[Crohn s disease: is still the reason of fever of unknown origin?]. / Enfermedad de Crohn: ¿todavía hoy causa de fiebre de origen desconocido clásica?

We present two patients with Crohn's disease who presented with fever unknown origin, and mild intestinal symptoms. In case 1, the debut was with intermittent fever and symmetrical polyarthritis of the wrists, elbows, ankles and knees; in the case 2, prolonged fever associated to unspecific colicky abdominal pain. The initial approach was fever unknown origin yielded no etiology in both of them. The barium studies of the intestinal tract of paramount importance to reach a positive diagnosis in both cases. We strongly recommend the use of barium studies as a first line diagnostic tool in the approach of fever unknown origin.

[Nonalcoholic steatohepatitis, the enigma of bad progression]. / Esteatohepatitis no alcohólica, el enigma de una mala evolucion.

Still, very little is known about the precise pathogenetic mechanisms, the triggering events and in particular, the evolution and treatment of nonalcoholic steatohepatitis (NASH). It is part of the broad spectrum of nonalcoholic fatty liver diseases (NAFLDs). Mainly, it has been reported as a benign disease, associated with metabolic disorders commonly occurrence en the general population. Nevertheless, the syndrome can lead to cirrhosis, liver failure or hepatocellular carcinoma, requiring liver transplantation. We present one patient with diagnosis of NASH, who was treated initially for overweight, HTA and hyperlipaemia with incompleted response and who showed a quickly progress to cirrhosis but no cause of liver decompensated disease could be identified. Currently she is at end-stage waiting a liver transplantation. Controlled and multicentric studies with the same definition of NASH and the study end-points are needed, and will provide information about diagnosis features and novel therapies to early management of the disease.

Computed tomography findings of peritoneal tuberculosis: systematic review of seven patients diagnosed in 6 years (1996-2001).

OBJECTIVE: The aim of this study was to describe the computed tomography (CT) findings in patients with demonstrated peritoneal tuberculosis (TB) and their concordance with the three types from the traditional classification (wet, fibrotic, and dry plastic). METHODS: We reviewed the CT images of all patients with microbiologically proven peritoneal tuberculosis over a 6-year period (1996-2001). RESULTS: Seven patients were included. Ascites was present in 5 patients (free ascites in 3 patients and loculated in 2). Involvement of the mesentery was found in 5 patients, the omentum in 4, and the parietal peritoneum in 3. Tuberculous lymphadenitis was the most common associated finding (6 patients). Two patients had hepatic lesions. The fibrotic type was found in all the patients, and 5 patients had an association of the fibrotic and wet types. None of the patients had lesions consistent with the dry plastic type. CONCLUSION: Peritoneal tuberculosis is best described as a combination of ascites, peritoneal lesions, and lymphadenopathy, rather than the three types from the traditional classification.

[Scleroderma with traces of disseminated lupus erythematosus associated with Hashimoto's thyroiditis and papillary carcinoma of the thyroid gland (author's transl)]. / Esclerodermia con rasgos de lupus eritematoso diseminado (conectivopatía de superposición), asociada a tiroiditis de Hashimoto y carcinoma papilar de tiroides.

The coexistence of organ-specific and nonorgan-specific autoimmune diseases is an interesting phenomenon. A 52-year-old woman was admitted with fever, general discomfort, polyarthritis, and Raynaud's phenomenon. Physical examination revealed a goiter of stony consistency, hardening, paleness, and atrophy of the skin on the face and upper limbs, and blood hypertension (180/110 mmHg). The biological data included leukopenia, moderate anemia, and a very high sedimentation rate. The latex test was positive (+++); LE cells positive (+); hypergammaglobulinemia (3.5 g); antinuclear antibodies, 1/1280 with an immunofluorescence granular pattern; antithyroid antibodies, 1/160. There was pulmonary, renal, and gastrointestinal involvement compatible with scleroderma, which was confirmed by skin biopsy. A thyroidectomy revealed the existence of a papillary carcinoma with thyroiditis. Responde to treatment with immunosuppressive agents, hypotensive drugs, and thyroid substitution therapy was initially good. The patient was readmitted 8 months later with general discomfort and a severe hyperproteinemia (10 g/100 ml), including 65 percent gammaglobulin and requiring various sessions of plasmapheresis. The patient was discharged, but died suddenly 4 months later. The association of lupus and scleroderma in this patient is discussed and the possibility of its being a mixed connective tissue disease is discarded. The association of this condition with Hashimoto's thyroiditis, and the latter with papillary carcinoma of the thyroid are analyzed. The peculiar features of this case are pointed out. The authors postulate that the cause of the sudden death was a vascular cerebral complication induced by the extreme hyperproteinemia.

[Waldenström's macroglobulinemia, cryoglobulinemia type I and membranous glomerulonephritis]. / Macroglobulinemia de Waldenström, crioglobulinemia tipo I y glomerulonefritis membranosa.

Renal complications in Waldenström's macroglobulinemia (WM) are infrequent and are characterized by the presence of PAS positive amorphous hyaline deposits in the capillary lumen, infiltrated with lymphoplasmatic cells with PAS positive inclusions in the interstices and intratubular hyaline cylinders. Membranous glomerulonephritis may be a paraneoplastic manifestation of the lymphoproliferative processes. A 67-year-old male was diagnosed of WM, type-I cryoglobulinemia with renal insufficiency without proteinuria. Renal histological examination revealed changes characteristic of nephropathy associated to WM as well as membranous glomerulonephritis. This association has not been described previously. The coexistence of two pathogenic mechanisms with a common base, lymphoproliferative disease, may explain this association.

[Platelet function in systemic lupus erythematosus (author's transl)]. / Estudio de la función plaquetaria en el lupus eritematoso sistémico (LES).

The platelet function was studied in 23 patients with systemic lupus erythematosus, all of whom met the diagnostic creteria established by the American Rheumatism Association. They were not under any treatment, especially with any drug that might interfere with platelet function. The same study was performed on a control group composed of volunteers donors at a blood bank. The platelet count was definitely lower in the patients with lupus than in the control subjects (p less than 0.0005), although a clear thrombopenia was observed in only two indivduals (8.7 percent). Anti-platelet antibodies were found in only six cases (26 percent). There was a linear correlation between thrombopenia and the presence of hemorrhagic diathesis and low levels of C4 and CH50 components. Plateler adhesiveness was clearly lower in the lupus group than in the control group (p less than 0.0005). The presence of kidney disease determined a greater impairment of the platelet adhesiveness (p less than 0.0025). A notable defect on platelet aggregation was induced by ADP, adrenaline and collagen. This was more apparent in the group of patients exhibiting a higher degree of clinical activity and in those who showed a serum complement decrease. The mechanism responsible for this thrombopathy appears to be an interference in the platelet function due to the presence of circulating immunocomplexes. They adhere to the platelet membrane blocking its function and inhibiting the release of the necessary thrombocytic components for the second phase of the aggregation. This platelet alteration is not usually manifested clinically; for this reason no relationship was found between this platelet defect and the presence of hemorrhagic symptoms in our patients. The condition is reversible and may disappear after therapy with steroids and/or immunosuppresive agents.

[Hormonal multiplicity of an apudoma of the lung and pancreas. Characterization of the different peptides in the tumoral extracts (author's transl)]. / Multiplicidad hormonal en apudoma de pulmón y páncreas. Caracterización de los diferentes péptidos en los extractos tumorales.

The capacity which the cells of some tumors have of synthesizing, storing, and releasing hormonal polypetides constitutes the basic characteristic of the neoplasms of the APUD system. On many occasions these polypeptides are released as hormonal precursors of high molecular weight, with a minimal biological action in comparison with the real hormone (big ACTH, big gastrin, etc.), and they have no clinical expressivity. On other occasions they reproduce, however, the clinical syndrome of the hormone released in excess. The production of multiple hormones by a single tumor is not a common event. Here we present the case of a patient with an oat-cell carcinoma of the lung and a carcinoma of the pancreas, both histopathologically primitive. In this patient a syndrome of inadequate secretion of antidiuretic hormone was detected. By means of radioimmunoassay techniques, the existence of antidiuretic hormone, ACTH with a predominance of the components of high molecular weight (big ACTH and beta-LPH) and MSH was demonstrated in the tumoral extracts from the lung, pancreas, and from a mediastinal metastatic lymph node. While the concentrations of ACTH were much greater in the lung than in the pancreas, the opposite occurred for the antidiuretic hormone. The synthesis of MSH by the hypophyseal gland or by tumors is not at present recognized, but rather is considered as a degradation product during the process of extraction. The APUD system makes up the morphologic substrate of the syndromes of familiar multiple endocrine adenomatosis. The present case could represent a variant of sporadic multiple endocrine neoplasms which would have the same anatomical basis.

[Panarteritis nodosa with positive Australia antigen (author's transl)]. / Panarteritis nodosa con antígeno Australia positivo.

A case of panarteritis nodosa with positive Australia antigen is presented. Panarteritis appeared following serum hepatitis and caused arthromyalgia, abdominal pain, prolonged fever of unknown origin, peripheral polyneuropathy, blood hypertension, and renal insufficiency. A muscular biopsy showed atrophy due to denervation and necrotizing arteritis in various stages causing serious damage to the arteries. Abdominal arteriography clearly demonstrated the existence of aneurismal dilations in the liver, pancreas, and kidneys. The angiographic findings in panarteritis nodose are discussed with special reference to the aneurysms localized in several organs. Their situation is described in detail; it is usually abdominal and more specifically intrarenal. The fact that they occur in a high percentage of cases is helpful when establishing the diagnosis. Lastly, the role of Australia antigen in the development of panarteritis nodose is discussed. It stimulates an immune response and the production of circulating immunocomplexes which are depostied on the vascular walls with complement fixation and damage to the blood vessels. The possibility that other viral agents may be present in the various types of necrotizing vasculitis in humans is commented on.

[Self-limited idiopathic fever. A study of twenty cases (author's transl)]. / Fiebre idiopática autolimitada. Estudio de 20 casos.

Out of 23 cases with a final diagnosis of idiopathic fever, 20 had self-limited fever with complete resolution. Comparing the cases of self-limited fever with other groups of patients with fever of unknown origin, the following differences were apparent: compared with tumoral and collagen diseases, self-limited fever occurred more frequently below age 40, the difference being significant (p less than 0.01). Chills occurred more frequently in self-limited fever than in tumoral and collagen diseases, while the incidence was similar in infectious diseases. Infectious, tumoral and collagen diseases presented with significantly greater weight loss (p less than 0.01) than self-limited fever. A greater incidence of hepatosplenomegaly was noted in self-limited fever than in infectious diseases. Hemoglobin and erythrocyte sedimentation rate (ESR) were significantly higher in self-limited fever than in the other illnesses. The NBT test was positive, with a reduction superior to 30% in the six cases in whom it was performed. In nine cases various invasive procedures were utilized: radiology, biopsy, laparoscopy (two cases), and laparotomy (one case). The data on the present series of self-limited idiopathic fever support an infectious origin of the disease because of the following: absence of an age difference with the group with a demonstrated infectious cause; fever of less than two months duration in most cases; presence of chills and less incidence of weight loss, anemia, and elevated ESR in relation to the other groups of fever of unknown origin; a positive NBT test; and spontaneous evolution to complete resolution of the disease.

[Fever of unknown origin with a prolonged course (author's transl)]. / Fiebre de origen desconocido de larga evolución.

Out of 110 cases of fever of unknown origin (FUO) that met Petersdorf and Beeson's criteria 15 patients were selected because of prolonged FUO with more than six months elapsed between admission and the final diagnosis. In this group of chronic FUO an etiological diagnosis was reached in 11 cases, distributed as follows: four cases with infections (two with toxoplasmosis, one with brucellosis, and another with a brain abscess); one with colon carcinoma; two with collagen-vascular diseases (systemic lupus erythematosus, temporal arteritis); and four with different diseases (two with familial mediterranean fever, one with idiopathic granulomatous disease, and another with factitious fever). In four cases no cause for the FUO could be determined. The procedures used to obtain the diagnosis were non-invasive in five cases (clinical course and serological tests), and invasive in another five (angiography, biopsies, and exploratory laparotomy). In one case the ethology could only be ascertained at autopsy. In the FUO with a prolonged course the peculiar etiological spectrum, the lesser yield of invasive procedures, and a mortality inferior to that of FUO in general all deserve special emphasis.

[Classical panarteritis nodosa: a clearly defined entity. Analysis of 20 cases (author's transl)]. / La panarteritis nodosa clásica: una entidad claramente definida. Análisis de 20 casos.

The clinical, biological, and immunological alterations of 20 patients with histologically confirmed classical panarteritis nodosa have been studied. Characteristic angiographic changes were present in 14 cases. There were 14 males and six females, with a mean age of 50 years. The main clinical manifestations were: fever (90%), peripheral nervous system involvement (80%), renal involvement (65%), arterial hypertension (60%), arthropathy (80%), and cutaneous lesions (45%). In most cases there was elevated VSG and alpha 2-globulin, anemia and leukocytosis. HBsAg positivity was found in five patients. The immunological study revealed a polyclonal immunoglobulin increase, changes in the complement components, and a quantitative and qualitative decrease of T lymphocytes. Steroids and immunosuppressive treatment were given to eight patients, and steroids along to 11 patients. The clinical evolution of 17 patients was followed; four patients died, all of them belonging to the group treated with steroid alone.

[The spectrum of lupus nephropathy]. / El espectro de la nefropatía lúpica.

Clinical manifestations and immunological characteristics in a series of 15 patients with systemic lupus erythematosus and renal involvement are presented. These findings have been correlated to different pathologic lesions and compared to another series of patients without renal involvement. The overall rate of renal involvement was 25 percent, with ages ranging from 14 to 47 years. A female predominance was noticed. Histopathologic findings were as follows: focal glomerulonephritis (five cases), and minimal changes (one case). Under a histological glomerulonephritis (two cases); membranous glomerulonephritis (one case), and minimal change (one case). Under a histological standpoint the earliest lesions had the worse prognosis. Patients with diffuse glomerulonephritis showed a high degree of renal function impairment. Urinary infection was present in half of the cases. A significant hyperlipidemia was found in patients with nephrosis. Proteinuria and abnormal urinary sediment were common findings in all histologic types. Antinuclear antibodies, were positive in 14 cases, with statistical significant high titres in diffuse glomerulonephritis. Serum immunoglobulins IgG and IgA were elevated. Decrease of serum complement levels (C3, C4, C3PA and C5) were found in patients with renal involvement.

[Coeliac disease in the adult]. / Enfermedad celiaca del adulto.

Coeliac disease can by defined as a chronic disease characterized by a typical mucosal lesion of the small intestine and an impaired nutrient absorption which improves on withdrawal of gluten from the diet. The prevalence rate has increased over the last decades and just 1/3 of cases are diagnosed in childhood. There is a striking association with class II histocompatibility antigens, HLA-DR3 and HLA-DQ2. Cellular immune response mediated by intraepithelial and lamina propria lymphocytes is the primary event in the small intestine damage. Up to 50% of adult coeliac patients don't present intestinal symptoms being more frequent subclinic forms. The immunological markers of coeliac disease are antigliadin, antireticulin and antiendomysial antibodies, being the last one the most specific. Mortality of coeliac patient is increased mainly for malignancies, being the most frequent the intestinal T lymphoma.

[Prions: definition and diseases]. / Priones: concepto y enfermedades.

In this article we review the concept and terminology of prions, their replication and some current hypothesis on the nature of these infectious agents causing neurodegenerative diseases. This revision also summarizes the etiopathogenic, epidemiological, clinical and neuropathological features of the prion diseases or human transmissible spongiform encephalopathies, and some methods for their early diagnosis. Finally, we discuss the possible link between the bovine spongiform encephalopathy and the new cases of Creutzfeldt-Jakob disease identified in the United Kingdom.

[Capillaroscopy in vasculitis]. / Capilaroscopia en las vasculitis.

A prospective study of the capillaroscopy changes in 15 patients afflicted with vasculitis is presented. 2 of them had classic polyarteritis nodos (PAN), 3 had Churg-Strauss allergic angiitis and granulomatosis, 2 had hypersensitivity vasculitis (HV), 6 had giant-cell arteritis (GCA) and 2 had polyangiitis overlap syndrome (POS). Periungual capillaroscopy (PC) showed isolated changes in 11 patients (73%). We observed more changes in those cases with active disease (83% vs. 67%); they were mainly microhemorrhage (without any statistical significance). There were no more findings in patients with a more generalised affliction (nervous system, kidneys and/or skin) than in the others. In conclusion, the capillaroscopy findings were few and non-specific. PC is a diagnostic method of negligible value in this type of disease.

[The polyangiitis overlap-Schönlein-Henoch purpura-PAN syndrome: a case of more than a rare association]. / Síndrome poliangeítico de solapamiento púrpura de Schönlein Henoch-PAN: un caso más de una rara asociación.

A fifty-four-years old male with palpable purpura, polyarthritis and nephritic syndrome is presented. The renal biopsy disclosed mesangial proliferation with IgA deposits. During hospitalization abdominal pain and upper digestive bleeding also presented. Digital angiography showed splenic artery microaneurysms. Then it's a new case of polyangiitis overlap with mixed features of Schönlein-Henoch purpura and polyarteritis nodosa. Differential diagnosis between several vasculitic associations in a patient is discussed.

[Fabry's disease associated with rheumatoid arthritis. Multisystemic crossroads]. / Enfermedad de Fabry asociada a artritis reumatoide. Una encrucijada multisistémica.

Fabry's disease is a rare congenic disorder of glycosphingolipid catabolism resulting from deficient activity of the alpha galactosidasa. Is an X-linked disorder and in hemizygous males the activity of this enzyme is very low, resulting in severe manifestations. Fabry disease is confirmed by the lack alfa-galactosidase in serum. In the literature have been reported a few cases of coexistent Fabry's disease and connective disorders, but there is not cases of rheumatoid arthritis coexistent. This report describes a case of a female with Fabry's disease who vas subsequently diagnosed with rheumatoid arthritis. The suspect diagnosis was very important because the two disorders are multisystem and new symptoms could be attributed to Fabry's disease. The accumulation of lipids may results in numerous pathogenic autoantibodies, which could make immunocomplex. This is the potential pathogenic mechanisms explaining the association between Fabry's disease and autoimmune diseases.

[Homocysteine. The cardiovascular risk factor of the next millennium?]. / La homocisteína. El factor de riesgo cardiovascular del próximo milenio?

Several epidemiologic studies have demonstrated that hyperhomocysteinemia is a risk factor for arteriosclerosis in coronary, cerebral, peripheral and aortic arteries. This risk is independent of other cardiovascular risk factors, and it is dose related. However, prospective studies show contradictory findings. Hyperhomocysteinemia is also associated with a higher risk of venous thrombosis to which other coagulation disorders, such as factor V Leiden, could contribute. Hyperhomocysteinemia can be due to genetic defects in the enzymes that control homocysteine metabolism, and also to other factors, mainly nutritional (deficiencies in vitamin B6, vitamin B12, or folic acid). Dietary supplements of these vitamins reduce plasma homocysteine levels. Randomized clinical trials are still needed to demonstrate that reducing plasma homocysteine levels will reduce the risk for cardiovascular disease.

[Adult celiac disease presenting as tetany]. / Tetania como forma de presentación de la enfermedad celíaca del adulto.

Tetany is a rare form of presentation of adult celiac disease. We present three patients with spontaneous episodes of tetania who were finally diagnosed of celiac disease. All were women. In two of them an unexplained chronic anemia was previously detected. The origin of tetania was severe hypocalcemia and hypomagnesemia. After intravenous restoration of calcium and posterior free gluten diet with supplements, clinical and biological remission was achieved. In the presence of isolated tetania or unexplained anemia resistant to treatment an adult celiac disease must be disclosed.

[Pathology related to infection with human immunodeficiency virus]. / Patología relacionada con la infección por el virus de la inmunodeficiencia humana.

HIV not only helps in producing secondary infections by altering the immunology system, as we showed, it is directly responsible for several diseases, mainly in CNS. As further experience is gained, the magnitude of the disease will become more evident, along with just how few therapeutic advances have been made.