PBC and related extrahepatic diseases.

Patients with PBC have at least 60% of probability to have an autoimmune extrahepatic condition. The pathogenesis of these conditions includes a common mechanism involving both innate and adaptive immune responses targeting cholangiocytes and different extrahepatic tissues. The recent EASL guidelines recommend the management of these conditions, although detailed practical treatments have not been indicated. Autoimmune extrahepatic conditions may include: rheumatologic, endocrine, pulmonary, gastrointestinal, dermatologic diseases. This review aims to focus the most important extrahepatic autoimmune conditions associated to PBC with practical recommendation regarding diagnostic approach and management.

Síndrome de CREST: presentación de un caso / CREST syndrome: presentation of a case

Como esclerodermia, se designa un grupo de enfermedades y síndromes que tienen como característica común la induración y el engrosamiento cutáneos. El síndrome CREST (calcinosis, fenómeno de Raynaud, alteraciones de la motilidad esofágica, esclerodactilia y telangiectasias) es una forma limitada de esclerodermia. En esta modalidad de la entidad es típico que el síndrome de Raynaud anteceda en años a la presentación del resto de los síntomas de enfermedad. En él pueden aparecer manifestaciones de fibrosis insterticial pulmonar, la cual se evidencia clínicamente por estertores húmedos bibasales, muchas veces sin otra forma de expresión, causa hipertensión pulmonar y fallo miocárdico. Es una enfermedad rara, más frecuente en mujeres que en hombres, de 35 a 50 años de edad. Está descrita en ancianos, pero la forma de CREST es muy infrecuente después de los 25 años. El objetivo fue presentar el caso de una mujer de 55 años de edad con un síndrome de CREST, un cor pulmonale y una evolución favorable. Es una entidad poco frecuente, pero que frente a su evidencia clínica debe insistirse en el diagnóstico positivo. Se trata de un caso interesante pues cursó con hipertensión pulmonar, cor pulmonale y su evolución fue satisfactoria...(AU)

As scleroderma are called a group of diseases and syndromes having as a common characteristic the skin hardening and thickening. The CREST syndrome (calcinosis, Raynaud phenomena, alterations of the esophageal motility, sclerodactily and telangiectasia) is a limited form of scleroderma. In this modality of the entity, it is typical that Raynaud syndrome precedes in years the presentation of the rest of the disease symptoms. There may appear manifestations of interstitial pulmonary fibrosis, clinically evidenced by bibasilar humid rales, without any other clinical expression, and it causes pulmonary hypertension and myocardial failure. It is a rare disease, more frequent in women than in men, aged 35 to 50 years. It is described in elder people, but the CREST form is very infrequent after the age of 25. Our aim was presenting the case of a 55-years-old woman with the CREST syndrome, a cor pulmonale and a favorable evolution. It is a rarely frequent entity, but when there are clinical evidences, we should insist in the positive diagnosis. It is an interesting case because she presented pulmonary hypertension, cor pulmonale and developed successfully...(AU)

Síndrome de CREST: presentación de un caso / CREST syndrome: presentation of a case

Como esclerodermia, se designa un grupo de enfermedades y síndromes que tienen como característica común la induración y el engrosamiento cutáneos. El síndrome CREST (calcinosis, fenómeno de Raynaud, alteraciones de la motilidad esofágica, esclerodactilia y telangiectasias) es una forma limitada de esclerodermia. En esta modalidad de la entidad es típico que el síndrome de Raynaud anteceda en años a la presentación del resto de los síntomas de enfermedad. En él pueden aparecer manifestaciones de fibrosis insterticial pulmonar, la cual se evidencia clínicamente por estertores húmedos bibasales, muchas veces sin otra forma de expresión, causa hipertensión pulmonar y fallo miocárdico. Es una enfermedad rara, más frecuente en mujeres que en hombres, de 35 a 50 años de edad. Está descrita en ancianos, pero la forma de CREST es muy infrecuente después de los 25 años. El objetivo fue presentar el caso de una mujer de 55 años de edad con un síndrome de CREST, un cor pulmonale y una evolución favorable. Es una entidad poco frecuente, pero que frente a su evidencia clínica debe insistirse en el diagnóstico positivo. Se trata de un caso interesante pues cursó con hipertensión pulmonar, cor pulmonale y su evolución fue satisfactoria...

As scleroderma are called a group of diseases and syndromes having as a common characteristic the skin hardening and thickening. The CREST syndrome (calcinosis, Raynaud phenomena, alterations of the esophageal motility, sclerodactily and telangiectasia) is a limited form of scleroderma. In this modality of the entity, it is typical that Raynaud syndrome precedes in years the presentation of the rest of the disease symptoms. There may appear manifestations of interstitial pulmonary fibrosis, clinically evidenced by bibasilar humid rales, without any other clinical expression, and it causes pulmonary hypertension and myocardial failure. It is a rare disease, more frequent in women than in men, aged 35 to 50 years. It is described in elder people, but the CREST form is very infrequent after the age of 25. Our aim was presenting the case of a 55-years-old woman with the CREST syndrome, a cor pulmonale and a favorable evolution. It is a rarely frequent entity, but when there are clinical evidences, we should insist in the positive diagnosis. It is an interesting case because she presented pulmonary hypertension, cor pulmonale and developed successfully...

Cranial nerve VIII involvement in a patient with progressive systemic sclerosis.

Systemic sclerosis is a multisystem disorder characterized by abundant fibrosis of the skin, blood vessels, and visceral organs. Cranial nerve involvement is an uncommon feature of this connective tissue disorder, and when it occurs it is the trigeminal nerve that is primarily affected. We report an elderly woman who presented with sensorineural hearing loss and was then diagnosed with the CREST syndrome of progressive systemic sclerosis (calcinosis cutis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia). Involvement of the eighth cranial nerve with scleroderma and CREST syndrome is rare, but appears to be the cause of sensorineural hearing loss in our patient.

Fetal microchimerism in primary biliary cirrhosis.

BACKGROUND/AIMS: Recent studies have suggested a role of fetal microchimerism in the pathogenesis of scleroderma. The present study investigated the potential role of fetal microchimerism in primary biliary cirrhosis (PBC), a closely related disease. METHODS: A quantitative nested polymerase chain reaction was used to detect Y-chromosome sequences in the peripheral blood or the liver of PBC women and controls having male children and no transfusion or miscarriage history. RESULTS: Male microchimerism was found in the peripheral blood from 45% (9 of 20) of PBC women and 25% (5 of 20) of healthy controls matched for the number of male children and age of the youngest son (p=0.28), and in the liver-biopsy specimens from 33% (5 of 15) of PBC women and 32% (8 of 25) of controls. The level of chimerism did not differ between patients and controls either in blood or in liver. Microchimerism was not related to the severity of the disease but was more frequent in PBC patients with anticentromere antibodies (p=0.049). CONCLUSIONS: Fetal microchimerism does not seem to play a major role in most cases of PBC. However, the association with anticentromere antibodies suggests a possible role in the subgroup of patients with CREST syndrome or scleroderma.

Clinical significance of anticentromere antibodies in patients with systemic lupus erythematosus.

OBJECTIVE: To clarify the clinical significance of anticentromere antibodies (ACA) in patients with systemic lupus erythematosus (SLE). METHODS: Two hundred sixteen patients with SLE who were treated in our department were surveyed cross sectionally for the presence of ACA using indirect immunofluorescence on HEp-2 cell lines. ACA were identified by their discrete speckled pattern. Antibodies to the major centromere protein, CENP-B, were also studied with ELISA. Serial determinations of anti-CENP-B were carried out using stored serum samples, if available. RESULTS: ACA were recognized in 12 (5.6%) patients with SLE. All patients were receiving steroid therapy, with a mean dose of prednisolone of 14.4 mg/day. These patients also tested positive for anti-CENP-B with high titers despite the low serological disease activity in most. Three or more CREST features were observed in 2 patients and 2 others had no such features. Both patients without CREST features had a relatively short disease duration. The age at onset of SLE was significantly higher and Raynaud's phenomenon was more frequent in patients with ACA than in patients without ACA. In 8 of 10 patients tested, retrospective analysis using stored sera revealed no consistent change in anti-CENP-B titers over time. CONCLUSION: The presence of ACA in patients with SLE is apparently more frequent than previously believed. Patients with SLE with ACA may be a distinct subgroup. A longterm followup is warranted to fully determine the clinical significance of ACA in patients with SLE.

The kinetochore of higher eucaryotes: a molecular view.

This review summarizes results concerning the molecular nature of the higher eucaryotic kinetochore. The first major section of this review includes kinetochore proteins whose general functions remain to be determined, precluding their entry into a discrete functional category. Many of the proteins in this section, however, are likely to be involved in kinetochore formation or structure. The second major section is concerned with how microtubule motor proteins function to cause chromosome movement. The microtubule motors dynein, CENP-E, and MCAK have all been observed at the kinetochore. While their precise functions are not well understood, all three are implicated in chromosome movement during mitosis. Finally, the last section deals with kinetochore components that play a role in the spindle checkpoint; a checkpoint that delays mitosis until all kinetochores have attached to the mitotic spindle. Brief reviews of kinetochore morphology and of an important technical breakthrough that enabled the molecular dissection of the kinetochore are also included.

[Influence of age on the clinical and biological characteristics of systemic scleroderma]. / Influence de l'âge sur les caractéristiques cliniques et biologiques de la sclérodermie systémique.

PURPOSE: The present study was aimed at assessing the influence of age on clinical and biological features of systemic sclerosis. METHODS: This retrospective study included 151 consecutive patients with systemic sclerosis. The median age at diagnosis was 50.0 years (range: 10-84 years). Patients were divided into two groups according to their age (lower than 50.0 years of age: 73 patients, equal to or above 50 years of age: 78 patients). The following features were compared between the two groups: gender, disease duration, extent of skin sclerosis, Crest syndrome, lung fibrosis, secondary Sjögren's syndrome, antinuclear, anticentromere, and anti-Scl70 antibodies. RESULTS: The disease duration was significantly higher in patients over 50 years of age (7.1 +/- 6.8 years vs 5.5 +/- 5.0 years, P < 0.05). Crest syndrome, secondary Sjögren's syndrome and anticentromere antibodies were significantly more common in patients over 50 years of age (17/73 vs 30/78, P < 10(-2); 9/73 vs 20/78, P < 10(-2), and 19/73 vs 31/78, P < 0.05; respectively). Anti-Scl70 antibodies were significantly more common in patients under 50 years of age (17/73 vs 10/78, P < 10(-2)). No significant difference was found in regard to the other features. CONCLUSION: The clinical and biological patterns of systemic sclerosis are different according to the age at disease onset. Crest syndrome including anticentromere antibodies and Sjögren's syndrome is more common in elderly patients, while anti- Scl-70 antibodies are more common in younger patients. This suggests the involvement of various mechanisms in the pathogenesis of systemic sclerosis, and that these mechanisms may depend on the age.

The evolution of Raynaud's phenomenon: a longterm prospective study.

OBJECTIVE: To evaluate prospectively a cohort of patients with Raynaud's phenomenon (RP) and signs, symptoms, or laboratory abnormalities suggestive of a connective tissue disease (CTD) to determine prognosis and to identify predictors of evolution. METHODS: Patients with suspected secondary RP were evaluated at baseline, 2.7 years, and 8.4 years after entry by history and examination, chest radiograph and barium esophagram, pulmonary function tests, antinuclear and anticentromere antibodies (ACA), cryoglobulins, and nailfold capillary microscopy (NCM). Logistic regression was used to identify predictors of evolution and to develop a risk factor model. RESULTS: Sixty-four patients were entered and all were subsequently evaluated. Thirty-two (50%) progressed to a definite CTD. Abnormalities of nailfold capillaries [odds ratio (OR) = 21.8] and hand swelling (OR = 18.5) at baseline were independent predictors of the development of systemic sclerosis. A positive ACA was the only risk factor identified for evolution into CREST syndrome (calcinosis, RP, esophageal dysmotility, sclerodactyly, telangiectasias) (OR = 22.5). Finally, nailfold capillary abnormalities were the only baseline feature associated with the development of any definite CTD (OR = 8.3). CONCLUSION: Fifty percent of patients with suspected secondary RP will develop a CTD over a period of 8.4 years. NCM predicts development of systemic sclerosis or any definite CTD and should be included in the evaluation of all such patients.

Improvement of Raynaud's phenomenon after liver transplantation for end-stage primary biliary cirrhosis.

Successful orthotopic liver transplantation may reverse extrahepatic manifestations of the primary chronic liver disease. A well documented improvement of Raynaud's phenomenon, following successful liver transplantation realized for end-stage primary biliary cirrhosis, using repetitive angiological examination and capillary microscopy is presented.

Scleroderma and augmentation mammoplasty--a causal relationship?

BACKGROUND: The studies implicating a causal relationship between silicone and scleroderma, other autoimmune disease, and fibromyalgia-like symptoms have been largely descriptive with absence of appropriate controls and no consideration of potential confounders. This case control study of augmentation mammoplasty and scleroderma represents an attempt to answer these deficiencies. AIMS: To compare the frequency and temporal relationship of augmentation mammoplasty in interviewed and deceased cases and interviewed controls. To determine the frequencies of exposure to non-augmentation mammoplasty silicone, and to determine the frequencies of mastectomy and breast lumpectomy in interviewed cases and controls. METHODS: Scleroderma cases and age-stratified general practice controls were interviewed using a prepilotted telephone questionnaire. Self-reported date/s of augmentation mammoplasty were ascertained, as were dates of onset of first and second scleroderma symptom/s and scleroderma diagnosis, where relevant. Comparison of socioeconomically adjusted rates was expressed in terms of rate ratios. RESULTS: Augmentation mammoplasty rates were comparable between interviewed cases and controls. No augmentation mammoplasty procedures were documented in deceased scleroderma patients' medical records. Rates of exposure to non-mammoplasty silicone, mastectomy and breast lumpectomy were comparable in interviewed cases and controls. CONCLUSIONS: This study failed to demonstrate an association between silicone breast implantation and the subsequent development of scleroderma, to a relative risk level as low as 4.5 with 90% power.