclerite isolada, sendo tal diferença estatisticamente significante. No grupo com esclerite isolada, 16,7% fez uso de apenas anti-inflamatórios, 33,3% de corticoide sistêmico, 27,8% de corticoide com um imunossupressor, 5,5% dois imunossupressores, 16,7% corticoide com dois imunossupressores e 33,3% pulsoterapia com imunossupressor; sendo que houve sucesso do tratamento em 88,9%. No grupo com esclerite associada à doença sistêmica, 7,1% fez uso de anti-inflamatórios, 7,1% corticoide sistêmico, 50% corticoide com um imunossupressor, 7,1% dois imunossupressores e 22,2% pulsoterapia com imunossupressor; com 100% de sucesso no tratamento nesse grupo. CONCLUSÃO: Em ambos os grupos houve predomínio da esclerite nodular unilateral e o grupo com esclerite associada a doença sistêmica apresentou taxas maiores de todos os autoanticorpos testados. Não houve diferença entre os grupos em relação ao uso de imunossupressores e à resposta terapêutica, a qual foi totalmente satisfatória no grupo com esclerite associada à doença sistêmica e satisfatória no grupo com esclerite isolada.Universidade Federal de São Paulo (UNIFESP)Universidade de Santo AmaroUniversidade Federal de São Paulo (UNIFESP) Departamento de Oftalmologia Setor de Doenças Externas Oculares e CórneaUNIFESP, Depto. de Oftalmologia Setor de Doenças Externas Oculares e CórneaSciEL

Audio-vestibular symptoms in systemic autoimmune diseases

Immune-mediated inner ear disease can be primary, when the autoimmune response is against the inner ear, or secondary. The latter is characterized by the involvement of the ear in the presence of systemic autoimmune conditions. Sensorineural hearing loss is the most common audiovestibular symptom associated with systemic autoimmune diseases, although conductive hearing impairment may also be present. Hearing loss may present in a sudden, slowly, rapidly progressive or fluctuating form, and is mostly bilateral and asymmetric. Hearing loss shows a good response to corticosteroid therapy that may lead to near-complete hearing restoration. Vestibular symptoms, tinnitus, and aural fullness can be found in patients with systemic autoimmune diseases; they often mimic primary inner ear disorders such as Menière’s disease and mainly affect both ears simultaneously. Awareness of inner ear involvement in systemic autoimmune diseases is essential for the good response shown to appropriate treatment. However, it is often misdiagnosed due to variable clinical presentation, limited knowledge, sparse evidence, and lack of specific diagnostic tests. The aim of this review is to analyse available evidence, often only reported in the form of case reports due to the rarity of some of these conditions, of the different clinical presentations of audiological and vestibular symptoms in systemic autoimmune diseases

The genetics of experimental arthritis in rodents

Unravelling the genetic susceptibility to complex autoimmune diseases and understanding these pathologies on a mechanistic level are major obstacles to improve our possibilities for therapeutic intervention and an increase in the quality of life of affected patients. Studies in experimental rodent models, that can be run under stable environmental conditions, which itself can be subjected to experimental manipulation, and in cohorts of potentially unlimited size, hold significant promise for the understanding of genes and pathways involved in complex autoimmune diseases. In this thesis, which is based on five scientific manuscripts, we initially investigated the influence of the genetic background on the ability to detect three major genetic loci (Pia4/Cia12, Pia5/Cia3, Pia7/Cia13) for pristane induced arthritis (PIA) in the rat. We also investigated the effect of Pia1, which includes the RT1 region (major histocompatibility complex (MHC) in the rat). We could show that the major arthritis regulator NCF1 as well as the MHC are silent in certain genetic backgrounds, whereas their genetic effect on PIA susceptibility can be detected in other, distinct genetic setups, arguing for the importance of genetic interactions between MHC and non-MHC genes for PIA development. In the second and third paper, we used a unique approach with a heterogeneous stock (HS) derived inbred-outbred mouse cohort that had been backcrossed to the arthritis susceptible C57BL10/Q (BQ) mouse strain, in order to map clinical phenotypes and the autoantibody response during collagen induced arthritis (CIA) development. We defined numerous novel loci and fine mapped already described quantitative trait loci (QTL) associated with clinical disease and/or autoantibody production providing the to date most comprehensive mapping study in CIA. The papers 4 and 5 concern the positional identification of candidate genes for the CIA loci Cia21 and Cia22 in the mouse. We propose the costimulatory molecule CD2 as a female specific genetic risk factor for autommunity in the joint and the central nervous system (CNS). We also pinpoint the chitinase like gene Chi3l3, also denoted as Ym1, as an important immunomodulator in experimental murine arthritis models based on both active immunization with collagen (CII) and passive transfer of arthritogenic antibodies. Hopefully, the findings presented in this thesis will have clinical implications based on the novel genetic targets, we identified. In addition, our data demonstrate the difficulties and pitfalls that are associated with gene identification using a hypothesis free positional cloning approach in experimental rodent populations