Idiopathic familial chondrocalcinosis due to apatite crystal deposition.

Idiopathic familial chondrocalcinosis was found in five members of a family. The clinical features of the disease were morning stiffness, pain and limitation of motion of the dorsolumbar spine in four of the five members, associated with arthritis of the small joints of the hands in three, shoulder periarthritis in two and costal cartilage pain in one. Radiologically, four of the five patients had multiple intervertebral disk calcifications, mainly located at the nucleus pulposus area. Three of them also had periarticular calcific deposits, associated with costal cartilage calcifications and degenerative changes in the small joints of the hands in two. None of these cases showed cartilage calcification in the knees, public symphysis or triangular ligament of carpus. In the propositus, optical microscopy of a specimen of the second proximal interphalangeal joint obtained by open biopsy showed the presence of multiple calcified areas in the intercellular matrix and chondroid metaplasia with calcification of the matrix in the synovial membrane and capsule. X-ray diffraction studies, energy dispersive analysis, and infrared spectrophotometry of a costal cartilage sample obtained by open biopsy demonstrated the presence of carbonate calcium hydroxyapatite. In this study, no relation was found between HLA antigens, loci A, B and C, and this syndrome due to calcium hydroxyapatite crystal deposition.

[Radiotherapy of cancer of the uterine cervix and successive appearance of new malignant growth in the irradiated field]. / Radioterapia per carcinoma del collo dell'utero e successiva comparsa di nuove neoplasie maligne nel campo di irradiazione.

Among the late complications of high-dosage pelvic radiotherapy for cervical cancer, anorectal and bladder malignancies are sporadically reported in the literature. In this study the possible relationships of previous radiotherapy with late appearance of neoplasms are analyzed and in particular post-radiotherapy interval, dosage and type or irradiation to the cervical area. The mechanisms or neoplastic transformation or irradiated tissues are also studied. Three clinical cases or women irradiated in the past because or cervical cancer and recently treated at our surgical Division for the appearance or four new pelvic malignancies in the irradiated field (three rectal and one bladder cancer are presented. In conclusion, the possible cause-effect relationships between previous radiotherapy and subsequent appearance of neoplasms are analyzed as well as the potential therapeutical consequences or considering these women high-risk subjects. The usefulness or recruiting women with history or previous radiotherapy for cervical cancer in a strict follow-up program (ultrasonography, cytology and endoscopy) is suggested in order to make an early diagnosis of the new pelvic malignancy with a better possibility or treatment.

Familial Hydroxyapatite Chondrocalcinosis with Spondyloepiphyseal Dysplasia: Clinical Course and Absence of Genetic Linkage to the Type II Procollagen Gene.

We describe the course of the articular manifestations in a kindred with familial hydroxyapatite chondrocalcinosis and because of an associated spondyloepiphyseal dysplasia (SED) have investigated the linkage between the disease and markers in the type II procollagen gene (COL2A1). Twenty-seven family members from a large pedigree underwent musculoskeletal and radiographic examinations. In 12 patients, the progression of the disease was evaluated by comparative radiographic surveys obtained 12 years apart. Seven of the 12 family members who were studied in 1978 had severe progression of erosive hand osteoarthritis, whereas there was only minimal progression of the previously observed intervertebral disc or periarticular calcifications. The disease was recognized in seven other siblings from the third generation at a mean age of 24 years. Mild SED was present in several previously and newly diagnosed patients. Nevertheless, no genetic linkage between the disease and COL2A1 polymorphic markers was found. Hydroxyapatite chondrocalcinosis in this kindred displays a variable spectrum of phenotypic manifestations, which include spondyloepiphyseal dysplasia, precocious and progressive erosive hand osteoarthritis, and intervertebral disc and costal cartilage calcification. The gene responsible for the occurrence of hydroxyapatite chondrocalcinosis, osteoarthritis, and mild epiphyseal dysplasia in this family must be one that encodes a protein other than type II procollagen. The mild SED was most easily detected by examining younger affected members. The apatite deposits in this family seem to be secondary to the SED and should be distinguished from those in primary hydroxyapatite disease as in calcific periarthritis.

[Medullary carcinoma of the thyroid. A report of 4 clinical cases and a review of the literature]. / Il carcinoma midollare della tiroide. Presentazione di quattro casi clinici e revisione della letteratura.

Medullary thyroid carcinoma is an uncommon neoplasia among other differentiated carcinomas or the thyroid gland. We have retrospectively analysed four new cases of medullary thyroid carcinoma and a careful review or the literature on the subject has been conducted.

[Clinico-pathological study of microcarcinoma of the thyroid]. / Studio clinico-patologico del microcarcinoma della tiroide.

We have analysed the results of surgical treatment for microcarcinoma of the thyroid (MCT). In sixteen patient clinical and follow-up data were retrospectively evaluated during a 35.1-month follow-up. Thyroid hyperfunctional state us was present in two subjects. A single nodule was detected by echotomography in 11 patients, while multinodular diffuse goitre was revealed in 3 patients. In the last two subjects, thyroid gland appeared completely normal at ultrasonography, despite laterocervical lymph node metastases. Fine-needle aspiration biopsy was performed in 6 patients and its diagnostic accuracy was high (83,3%). MCT was classified as "incidental" in 12 patients and "occult" in the remaining 4 patients. Eight subjects underwent total thyroidectomy and 8 hemithyroidectomy plus isthmectomy. No postoperative complications were recorded. In 10 patients MCT histotype was papillar adenocarcinoma, in 5 was follicular adenocarcinoma and in the remaining case it was medullary carcinoma. Goitre was associated in 75% of the cases. Only in a patient disease progressed to death because of hematogenous metastases. In conclusion, we believe that incidental MCT is a low-grade malignancy with a benign biological behaviour. Occult MCT is a potentially lethal disease. We did not observe differences in the long-term results between different surgical treatments of MCT.

[Role of radioisotopic lymphoscintigraphy in postphlebitic syndrome of the legs]. / Ruolo della linfoscintigrafia radioisotopica nella sindrome postflebitica degli arti inferiori.

Post-phlebitis syndrome of the lower limbs is a set of symptoms that follow a state of phlebostasis and phlebolymphostasis with consequent oedema and tissue distress. We submitted 36 patients with post-phlebitis syndrome of the lower limbs to radioisotopic lymphoscintigraphy for the purposes of evaluating the vicariant function of the lymphatic system and the possible role of the lymphatic system in the genesis of dermo-epidermal abnormalities. The average age of the patients was 53.2 years (range: 43-69 years; M:F ratio: 0.50). The control group consisted of 6 healthy subjects. The average duration of the post-phlebitis syndrome in the patients studied was 8.5 years. We excluded from the study patients in whom a central cause was identified as being responsible for the pathogenisis of the oedema of the lower limbs. In addition, patients with obliterant arteriopathy were also excluded. Venous pathology was evaluated first clinically and then investigated by continuous-wave Doppler. As a first step, venous pressure was measured by Doppler phlebomanometry in clino- and orthostatism. All patients underwent radioisotopic lymphoscintigraphy with microcolloids using the Rijke technique. Radioactivity was monitored by means of a computerized gamma-camera. We classified the pathological findings of radioisotopic lymphoscintigraphy as follows: 1) delayed transit; 2) obstacles; 3) star-shaped superficial collateral lymphatic circulations; 4) lymphocoele or cutaneous lakes. A significant difference was detected (p < 0.05) between the pressure values in the post- phlebitis lower limbs and the pressure values in normal subjects. Combining the results of our measurements we recorded delayed transit in 5 patients (69.5%). This latter group included the cases with the severest forms of post-phlebitis syndrome. Therefore, better knowledge of the pathophysiology of the lymphatic system would appear to be useful in order to understand the origin and evolution of oedema of the lower limbs of patients with post-phlebitis syndrome. To this end, radioisotopic lymphoscintigraphy may be useful as a first-level examination in order to evaluate the capacity and efficiency of the lymphatic system.

[Hürthle cell neoplasms of the thyroid gland]. / Le neoplasie della tiroide a cellule di Hürthle.

From 1986 to 1996 the Authors have surgically treated 34 patients affected with Hürthle cell neoplasm of the thyroid (23 benign and 11 malignant). Preoperative diagnosis was obtained mainly by fine needle aspiration biopsy. In thyroid surgery we routinely prepare laryngeal nerve and take great care to avoid devascularization fo the parathyroid glands. Operative procedures performed were hemithyroidectomy plus isthmectomy (18), subtotal thyroidectomy (2) and total thyroidectomy (14). No cervical lymph node dissection was requested, neither we observed post-operative morbidity. Mean follow-up was 116 months. During observation period we documented. No hematogenous metastasis was observed. All patients are now well and alive free of disease. This series stresses the favourable behavior of Hürthle cell neoplasm of the thyroid--even through a prolonged follow-up. A thorough review of the Literature on the topic is conducted. The Authors are in favour of total thyroidectomy as first choice procedure for lesions larger than 40 mm in order to reduce the need of completion thyroidectomy and the potential morbidity.

Emergencias y urgencias en reumatología clínica / Urgencies and emergencies in clinical rheumatology

En la presente revisión se analizan los casos de urgencias y Emergencias en Reumatología y Enfermedades Autoinmunes Sistémicas del adulto y juveniles; las mismas son situaciones que requieren asistencia médica inmediata. Además se mencionan las complicaciones agudas que surgen de las mismas (infección, desorden metabólico, insuficiencia de órgano) y las reacciones adversas que pueden surgir de los tratamientos efectuados. Se destacan las patologías por órgano o sistema y luego por síndrome o enfermedad. La revisión tiene la intención de ser de ayuda al médico joven para un rápido reconocimiento, diagnóstico y tratamiento de las patologías agudas y sus complicaciones en la reumatología actual

Tratamiento de la artritis psoriásica con ustekinumab en diferentes escenarios clínicos. Casos reales y revisión de la literatura / Treatment of psoriatic arthritis with ustekinumab in different clinical scenarios. Real cases anda literature review

El tratamiento de la Artritis Psoriásica (APs) se basa en suprimir los signos y síntomas en todos los componentes de la enfermedad (articular, piel, entesis, compromiso axial). Dentro de las opciones terapéuticas contamos con los antinflamatorios no esteroideos (AI-NEs), corticoides, drogas modificadoras de la enfermedad (DMARs) entre ellas el metotrexato y leflunomida, y los anti-TNF. Estas últimas han demostrado actualmente amplia eficacia a largo plazo y buen perfil de seguridad. Fueron el único mecanismo de acción para el tratamiento de la APs; sin embargo en el último año fue aprobado en varios países, ustekinumab, un inhibidor de la subunidad p40 de la IL12 y 23. Esta revisión presenta una serie de 6 casos clínicos donde hemos utilizado esta opción terapéutica en diferentes escenarios

Estrategia para la derivación oportuna: experiencia en un centro de referencia en reumatología / Strategy for temely referral: experience in a reference center in rheumatology

Introducción: En los últimos años se ha reconocido la importancia del diagnóstico precoz de la artritis reumatoidea y las espondiloartritis. Aún existen barreras que impiden la derivación precoz de estos pacientes. Objetivo: Evaluar si existe un aumento significativo en el número de derivaciones al Servicio de Reumatología luego de implementar una estrategia de concientización a otros especialistas. Material y métodos: Estudio observacional, retrospectivo. Resultados: Durante el primer período, el servicio realizó un total de 1027 consultas, de las cuales 130 fueron derivaciones. Las consultas efectuadas luego de la implementación del plan de derivación fueron 1199 con 202 derivaciones (17% IC 95 14,7-19); la diferencia entre ambos períodos fue estadísticamente significativa (p 0,003). Conclusión: La implementación de estrategias de derivación fue valiosa, puesto que encontramos un incremento en el número de derivaciones realizadas. Consideramos que estas intervenciones deben perdurar en el tiempo para mejorar el diagnóstico precoz.

Introduction: In recent years, the importance of early diagnosisof rheumatoid arthritis and spondyloarthritis has been recognized. However, there are still barriers that obstruct the early referral ofthese patients. Objective: To evaluate whether there is a significant increase in thenumber of referrals to the department of Rheumatology after implementinga strategy of awareness to other specialists. Material and methods: Observational and retrospective study. Results: During the first period, the service conducted a total of1027 consultations, of which 130 were referrals. Consultations made after the implementation of the derivation strategy were 1199 of which 202 were referrals (17% CI 95 14.7-19); the difference between the two periods was statistically significant (p 0.003). Conclusion: The implementation of this strategy was valuable, since we found an increase in the number of referrals made. Weconsider that these interventions should last over time to improveearly diagnosis.

Tocilizumab en artritis psoriásica ante la falla a los bloqueantes del factor de necrosis tumoral alfa: experiencia en dos casos / Tocilizumab in psoriatic artritis in patients falling anti-tumor necrosis factor: experience in two cases

En artritis psoriásica (APs), los bloqueantes del factor de necrosis tumoral alfa (anti-TNF) son la opción más adecuada ante la falla a drogas modificadoras. La eficacia y la seguridad de los anti-TNF están ampliamente fundamentadas en la literatura; sin embargo, en algunos casos, pueden presentarse eventos adversos o no se logra la eficacia deseada. Las alternativas terapéuticas en dichos pacientes son acotadas, la inhibición de la interleuquina 6 (IL-6) podría ser una opción. Presentamos dos casos clínicos de pacientes con APs resistentes a anti-TNF que recibieron tocilizumab, en los cuales podemos observar diferencias importantes en el perfil de eficacia de esta droga

In psoriatic arthritis, the blocking of tumor necrosis factor alpha (anti-TNF) is the most suitable option when modifying antirheumatic drugsfail. The efficacy and safety of anti-TNF are largely supported by theliterature; however, in some cases, adverse events may occur or thedesired efficiency is not achieved. Therapeutic alternatives in thesepatients are bounded; inhibition of interleukin 6 could be an option.We present two cases of patients with resistant anti-TNF receivingtocilizumab, in which we can observe significant differences in theefficacy profile of the drug.

Monoterapia biológica en pacientes con artritis reumatoidea en Argentina / Biological monotherapy in patients with rheumatoid arthritis in Argentina

Introducción: La utilización de agentes biológicos para el tratamiento de la Artritis Reumatoidea (AR) es habitualmente usada en aquellos pacientes con enfermedad activa que no hayan respondido al tratamiento con drogas modificadoras de la Artritis Reumatoidea convencionales (DMARD, por sus siglas en inglés) o que hayan presentado intolerancia a las mismas. Al estado actual de la evidencia, la terapia combinada de agentes biológicos más un DMARD convencional (principalmente metotrexato) constituye el estándar de tratamiento. Sin embargo existen algunos escenarios como la intolerancia, la falta de adherencia y la aparición de eventos adversos a las DMARDs convencionales donde la monoterapia biológica emerge como una opción terapéutica válida. Según los distintos registros a nivel internacional, la frecuencia de utilización de agentes biológicos en monoterapia oscila entre 12 a 39%. Debido a la ausencia de estos datos a nivel local decidimos realizar este estudio para conocer el porcentaje de pacientes que se encuentran en monoterapia biológica y analizar las causas que llevaron a este tipo de tratamiento. Materiales y métodos: Estudio de tipo corte transversal donde se invitó a participar a diferentes centros reumatológicos distribuidos a lo largo de Argentina. Cada centro revisó las historias clínicas de los últimos 30 a 50 pacientes consecutivos vistos con AR, mayores de 18 años, que habían presentado inadecuada respuesta al tratamiento con DMARDs y que estaban bajo tratamiento biológico. Se completaba una ficha por cada paciente incluido, registrando datos demográficos, de la enfermedad y tratamientos previos. Resultados: Se incluyeron 32 centros y se evaluaron 1148 historias clínicas de pacientes con AR durante el mes de octubre y noviembre del 2012. Un 21,4% (246) de los pacientes al momento del estudio se encontraba bajo tratamiento biológico en monoterapia...

Introduction: The use of biological agents for the treatment of rheumatoid arthritis (RA) is commonly used in patients with active disease who have not responded to treatment with conventional rheumatoid arthritis-modifying drugs (DMARDs) or Who have presented intolerance to them. At the present state of evidence, combined therapy of biological agents plus conventional DMARD (mainly methotrexate) is the standard of treatment. However, there are some scenarios such as intolerance, lack of adherence and the appearance of adverse events to conventional DMARDs where biological monotherapy emerges as a valid therapeutic option. According to different international registries, the frequency of use of biological agents in monotherapy ranges from 12 to 39%. Due to the absence of these data at the local level we decided to carry out this study to know the percentage of patients who are in biological monotherapy and to analyze the causes that led to this type of treatment. Materials and methods: A cross-sectional study where different rheumatologic centers throughout Argentina were invited to participate. Each center reviewed the medical records of the last 30 to 50 consecutive patients seen with RA, older than 18 years, who had inadequate response to treatment with DMARDs and who were under biological treatment. One card was completed for each patient included, recording demographic, disease and previous treatment data. Results: Thirty-two centers were included and 1148 clinical records of patients with RA were evaluated during October and November 2012. A total of 244 patients (246) at the time of the study were under monotherapy...

Male systemic lupus erythematosus in a Latin-American inception cohort of 1214 patients.

The objective of the study was to evaluate the influence of the male gender in the clinical presentation and outcome of systemic lupus erythematosus in a prospective inception cohort of Latin-American patients. Of the 1214 SLE patients included in the GLADEL cohort, 123 were male. Demographic characteristics as well as clinical manifestations, laboratory profile, activity and damage scores were evaluated at onset and during the course of the disease and compared with female patients. The median age at onset of the male patients was 27 and that at diagnosis 29.2 years. Delay to diagnosis was shorter in males (134 versus 185 days, P = 0.01). At onset, men more frequently showed fever (42.3 versus 27.0%, P = 0.001) and weight loss (23.6 versus 11.8%, P = 0.001). During disease course the incident of symptoms was: fever, 67.8 versus 55.6%, P = 0.012; weight loss, 47.2 versus 24.3%, P = 0.001; arterial hypertension, 37.4 versus 25.8%, P = 0.007; renal disease (persistent proteinuria and/or cellular casts), 58.5 versus 44.6%, P = 0.004); and hemolytic anemia, 19.5 versus 10.9%, P = 0.008. The laboratory results showed that: men more frequently had IgG anticardiolipin antibodies (68.2 versus 49%, P = 0.02) and low C3 (61.3 versus 48.1%, P = 0.03); 5/123 men died (4%) compared with 29/1091 women (2.7%). In conclusion, 10% of GLADEL's cohort patients were male. They showed a distinctive profile with shorter delay to diagnosis, higher incidence of fever, weight loss, arterial hypertension, renal disease, hemolytic anemia, IgG anticardiolipin antibodies and low C3. Although not statistically significant, mortality was higher in men.

Laxity and rupture of the patellar tendon in systemic lupus erythematosus. Association with secondary hyperparathyroidism.

We describe a patient with systemic lupus erythematosus, chronic renal failure and secondary hyperparathyroidism who developed laxity and elongation of the patellar tendon, followed by its rupture one year later. Hydroxyapatite and urate crystals were identified from the chalky material surrounding the patellar tendon observed at surgery. These findings suggest that tendon laxity and elongation could possibly be detected before its rupture and that secondary hyperparathyroidism could be considered as another causative factor of tendon damage in patients with systemic lupus erythematosus.

Atlantoaxial subluxation in systemic lupus erythematosus: further evidence of tendinous alterations.

We prospectively determined the frequency of atlantoaxial subluxation in a group of patients with systemic lupus erythematosus (SLE) and analyzed its relationship with tendinous laxity, Jaccoud's syndrome and other features of the disease. Five of 59 patients (8.5%) had atlantoaxial subluxation. No patient presented atlantoaxial subluxation in neutral lateral cervical radiographs but all 5 had anterior atlantoaxial subluxation in full flexion films; one patient also had lateral subluxation. The 5 patients with atlantoaxial subluxation were compared with the remaining 54. Mean SLE disease duration was longer in patients with atlantoaxial subluxation (12 years) than in those without (6.6 years) (p less than 0.01). Jaccoud's syndrome, patellar tendon elongation and articular hypermobility were significantly more frequent in patients with atlantoaxial subluxation. The presence or history of arthritis failed to distinguish patients with and without atlantoaxial subluxation, while chronic renal failure and increased serum parathyroid hormone levels were significantly associated to the presence of atlantoaxial subluxation. We suggest that atlantoaxial subluxation is further evidence of tendinous alterations seen in patients with SLE.

Effect of antimalarial treatment on circulating immune complexes in rheumatoid arthritis.

The relationship between the effect of chloroquine treatment on circulating immune complexes in patients with rheumatoid arthritis (RA) was determined by the 125I Clq binding assay. Three groups were studied: (a) 20 patients treated daily for 6 months with chloroquine sulphate 250 mg plus prednisone 7.5 mg and nonsteroidal antiinflammatory drugs (NSAID); (b) 20 patients not taking antimalarials but treated with prednisone and NSAID; (c) 41 controls. Results suggest that chloroquine sulphate therapy induced a marked decrease of immune complexes in patients with RA, an effect not observed with treatment by prednisone and NSAID only.

Analysis of molecular heterogeneity of prolactin in human systemic lupus erythematosus.

Hyperprolactinemia without clinical manifestations has been reported in some patients with systemic lupus erythematosus (SLE) because an increase of prolactin (PRL) is produced due to the BIG/BIG molecular variant (molecular variant < 150 kD). This research project aimed to determine levels of PRL: its bioactive form, the little nonglycosylated form (NGPRL) and variants with decreased bioactivity such as the BIG/BIG and the little glycosylated (GPRL), in 29 women and five men with SLE. PRL was assayed by IRMA with a kit from Immunotech Laboratory, the BIG/BIG form by precipitation with polyethyleneglycol 6000, and the NGPRL and GPRL by chromatography on Concanavalin-A- Sepharose. Increased PRL was detected in seven patients (20.6%) of whom three had increased BIG/BIG, six had increased GPRL and only four had increased NGPRL. The three cases with increased BIG/BIG were contrasted by chromatography on Sephadex G-100. No increased PRL or any of the other variants assayed were found in men. Results were similar when PRL was evaluated in the same blood samples by a different IRMA (DPC Laboratory). The etiology of the hyperprolactinemia in some of these patients is unknown, but their lack of symptoms (galactorrhea or amenorrhea) could be due to the BIG/BIG forms and basically to the glycosylation of the hormone. As for the relation between PRL and SLE activity, we found that hyperprolactinemic patients were younger, had a shorter history of illness, although it was not statistically significant, and a higher SLEDAI score. This would indicate a relation between hyperprolactinemia and lupus activity. The patients with increased BIG/BIG form also had a very active illness at the time of the study.

Tendinous laxity and Jaccoud's syndrome in patients with systemic lupus erythematosus. Possible role of secondary hyperparathyroidism.

Fourteen of 52 unselected patients with systemic lupus erythematosus (SLE) (27%) had ligamentous derangement demonstrated by either Jaccoud's syndrome and/or patellar tendon elongation. Three cases had only Jaccoud's syndrome, 4 isolated patellar tendinous laxity, while the remaining 7 presented both findings. Jaccoud's syndrome and/or tendinous laxity were not associated to an increased frequency of arthritis, corticosteroid therapy or a longer disease duration, but significantly associated with increased serum PTH levels secondary to chronic renal failure. Hyperparathyroidism secondary to chronic renal failure should, therefore, be considered a potential factor contributing to the development of Jaccoud's syndrome and/or tendinous laxity in patients with SLE.