Enfermedades osteocondensantes con compromiso de huesos largos: presentación de dos casos y revisión de la literatura / Sclerosing bone diseases with involvement of long bones: report of two cases and literature review

Las enfermedades osteocondensantes son un grupo de patologías poco frecuentes que se caracterizan por aumento de la masa ósea, comprometiendo tanto a huesos largos como a huesos planos. Tradicionalmente, la radiología simple ha permitido su diagnóstico al identificar patrones de afectación ósea característicos de cada enfermedad. Actualmente, la caracterización molecular y genética ha facilitado la comprensión del sustrato fisiopatológico y la expresión fenotípica de estás patologías, sin embargo, la radiología simple continua teniendo un valor inconmesurable en el reconocimiento de las enfermedades osteocondensantes.

Sclerosing bone disorders are a rare group of diseases characterized by increased bone mass in both long and flat bones. Traditionally, plain radiography has allowed the diagnosis of these diseases identifying characteristic patterns of bone involvement. At present, the molecular and genetic characterization of these diseases has provided a better understand of their pathophysiology and phenotypic expression, however plain radiography continues to have an important role in the recognition of sclerosing bone disorders.

Historia de la Artritis Psoriática. Primera parte. Desde Alibert hasta V. Wright / History of Psoriatic Arthritis. First part. From Alibert to V. Wright

Presentamos, en esta primera parte de la historia de la artritis psoriática, los eventos que llevaron al conocimiento de esta enfermedad, de cómo se separó de las otras y cómo se generaron los primeros criterios clasificatorios de esta patología.Palabras clave: historia, espondioartropatía, psoriasis, artritis psoriática.

In this first part of the history of psoriatic arthritis, we present the most important events that led to the knowledge of this disease, how it was separated from other inflammatory arthropathies, as well as how the first classificatory criteria in this disease were developed.Key words: history, spondyloarthropathy, psoriasis, psoriatic arthritis.

Vasculitis linfomonocítica primaria de inicio tardío, estrictamente de nervio periférico / Primary Lymphocytic Vasculitis of late onset, Limited to the Peripheral Nerve

En este artículo presentamos los hallazgos de vasculitis estrictamente de nervio periférico en seis pacientes. Los hallazgos corresponden a una vasculitis que ocasiona una polineuropatía sensitivo-distal en guantes y medias cuyo infiltrado es de tipo linfo-monocítico, ausencia de necrosis fibrinoide, con un buen pronóstico, pocas recaídas y buena respuesta al tratamiento. Planteamos que esta patología debe tenerse en cuenta en el diagnóstico diferencial de las polineuropatías y mononeuritis múltiple. Se hace una revisión de la literatura.

We present the finding of strictly peripheral nerve vascultis in six cases. The finding are secondary to a vasculitis that produce a stocking-glove sensitive-motor polyneuropathy, with an limphomonocytic infiltrate, absence of fibrinoid necrosis, good prognosis, low recurrences and an excellent response to treatment. We propose that this condition should be considered in the differential diagnosis of polyneuropathies and multiplex mononeuritis. A literature review is made.

Paniculitis y eritema nodoso. Un estudio de correlación clínico-biológica / Panniculitis and erythema nodosum. A clinical and biological correlation

Objetivos: el propósito de este estudio fue analizar la frecuencia de presentación de la paniculitis en nuestro medio, valorar su presentación clínica, factores etiológicos, las manifestaciones histológicas típicas en el grupo de pacientes con eritema nodoso clasificándolas en los diferentes estadios y su correlación con los hallazgos de los subgrupos celulares predominantes en cada una de las etapas de la enfermedad. Materiales y métodos: se incluyeron 60 pacientes con diagnóstico de paniculitis, valorados de manera prospectiva en nuestro servicio en el período comprendido entre junio de 1994 y junio de 1998. Se realizó una historia y examen físico completo y se evaluaron factores de riesgo. Se realizaron estudios paraclínicos complementarios. Se estableció una clasificación de las lesiones, de acuerdo a su estadio histológico, dependiendo del tipo celular predominante y alteraciones tisulares, en lesiones tempranas (incipientes), establecidas (activas) y tardías. Se realizó estudio histológico con tinción hematoxilina eosina a un subgrupo de 26 pacientes con diagnóstico clínico de eritema nodoso. Se estudiaron con anticuerpos monoclonales (ACL, CD15, CD45Ro, CD45Ra, CD68, CD35, DR, DP, DQ, CD4 y CD8) las 26 muestras para determinar la presencia o ausencia de leucocitos en las lesiones y los subtipos celulares más frecuentes (Linfocitos T, linfocitos B, granulocitos, células presentadoras de antígeno, macrófagos). Se estableció una correlación entre los hallazgos clínicos, histológicos y de inmunohistoquímica, de acuerdo al estadio de las lesiones. Resultados: 92% (n=55) de los pacientes eran mujeres; la edad promedio de presentación de la enfermedad fue de 34 años. El tipo de lesión más frecuentemente observada fue el nódulo en el 83% de los pacientes (n=50). El sitio de presentación más frecuente fue en la pierna en el 77% de los pacientes (n=46), acompañándose de dolor en la lesión en el 87% (n=52). La velocidad de sedimentación y la proteína C reactiva fueron positivas en la mayoría de los pacientes. La patología más frecuentemente asociada fue la faringoamigdalitis en 17% de los pacientes (n=10) y no se encontraron patologías asociadas en el 25% de los casos (n=15). De los 26 estudios histológicos dos correspondieron a vasculitis nodular (8%), el 23% (n=6) se encontraban en un estadio inicial de eritema nodoso, el 46% (n=12) de las lesiones se encontraban en un estadio activo bien desarrollado. El 23% (n=6) de las lesiones se encontraba en un estadio tardío de regresión. Por técnicas de inmunohistoquímica se encontraron linfocitos (antígeno Común leucocitario) en el 100% de los casos (n=26)). En las lesiones tempranas se encontraron principalmente células presentadoras de antígeno (DR, DP, DQ, CD35) y linfocitos T (CD45Ro); en las lesiones activas se encontraron predominantemente linfocitos T (CD45R0), seguidos por células presentadoras de antígeno (DR, DP, DQ, CD35) y macrófagos (CD 68). En las lesiones tardías se encontraron linfocitos T (CD45Ro). En las dos muestras con hallazgo de vasculitis nodular los granulocitos (CD15) fueron más frecuentes. Conclusiones: el Eritema Nodoso es una enfermedad frecuente dentro del grupo de pacientes con paniculitis, presentándose principalmente en mujeres y de características idiopáticas en el 25% de los pacientes. La enfermedad se presenta en diferentes estadios clínicos e histológicos. En el estadio inicial predominan las células presentadoras de antígeno (DR, DP, DQ, CD35) y los linfocitos T (CD45Ro); en el estadio activo (lesiones bien desarrolladas) predominan los linfocitos T (CD45R0), seguidos por células presentadoras de antígeno (DR, DP, DQ, CD35) y macrófagos (CD 68). En el estadio tardío (en regresión) predominan los linfocitos T (CD45Ro ). Es una enfermedad cutánea por hipersensibilidad celular, dependiente de células T, posiblemente células CD4. En la vasculitis nodular llama la atención que predominan los granulocitos (CD15), sin observarse predominancia de células presentadoras de antígenos ni linfocitos T, por lo cual inferimos que son patologías totalmente diferentes en su patogénesis.

Objective: to assess the frequency, etiologic factors, clinical patterns, histological types of panniculitis, and to correlate the different histologic patterns with stages of the disease. Material and methods: this is a prospective study of 60 patients with the diagnosis of panniculitis referred to our service between June 1994 and June 1998. A complete history and physical examination was performed, risk factors were evaluated. Laboratory studies were performed. A classification of the lesions depending on the predominant cellular type and tissue alterations were done, in early (incipient), established (active) and delayed injuries. Biopsy of the lesion and H&E examination was done in 26 patients. In addition, immunohistochemical analysis was performed using the following monoclonal antibodies (LCA, CD15, CD45Ro, CD45Ra, CD68, CD35, DR, DP, DQ, CD4 and CD8) to determine the presence or absence of leukocytes, and cellular subtypes including lymphocytes, T and B, polymorphonuclear, dendritic cells, and macrophages. A correlation between the clinical, histological and inmmunohistochemical findings, according to the stage of the lesions were established. Results: the majority of patients were women-55 (92%), mean age was 34 years. Nodular lesions were the most common - seen in 50/60 (83%), with lower extremities most commonly affected - 46/60 (77%). Most lesions were painful - 52/60 (87%). Both ESR and CRP were elevated in most patients. A precipitating event was present in 75%. Tonsillitis was present in 10/60 (17%). One-fourth (n=15) of patients did not exhibit clinical associated pathology. Of the 26 studies realized, histologically vasculitis was found in 2 cases, 6 cases were deemed to be in early stages of EN (23%), 12 (46%) were well developed active EN, and 6 (23%) exhibited late stage and in regression. Immunohistochemical analysis revealed: lymphocytes present in all cases. In early stages APC (DR, DP, DQ, CD35) and CD45Ro were the dominant types; in active lesions CD45Ro and to a lesser degree APC and macrophages (CD68) were the predominant cell types. In late stages CD45Ro lymphocytes were the dominant cell types. In the 2 cases with nodular vasculitis - CD15 PMN cells were the most frequent. Conclusion: erythema nodosum is a relatively frequent condition, most commonly seen in women, and of unknown etiology in 25% of cases. The diseases is presented in different clinical and histological stages. In early stages, APC and CD45Ro lymphocytes predominate, while in late stages CD45Ro T lymphocytes are the predominant cell type. In active and well developed stages, CD45Ro, APC and CD68 cells predominate. PMN (CD 15) appears to be the dominant cell type in the nodular vasculitic variant, with no predominance of neither APC o T lymphocytes, thus we inferred that they are totally different pathologies in its pathogenesis.

Fine mapping of 10q and 18q for familial Alzheimer's disease in Caribbean Hispanics.

Familial Alzheimer's disease (AD [MIM 104300]) has been a focus of intense investigation, primarily in Caucasian families from Europe and North America families. Although the late-onset form of familial AD, beginning after age 65 years, has been linked to regions on chromosomes 10q and 12p, the specific genetic variants have not yet been consistently identified. Using a unique cohort of families of Caribbean Hispanics ancestry, we screened the genome using 340 markers on 490 family members from 96 families with predominantly late-onset AD. We observed the strongest support for linkage on 18q (LOD=3.14). However, 17 additional markers (chromosomes 1-6, 8, 10, 12, and 14) exceeded a two-point LOD score of 1.0 under the affecteds-only autosomal dominant model or affected sibpair model. As we previously reported the fine-mapping effort on 12p showing modest evidence of linkage, we focused our fine-mapping efforts on two other candidate regions in the current report, namely 10q and 18q. We added 31 family members and eight additional Caribbean Hispanic families to fine map 10q and 18q. With additional microsatellite markers, the evidence for linkage for 18q strengthened near 112 cM, where the two-point LOD score for D18S541 was 3.37 and the highest NPL score in that region was 3.65 (P=0.000177). This narrow region contains a small number of genes expressed in the brain. However, at 10q (134-138 cM), the NPL score decreased from 3.15 (P=0.000486) to 2.1 (P=0.0218), but two broad peaks remained overlapping with previously reported peaks. Our results provide modest support for linkage on 10q and 12p in this cohort of Caribbean Hispanic families with familial Alzheimer's disease, and strong evidence for a new locus on 18q.

Chromosome-12 mapping of late-onset Alzheimer disease among Caribbean Hispanics.

Linkage to chromosome 12p for familial Alzheimer disease (AD) has been inconsistent. Using 35 markers near the centromere of chromosome 12, we investigated 79 Caribbean Hispanic families with AD. Two-point linkage analysis using affected sib pairs yielded LOD scores of 3.15 at D12S1623 and 1.43 at D12S1042. The LOD score at D12S1623 decreased to 1.62 in families with late-onset (age >65 years) AD (LOAD), but the LOD score at D12S1042 was unchanged. Among families negative for the apolipoprotein E (APOE-epsilon 4) allele, the LOD score for D12S1623 was lower (1.01), whereas that for D12S1042 increased to 1.73. Among families positive for the APOE-epsilon 4 allele, none of the LOD scores reached 1. Multipoint affected-relative-pair analysis showed peaks at D12S1623 (nonparametric linkage [NPL] score 1.52; P=.028) and near D12S1042, at D12S1057 (NPL score 1.57; P=.027). NPL scores for both D12S1623 and D12S1057 increased in families affected with LOAD, but, in APOE-epsilon 4-negative families, only scores for the region flanking D12S1623 remained elevated (NPL score 1.74; P=.013). This study of Caribbean Hispanics with familial AD extends and provides modest evidence of linkage to loci on chromosome 12p. Linkage varied by age at onset of AD and by the presence or absence of the APOE-epsilon 4 allele.

A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families.

CONTEXT: Genetic determinants of Alzheimer disease (AD) have not been comprehensively examined in Caribbean Hispanics, a population in the United States in whom the frequency of AD is higher compared with non-Hispanic whites. OBJECTIVE: To identify variant alleles in genes related to familial early-onset AD among Caribbean Hispanics. DESIGN AND SETTING: Family-based case series conducted in 1998-2001 at an AD research center in New York, NY, and clinics in the Dominican Republic. PATIENTS: Among 206 Caribbean Hispanic families with 2 or more living members with AD who were identified, 19 (9.2%) had at least 1 individual with onset of AD before the age of 55 years. MAIN OUTCOME MEASURE: The entire coding region of the presenilin 1 gene and exons 16 and 17 of the amyloid precursor protein gene were sequenced in probands from the 19 families and their living relatives. RESULTS: A G-to-C nucleotide change resulting in a glycine-alanine amino acid substitution at codon 206 (Gly206Ala) in exon 7 of presenilin 1 was observed in 23 individuals from 8 (42%) of the 19 families. A Caribbean Hispanic individual with the Gly206Ala mutation and early-onset familial disease was also found by sequencing the corresponding genes of 319 unrelated individuals in New York City. The Gly206Ala mutation was not found in public genetic databases but was reported in 5 individuals from 4 Hispanic families with AD referred for genetic testing. None of the members of these families were related to one another, yet all carriers of the Gly206Ala mutation tested shared a variant allele at 2 nearby microsatellite polymorphisms, indicating a common ancestor. No mutations were found in the amyloid precursor protein gene. CONCLUSIONS: The Gly206Ala mutation was found in 8 of 19 unrelated Caribbean Hispanic families with early-onset familial AD. This genetic change may be a prevalent cause of early-onset familial AD in the Caribbean Hispanic population.