"Mixed connective tissue disease": a condition in search of an identity.

Mixed connective tissue disease was first described as a new autoimmune rheumatic disease in 1972 based on the claim of a distinct clinical picture associated with anti-RNP antibody positivity. Subsequently, this new entity has divided opinions in the rheumatology community. We have reviewed recent cohort studies with more than 100 patients, comparing the clinical and immunological features, treatment, prognosis and evolution to well-defined autoimmune rheumatic diseases. We also reviewed clinical features of undifferentiated autoimmune rheumatic diseases based on the most recent studies. After gathering and reviewing these data, we discuss whether the designation "mixed connective tissue disease" should be maintained.

Phosphaturic mesenchymal tumor and related wound problem.

INTRODUCTION: Phosphaturic mesenchymal tumor mixed connective tissue type (PMT/MCT) is the most common type (up to 90%) of phosphaturic mesenchymal tumor (PMT), a rare clinicopathologic entity. Besides overproduction of fibroblast growth factor 23 (FGF23), there is a big variation of immunohistochemical characteristic across types of PMT, which makes it difficult to obtain an early diagnosis of PMT/MCT. As a benign tumor, PMT/MCT usually happens in subcutaneous tissues and leads to nonhealing of wound. A complete excision of PMT/MCT facilitates wound healing. CONCLUSIONS: Review of the existing evidence indicates that early diagnosis of PMT/MCT is critically important when treating PMT/MCT wound. Hence standardization of early diagnosis for PMT/MCT is mandated.

Melkersson-Rosenthal syndrome as an early manifestation of mixed connective tissue disease.

PURPOSE OF REVIEW: We aim to illustrate the potential viability of MCTD as an underlying aetiology of Melkersson-Rosenthal syndrome. The case is probably the first description available in the literature of the Melkersson-Rosenthal as an early manifestation of mixed connective tissue disease. RECENT FINDINGS: The Melkersson-Rosenthal syndrome consists of a triad of recurrent lip and/or face swelling, fissured tongue, and intermittent facial palsy. Mixed connective tissue disease is a multisystemic disorder with overlapping features of systemic lupus erythematosus, scleroderma, and polymyositis, and is differentiated from them by a high titer of antibodies to ribonucleoprotein. The paper presents a case report of Melkersson-Rosenthal syndrome with an onset in childhood that derived from vasculitis that turned out to be an early manifestation of mixed connective tissue disease. We used MRI to evaluate patient's brain structure and Immunoblot Ena Profil 1 test to test serum autoantibodies level. The patient has a typical for Melkersson-Rosenthal syndrome triad of symptoms: bilateral facial nerve palsy, lingua plicata and facial oedema. Both TC and MRI of the head show no changes as well as laboratory tests except Anti-SS-A (Anti-Ro) and Anti-RNP autoantibody serum level that was highly positive. Neurological involvement of the MCTD usually includes, according to the frequency of the occurrence, trigeminal neuralgia, headaches, sensorineural hearing, cerebral haemorrhage, transverse myelitis, cauda equina syndrome, retinal vasculitis, progressive multifocal encephalopathy, and demyelinating neuropathy. For clinical practice it is important to remember that Melkersson-Rosenthal syndrome can also be the neurological manifestation of MCTD, especially when accompanied by other systemic symptoms.

Selected Aspects in the Pathogenesis of Autoimmune Diseases.

Autoimmune processes can be found in physiological circumstances. However, they are quenched with properly functioning regulatory mechanisms and do not evolve into full-blown autoimmune diseases. Once developed, autoimmune diseases are characterized by signature clinical features, accompanied by sustained cellular and/or humoral immunological abnormalities. Genetic, environmental, and hormonal defects, as well as a quantitative and qualitative impairment of immunoregulatory functions, have been shown in parallel to the relative dominance of proinflammatory Th17 cells in many of these diseases. In this review we focus on the derailed balance between regulatory and Th17 cells in the pathogenesis of autoimmune diseases. Additionally, we depict a cytokine imbalance, which gives rise to a biased T-cell homeostasis. The assessment of Th17/Treg-cell ratio and the simultaneous quantitation of cytokines, may give a useful diagnostic tool in autoimmune diseases. We also depict the multifaceted role of dendritic cells, serving as antigen presenting cells, contributing to the development of the pathognomonic cytokine signature and promote cellular and humoral autoimmune responses. Finally we describe the function and role of extracellular vesicles in particular autoimmune diseases. Targeting these key players of disease progression in patients with autoimmune diseases by immunomodulating therapy may be beneficial in future therapeutic strategies.

Lifestyle and other related factors for the development of mixed connective tissue disease among Japanese females in comparison with systemic lupus erythematosus.

OBJECTIVE: The etiology of mixed connective tissue disease (MCTD) has not been elucidated in detail. Case control studies of MCTD and systemic lupus erythematosus (SLE) were conducted in order to compare factors related to these two diseases. METHODS: We selected 48 MCTD and 54 SLE female patients throughout Japan from 2009 to 2010. Controls were 182 female patients who visited the clinics of general internal medicine during the study periods. RESULTS: Smoking and walking a longer time showed an increased age-adjusted risk for MCTD as well as SLE. On the other hand, frequent intake of bread increased the risk of MCTD and high intake of green tea decreased the risk of MCTD. Even after an additional adjustment of smoking and drinking, frequent intake of bread increased the risk of MCTD, while walking increased the risk of SLE. CONCLUSION: The present study suggests that Westernization of dietary habits (i.e. frequent intake of bread and low intake of green tea) may increase the risk of MCTD, while walking may increase the risk of SLE (probably due to exposure to the sunlight) among Japanese females. Further studies are needed to confirm the result of the present study.

The spectrum of lung involvement in collagen vascular-like diseases following allogeneic hematopoietic stem cell transplantation: report of 6 cases and review of the literature.

Multisystem autoimmune diseases occurring after allogeneic hematopoietic stem cell transplantation are infrequent, late-onset manifestations that resemble well-defined collagen vascular disorders. Because the lung is frequently involved in the course of connective tissue disorders, we focused on lung manifestations occurring in autoimmune diseases following allogeneic stem cell transplantation. In the present series, we report 6 patients with systemic lupus erythematous, mixed connective tissue disease, Sjögren syndrome, polymyositis, and ANCA-positive vasculitis who presented with a spectrum of pulmonary manifestations affecting the airways, lung parenchyma, and probably respiratory muscles. We identified 3 different histopathologic patterns of interstitial pneumonia consistent with the underlying autoimmune disorder: lymphocytic interstitial pneumonia and non-specific interstitial pneumonia in 2 patients with Sjögren syndrome and diffuse alveolar damage in 1 patient with ANCA-positive vasculitis. These lung manifestations had poor prognoses. Further studies are needed to determine the optimal therapy for these complications.

[A 56-year-old female patient with Raynaud's syndrome, increased liver enzymes and neuropsychiatric symptoms]. / 56-jährige Patientin mit Raynaud-Symptomatik, erhöhten Leberenzymen und neuropsychiatrischen Symptomen.

CASE HISTORY: A 56-year-old woman presented with increased liver enzymes (GPT, GOT), arthralgias, Raynaud's syndrome and disturbance of sleep and concentration. FINDINGS AND DIAGNOSIS: Serology and liver biopsy indicated chronic hepatitis C infection (HCV) and viral-induced liver cirrhosis with unremarkable liver synthesizing parameters. An HCV-triggered cryoglobinemia was excluded, but high elevated antinuclear antibodies (ANA) and anti-RNP autoantibodies, typical serological parameters of mixed tissue collagenous (Sharp}s disease), were detectable. Magnetic resonance spectroscopy (H-MRS) was performed to differentiate between cerebral vasculitis and mild hepatic encephalopathy. This detected abnormal pattern of cerebral metabolites (myo-inositol and choline), is specific for HE. TREATMENT AND COURSE: After onset of an antiviral therapy (terferon/ribavirin), low protein diet with supplementation of l-ornithine-l-aspartate the arthralgia and neuropsychiatric symptoms rapidly improved and HCV-RNA PCR became negative. Unfortunately, after cessation of antiviral treatment the patient had a relapse of HCV with a worsening of the arthralgia and the Raynaud symptoms (HCV-triggered Sharp}s disease). CONCLUSION: Even in patients with mildly abnormal liver function and liver cirrhosis it is important to consider (mild) hepatic encephalopathy if neuropsychiatric symptoms occur.

Mixed connective tissue disease.

Mixed connective tissue disease (MCTD) was first described in 1972 as a disease syndrome with overlapping features of systemic sclerosis, systemic lupus erythematosus (SLE) and polymyositis associated with antibodies to RNAse sensitive extractable nuclear antigen. When the antigen was subsequently characterized as polypeptides on the U1 ribonuclear protein component of the splicesosome (U1RNP), MCTD became the first rheumatic disease syndrome to be defined by a serologic test. Clinical features include a high frequency of Raynaud's syndrome, swollen hands, sclerodactyly, arthritis, polymyositis and interstitial lung disease. Over the last 30 years there has been a continuing debate as to whether MCTD constitutes a 'distinct clinical entity'. Here, I will review the pathological, immunogenetic and clinical features of MCTD and conclude that the debate remains unresolved. The early misconception that it has a relatively good prognosis has not stood the test of time with long-term follow-up studies. These have identified a tendency for MCTD to evolve into SLE or systemic sclerosis and highlighted pulmonary hypertension and scleroderma renal crisis as important causes of death. Providing it is realized that our appreciation of the clinical features associated with anti-U1RNP have evolved over time, MCTD remains a useful concept in clinical practice. Whether it can be credited with the term 'disease' awaits the demonstration of common etiopathological events underlying the development of antibodies to U1 RNP and their associated clinical features.

Does mixed connective tissue disease exist? Yes.

For patients who have combined features of rheumatoid arthritis, the limited cutaneous form of systemic sclerosis, and inflammatory myopathies, the concept of mixed connective tissue disease (MCTD) often helps to predict and diagnose organ problems and to educate the patient accordingly. With high titer IgG antibodies to U1 ribonucleoprotein (U1-snRNP), this concept is supported by a specific serologic marker, and autoantibodies to U1-snRNP and to heterogeneous nuclear ribonucleoprotein (hnRNP)-A2 display MCTD specificity with regard to the recognized epitopes. In addition, the association of MCTD with HLA-DR4 distinguishes it from systemic erythematosus lupus and systemic sclerosis, and speaks to its being a disease entity, rather than a mixture of yet undifferentiated collagen vascular diseases. The authors believe that the concept is useful in daily practice and accurate in the idea that MCTD constitutes a disease entity of its own.

Mixed connective tissue disease: still crazy after all these years.

Mixed connective tissue disease (MCTD) remains a controversial diagnosis. The classification criteria have changed significantly from the original description by Sharp and colleagues in 1972 after follow-up of the original and other MCTD patients. In this article we review the clinical, serologic, and genetic studies of MCTD published in the last 10 years and ask if this term is appropriate.

Pediatric-onset mixed connective tissue disease.

This article discusses the literature on pediatric-onset mixed connective tissue disease (MCTD) and adds 34 new cases. Although not benign, pediatric-onset MCTD carries less mortality than adult-onset disease.

Pregnancy in mixed connective tissue disease.

This article discusses fetal and maternal morbidity in women who have mixed connective tissue disease.

Dermatosesrelacionadas às doenças da tireóide / Skin diseases related to thiroid disease

As disfunçöes tiroidianas, näo raramente, manifestam-se em associaçäo ou induzem ao aparecimento de quadros cutâneos. Em algumas situaçöes, as queixas iniciais ou principais dos pacientes portadores de tiroidopatias säo relatadas como alteraçöes na pele e, assim sendo,os dermatologistas seräo os primeiros médicos a serem consultados. Neste artigo, descrevemos as alteraçöes cutâneas que ocorrem nos pacientes com doenças tiroidianas, tais como: cisto do ducto tireoglosso, metastase cutânea do câncer de tireóide e lesöes näo específicas relacionadas ao hipo e ao hipertiroidismo.

Scleroderma overlap syndromes.

Scleroderma is a connective tissue disease that causes fibrosis and vascular abnormalities, but that also has an autoimmune component. Many patients with scleroderma have a positive antinuclear antibody, and there can be family histories of other connective tissue diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Some patients have features of scleroderma and other autoimmune conditions. This article will review recent literature to help in the understanding of scleroderma with overlap features. Recent reports of scleroderma overlap with rheumatoid arthritis suggest distinct features of diffuse scleroderma with positive Scl-70, pulmonary fibrosis, and later seropositive erosive rheumatoid arthritis. SLE rarely occurs with scleroderma. Sjögren syndrome symptoms are common in scleroderma. In primary Sjögren syndrome, anticentromere antibody positive patients have more Raynaud phenomenon. Antibodies that occur in scleroderma that are thought to be specific are present in other connective tissue diseases. For instance, Scl-70 antibody is reported in as many as 35% of patients with scleroderma but can be present in 25% of patients with SLE. Myositis or myopathy can be features of scleroderma. Scleroderma overlap with polymyositis is frequently anti-PM Scl antibody positive, whereas anti-Jo-1 does not normally occur in the overlap of scleroderma and polymyositis but is usually exclusively positive in polymyositis with arthritis and alveolitis. A better prognosis is found with PM Scl antibody in myositis. Vasculitis is not a typical feature of scleroderma, but has been reported. Eosinophilic fasciitis is rare, and the onset could be associated with simvastatin.

Catatonia: manifestação rara na doença mista do tecido conjuntivo / Catatonia: a rare manifestation in the mixed connective tissue disease

A doença mista do tecido conjuntivo (DMTC) é uma síndrome de superposição de lúpus eritematoso sistêmico, esclerose sistêmica e polimiosite. Na DMTC, 10 a 55 por cento dos pacientes apresentam manifestações neuropsiquiátricas, principalmente nas formas de neuropatia de trigêmeo e meningite asséptica. Psicose é descrita, apresentando-se em todos os relatos sob a forma paranóide. Os autores descrevem o caso de uma paciente com diagnóstico estabelecido de DMTC segundo os critérios de Kasuakawa et al., com acometimento predominantemente miopático e altos títulos de RNP (1:50.000) que, após um ano de tratamento com resultados satisfatórios, apresentou quadro de alucinações visuais e auditivas com delírio paranóide que rapidamente evoluiu para estupor catatônico. De acordo com a revisão de literatura, essa manifestação neuropsiquiátrica até então não era descrita na doença mista do tecido conjuntivo