A evolução do diagnóstico da doença mista do tecido conjuntivo / Evolution of the diagnosis of mixed connective tissue disease

A Doença Mista do Tecido Conjuntivo (DMTC) é uma doença autoimune crônica composta por um misto de quatro doenças: Lúpus Eritematoso Sistêmico, Esclerose Sistêmica, Dermatomiosite/Polimiosite e Artrite Reumatoide. Por se tratar de uma combinação de doenças autoimunes o diagnóstico é bastante complexo. Atualmente existem quatro combinações sugeridas por diferentes autores para a realização de um diagnóstico preciso, são eles: Kasukawa, Alarcón-Segovia e Villareal, Kahn e Appeboom e Sharp. Desde a sua descoberta em 1972 por Sharp, passaram-se 46 anos e desta forma o objetivo desta revisão foi verificar a evolução do diagnóstico da DMTC desde a sua descoberta até a atualidade. Para isso utilizou-se sites de busca PUBMED e SCIELO. Por se tratar de uma doença autoimune que leva ao desenvolvimento de um quadro inflamatório crônico utilizou-se a ferramenta STRING que permite a análise da interação de proteínas. Até a presente data, não existe um consenso de qual critério deve ser usado para o diagnóstico correto e eficiente desta doença. A baixa relação de interações observadas a partir da ferramenta STRING demonstra que ainda não existem dados suficientes na literatura para que a ligação entre proteínas marcadoras e a DTMC possa ser estabelecida. (AU)

Mixed connective tissue disease (MCTD) is a chronic autoimmune disorder consisting of a mixture of four diseases: systemic lupus erythematosus, systemic sclerosis, dermatomyositis/polymyositis, and rheumatoid arthritis. Because it is a combination of different autoimmune disorders its diagnosis is quite complex. Currently there are four combinations suggested by the following authors to establish an accurate diagnosis: Kasukawa, Alarcón-Segovia & Villareal, Kahn, and Appeboom & Sharp. It has been 46 years since Sharp reported the disease in 1972 and thus the purpose of this review was to investigate the evolution of the diagnosis of MCTD since then. PubMed and SciELO databases were used for this investigation. Because MCTD is an autoimmune disease that leads to the development of a chronic inflammatory condition, the STRING tool was used to allow the analysis of protein interaction. To date, there is no consensus as to what criterion should be used for a correct and efficient diagnosis of this disease. The low ratio of interactions observed from the STRING tool demonstrates that there is not yet enough data in the literature for establishing the binding between marker proteins and MCTD. (AU)

Sjogren's syndrome: An underdiagnosed condition in mixed connective tissue disease

OBJECTIVE: To determine the prevalence of sicca symptoms, dry eye, and secondary Sjögren's syndrome and to evaluate the severity of dry eye in patients with mixed connective tissue disease. METHODS: In total, 44 consecutive patients with mixed connective tissue disease (Kasukawa's criteria) and 41 healthy controls underwent Schirmer's test, a tear film breakup time test, and ocular surface staining to investigate dry eye. In addition, the dry eye severity was graded. Ocular and oral symptoms were assessed using a structured questionnaire. Salivary gland scintigraphy was performed in all patients. Classification of secondary Sjögren's syndrome was assessed according to the American-European Consensus Group criteria. RESULTS: The patients and controls had comparable ages (44.7±12.4 vs. 47.2±12.2 years) and frequencies of female gender (93 vs. 95%) and Caucasian ethnicity (71.4 vs. 85%). Ocular symptoms (47.7 vs. 24.4%) and oral symptoms (52.3 vs. 9.7%) were significantly more frequent in patients than in controls. Fourteen (31.8%) patients fulfilled Sjögren's syndrome criteria, seven of whom (50%) did not have this diagnosis prior to study inclusion. A further comparison of patients with mixed connective tissue disease with or without Sjögren's syndrome revealed that the former presented significantly lower frequencies of polyarthritis and cutaneous involvement than did the patients without Sjögren's syndrome. Moderate to severe dry eye was found in 13 of 14 patients with mixed connective tissue disease and Sjögren's syndrome (92.8%). CONCLUSIONS: Sjögren's syndrome, particularly with moderate to severe dry eye, is frequent in patients with mixed connective tissue disease. These findings alert the physician regarding the importance of the appropriate diagnosis of this syndrome in such patients. .

Reunión clínica interhospitales / Diagnosis of mixed connective tissue disease

Se presenta el caso clínico de una paciente de 18 años, catalogado inicialmente como LES, con presencia de Ac antiRNP( +) y otras características que hacían planteable la posibilidad de enfermedad mixta del tejido conectivo (EMTC), quien evoluciona con cuadro de hipertensión arterial severa, llegando a emergencia hipertensiva, en relación a dos episodios de crisis convulsiva tónico-clónicas, no presentando deterioro de función renal. Su cuadro hipertensivo se manejó con uso de inhibidor de enzima convertidora de angiotensina (lECA) logrando normalización de cifras tensionales y desaparición de síntomas neurológicos, sin otros parámetros de enfermedad activa, lo que hizo pensar en la posibilidad de un cuadro similar a la crisis renal esclerodérmica, pero en el contexto de esta paciente con probable EMTC. Apoyaría lo anterior el hecho de la excelente evolución sin necesidad de aumentar la terapia esteroidal, ni de asociar otro inmunosupresor en ese momento.

We present the case of a 18-year-old woman, initially diagnosed with SLE. Laboratory exams were positive for anti RNP antibodies. This and some other characterisitics led to the diagnosis of mixed connective tissue disease (MCTD). She evolved into severe arterial hypertension, reaching hypertensive emergency related to two episodes of convulsive tonic-clonic crisis, without kidney failure. Her hypertension was managed with an angiotensin converting enzyme inhibitor (ACE inhibitor), achieving normal tension parameters and disappearance of the neurologic symptoms, without other parameters of active disease, which made us think of a clinical case similar to scleroderma renal crisis, but in the context of this patient with probable MCTD. This is sustained by the fact that the evolution was excellent without the need to in crease steroidal therapy, nor to associate another immune suppressor at that time.

Síndrome de Sharp o conectivitis mixta / Sharp syndrome or mixed connectivitis

El Síndrome de Sharp es una conectivitis en cuyo cuadro clínico se combinan manifestaciones de varias de las mesenquimopatias más frecuentes. Entre sus principales síntomas destacan el Síndrome de Raynaud; las poliartralgias de manos y las mialgias. El Síndrome de Sharp, generalmente no compromete la piel ni las vísceras y entre ellas especialmente el riñón. En el aspecto inmunológico, es característica la presencia, en el suero, y a título elevados de anticuerpos anti RNP. El pronóstico del Síndrome de Sharp es habitualmente benigno y se describe incluso evoluciones regresivas.

Hipertensão arterial pulmonar nas doenças do tecido conjuntivo / Pulmonary arterial hypertension in connective tissue diseases

A hipertensão arterial pulmonar é uma causa importante de morbidade e mortalidade em pacientes com doenças difusas do tecido conjuntivo. É uma manifestação que ocorre em cerca de 10 por cento a 15 por cento dos pacientes com esclerose sistemica, isolada ou associada à doença intersticial pulmonar, e tem prognóstico ruim. Também pode acometer indivíduos com lúpus eritomatoso sistêmico e doença mista do tecido conjuntivo, e mais raramente artrite reumatóide e miopatias inflamatórias. Na esclerose sistêmica, pela pesquisa obrigatória de hipertensão arterial pulmonar no diagnóstico e seguimneto dos pacientes, é frequente o disgnóstico de formas precoces da doença.

Pulmonary hypertension not a major feature of early mixed connective tissue disease: a prospective clinicoserological study.

BACKGROUND: Mixed connective tissue disease (MCTD) has features common to lupus, scleroderma and myositis with high levels of antibodies to U1 ribonucleoprotein (U1 RNP). Identification of a high incidence of pulmonary artery hypertension (PAH) has changed its prospect. We report the largest series from India. SETTINGS AND DESIGN: Rheumatology unit of a tertiary care centre in India; prospective. MATERIALS AND METHODS: Patients seen between January 2002 and June 2004, satisfying the Kasukawa criteria were enrolled. All patients had a complete laboratory work-up including pulmonary function test, 2-D echocardiography, and Schirmer's test, antinuclear antibodies (ANA) and antibodies to extractable nuclear antigens. HRCT of chest was done where indicated. All patients were given standard treatment and followed up regularly. RESULTS: Out of 1500 patients, thirteen (one male) were diagnosed to have MCTD. The median follow-up period was 18 months [Interquartile range (IQR) 12-22]. The median age of onset of symptoms was 36 years (IQR 22-39) and the median duration of disease was three years (IQR 1.75-4). The most common manifestation was polyarthritis followed by puffy fingers. Sjogren's syndrome, dysphagia and interstitial lung disease, was present in four, three and two patients respectively. Two patients each had myositis and migraine. None had PAH, serositis or renal involvement. Arthritis, puffy fingers and Raynaud's phenomenon were the most common manifestations at onset. All patients were positive for ANA and anti U1 RNP. Two patients each had antibodies to Sm and SSA. Response to treatment also was noted. CONCLUSION: Pulmonary artery hypertension is not common in early MCTD.

Colagenopatia y meningitis recurrente en una paciente de 88 años / Collagen diseases and recurrent meningitis in an 88 year old patient

La meningitis aséptica recurrente (MAR) en ancianos es rara y generalmente es secundaria a drogas. Su asociación a colagenopatías en ancianos ha sido raramente informada. El Síndrome de Sjögren (SS) en ocasiones afecta el sistema nervioso central, pero la MAR asociada a SS es rara en este grupo etario. Se presenta una paciente de 88 años, autoválida, con antecedentes de xerostomía, xeroftalmos, Raynaud, disfagia y agrandamiento parotídeo recurrente autolimitado. En el año 2001 cursó una meningitis linfocítica y evolucionó con recuperación completa. Un año después volvió a presentar una meningitis linfocítica aséptica. Se descartaroncausas infecciosas. Se demostró FAN 1/160 con patrón nucleolar moteado, Ac anti Ro y anti RNP positivosy anticoagulante lúpico positivo. Se confirmó sequedad ocular y la biopsia de labio fue compatible con SS.Evolucionó con resolución completa en 10 días sin tratamiento. Se interpretó como una enfermedad mixta deltejido conectivo (EMTC) con síntomas predominantemente de SS, que cursó una MAR en su forma pura. La EMTC y el SS deberían ser considerados entre los diagnósticos diferenciales de la MAR, inclusive en ancianos.

Mixed connective tissue disease--clinical and immunological profile.

AIM OF THE STUDY: To study the clinical and immunological profile of mixed connective tissue disease (MCTD) in rheumatic disease population. METHODS: We retrospectively analyzed 6400 cases of rheumatic disease population who took treatment in the Department of Rheumatology, Madras Medical College, Chennai during the period of 1996 to 1999, in which eight cases fulfilled the preliminary diagnostic criteria of mixed connective tissue disease devised by Kasukawa et al. All eight cases were studied in detail. RESULTS: All cases were females between 23 to 50 years of age. Polyarthritis, Raynaud's phenomenon and sclerodactyly were present in all eight patients. Oesophageal abnormalities, pulmonary changes and myositis were present in six patients. Facial erythema was observed in five patients. Alopecia and oral ulcers were seen in four patients. Two patients had pulmonary hypertension and migraine like headache. One patient had diffuse proliferative glomerulonephritis as an interesting feature by renal biopsy. Pleuritis, pericarditis and trigeminal neuropathy with lower cranial nerve palsies were present in one case each. Immunological tests showed presence of antinuclear antibodies and anti U1 ribonucleoprotein (anti U1RNP) antibodies in all eight patients. CONCLUSIONS: Mixed connective tissue disease should be considered as an important syndrome in any patient who presents with heterogeneous clinical presentation and who do not fit into any definite criteria of systemic connective tissue disorders.

Enfermedad Mixta del Tejido Conectivo / Mixed Connective Tissue Disease

Paciente de 35 años que ingresa con un cuadro de gangrena de dedos de ambas manos y ambos pies, con síndrome séptico que motiva la amputación de ambos pies. El estudio de su patología de base indicó una vasculitis, sin trombosis, ni fenómenos específicos, con disminución de las luces arteriales e infiltrados mononucleares, como manifestación de una Enfermedad Mixta del Tejido Conectivo. Se contemplan aspectos clínicos, laboratorio y conducta terapéutica.

Enfermedad mixta del tejido conectivo en niños / Mixed connective tissue disease in children

La enfermedad mixta del tejido conectivo es una enfermedad autoinmune de difícil diagnóstico por tratarse de un síndome de sobreposición de varias enfermedades del tejido conectivo, que nos da una variación extensa en su presentación y evolución clínica, además de que resulta aún poco conocida por muchos médicos. Motivados por ello, se presenta esta revisión de la experiencia clínica del Instituto Nacional de Pediatría con ocho pacientes con esta enfermedad y se compara con los informes previos de la literatura. Se encontró gran similitud en nuestros casos con los informes de pacientes pediáticos, haciendo notar que en ellos su presentación es más grave por la presencia de afección multisistémica y que pueden llegar a requerir un tratamiento agresivo con el uso de esteroides a dosis elevadas e inmunosupresores en los casos graves o que no responden adecuadamente a esteroides. Se presenta el hecho (ya publicado) que varios órganos pueden tener afección subclínica, lo que justifica hacer una evaluación completa del paciente poniendo énfasis en los órganos y sistemas que pueden poner en peligro su vida