Splenomegaly,Macrothrombocytopenia and Stomatocytosis in Healthy Mediterranean Subjects (Splenomegaly in Mediterranean Macrothrombocytopenia)

Spleen size, stomatocytosis, macrothrombocytopenia, haemoglobin level, white cell count, and abdominal pain episodes were assessed in a coded study of healthy Mediterranean immigrants to Australia. Spleen size was estimated from a length measurement, L, on a standardized plain abdominal radiograph and expressed both as spleen weight and as a spleen length index, L/l/BSA; the platelet count and size parameters were determined electronically and the presence of stomatocytes was evaluated in stained blood films. In relation to 16 Northern European control women 12 of 25 Mediterranean women had radiographic splenomegaly, 10 had macrothrombocytopenia, 9 had stomatocytosis, but none had episodes of abdominal pain. The median spleen weights of the two groups were estimated as 157 and 247 g with ranges from percentile 2.3 to 97.7 of 75 to 328 and 112 to 669 g. Within the Mediterranean group splenomegaly correlated with macrothrombocytopenia (P < 0.001) but not with stomatocytosis, haemoglobin values or white cell counts. Thus, mild splenomegaly may be expected in Mediterranean macrothrombocytopenia, Mediterranean stomatocytosis appears unrelated, and all of these apparently benign anomalies may be incidental findings in patients from the Italian and Balkan peninsulas.     

Hyper-reactive Malarial Splenomegaly (HMS) in malaria endemic area in Eastern Sudan

Hyper-reactive Malarial Splenomegaly (HMS) is massive enlargement of the spleen resulting from abnormal immune response to repeated attacks of malaria. The present study was carried out in Kassala city, Eastern Sudan where HMS is considered as highly prevalent. The objectives of this study were to determine the incidence of HMS in Eastern Sudan, and to identify basic laboratory and clinical characteristics of this condition in Sudanese patients. In the period between January and March 2004, a cross-sectional study was carried out in four health centers in Kassala city. In the current study 114 out 1010 (11%) medical cases examined were found to have enlarged spleens, 87 (9%) of them were diagnosed as HMS. Sixty-three percent of HMS cases were males and the rest were females. The mean age of HMS patients was 28 years. Clinical investigations showed that all cases suffered from abdominal pain in the upper left quadrant and all had a palpable firm spleen (10-26cm) below the costal margin. Laboratory examinations showed that 74% of the cases were anaemic and the mean white blood count for all cases was 4237cell/mL(3). Serum concentration of IgM in all subjects was above the threshold of the mean value plus 2 S.D. for 35 asymptomatic controls. In more than 70% of the HMS patients (53 individuals) the spleens were impalpable after the third month of the treatment. Our data indicate that HMS is one of the major causes of tropical splenomegaly in Eastern Sudan.     

Splenectomy in patients with malignant lymphoma presenting with massive splenomegaly

6 patients with massive splenomegaly but no peripheral adenopathy were diagnosed by splenectomy as having lymphoma; and were found to have widespread disease. Despite the seriousness of their illness at presentation, all have survived for a median time of 101.5 months and reached complete remission.     

Megaloblastic Anemia Presenting with Massive Reversible Splenomegaly

Megaloblastic anemia (MA) is a common disorder with varied manifestations. It generally results in mild to moderate splenomegaly which is due to sequestration of macrocytic erythrocytes in spleen. Massive splenomegaly is generally seen in infections, myeloproliferative diseases, neoplasms, storage disorders or hematological conditions; but is not heard of and has rarely been reported in MA. We discuss a case of massive splenomegaly who presented with symptomatic anemia and was found to have MA. He was extensive evaluated for all other causes of massive splenomegaly which was normal. Further, after a therapeutic trial of MA he showed a regression in spleen size confirming that the massive splenomegaly was attributable to MA.     

Progressive Massive Splenomegaly in an Adult Patient with Kabuki Syndrome Complicated with Immune Thrombocytopenic Purpura

Kabuki syndrome is characterized by multiple systemic anomalies and intellectual disability. It is complicated with immunodeficiencies and autoimmune disorders. The syndrome is caused by a mutation in the KMT2D gene. We herein report a case of a Kabuki syndrome with developing immune thrombocytopenic purpura (ITP) and progressive splenomegaly. Laparoscopic splenectomy was performed and the patients'' symptoms quickly disappeared with platelet recovery. After this operation, the patient had no severe complications. A sequence analysis of the KMT2D gene identified a pathogenic mutation frequently associated with ITP. Laparoscopic splenectomy is therefore considered to be a good therapeutic option for recurrent ITP and symptomatic splenomegaly with Kabuki syndrome.     

Helicobacter pylori infection is probably the cause of chronic idiopathic neutropenia (CIN)-associated splenomegaly

Splenic volume and Helicobacter pylori (H. pylori) infection were evaluated in 67 patients with chronic idiopathic neutropenia (CIN) and 39 healthy individuals. Using ultrasound, splenomegaly was found in 61.7% of H. pylori-infected subjects compared to only 8.7% noted in the group of H. pylori-non-infected individuals (P < 0.0001). Splenomegaly was also found in 47.8% of CIN patients compared to 12.8% in the group of non-CIN subjects (P = 0.0003). However, applying the two-way ANOVA test, a statistically significant effect on splenic volume was documented for "factor H. pylori " (F1(102) = 16.800, P < 0.0001) but not for "factor CIN" (F1(102) = 3.213, P = 0.0760), suggesting that CIN-associated splenomegaly is probably due to H. pylori infection.     

Chronic Idiopathic Hyponatremia in Older People Due to Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) Possibly Related to Aging

OBJECTIVE: To determine the prevalence of syndrome of inappropriate antidiuretic hormone secretion (SIADH) among older hyponatremic patients in a subacute geriatric facility, to identify patients with no apparent cause for the SIADH (idiopathic SIADH), and to determine their clinical characteristics. DESIGN: Prospective analysis of a cohort of older patients over a period of 3 months. SETTING: Two wards in a geriatric rehabilitation hospital. PARTICIPANTS: Patients aged 65 and older. MEASUREMENTS: All patients with hyponatremia (serum sodium <135 mmols/l) were clinically examined and relevant investigations were performed to determine the etiology of hyponatremia. Patients were observed for symptoms of hyponatremia. Hyponatremia was classified into possible SIADH and non-SIADH types. Patients with SIADH type hyponatremia were screened for possible causes. Past medical histories were obtained from the general practitioners. RESULTS: Of the 172 patients studied, 43 (25%) had hyponatremia. It was symptomatic in only four patients. Twenty-two (51%) had SIADH etiology. In nine (mean age 84 +/- 4), no cause for the SIADH was evident (presumed idiopathic SIADH) and in seven, hyponatremia (128-135 mmols/l) was chronic (12 to 72 months). Further reduction in serum sodium, which was symptomatic, was noted in two of these patients with the onset of pneumonia. CONCLUSION: Most older hyponatremic patients in a rehabilitation setting seem to have SIADH etiology. This study confirms the presence of a group of older individuals with chronic idiopathic hyponatremia in whom the underlying mechanism may be SIADH related to aging. Hyponatremia is modest in these patients and has little clinical significance. However, they may be at increased risk of developing symptomatic hyponatremia with intercurrent illnesses.     

Splenomegaly, hypersplenism and coagulation abnormalities in liver disease

Splenomegaly is a frequent finding in patients with liver disease. It is usually asymptomatic but may cause hypersplenism. Thrombocytopenia is the most frequent manifestation of hypersplenism and may contribute to portal hypertension related bleeding. A number of therapies are available for treating thrombocytopenia due to hypersplenism including splenectomy, partial splenectomy, partial splenic embolization, TIPS etc. None is entirely satisfactory. Hypersplenism usually improves following liver transplantation. Therapy with cytokines such as thrombopoietin may offer hope for the future. Patients with liver disease also have abnormalities in coagulation. This is not surprising as all coagulation proteins (except for von willebrand factor vWF) and most inhibitors of coagulation are synthesized in the liver. Genetic or acquired abnormalities of coagulation may predispose to thrombosis of the hepatic or portal veins with significant clinical sequelae. An understanding of the mechanisms involved in coagulation and thrombosis is valuable in choosing from the increasing treatment options available. These include clotting factors, haemeostatic drugs and newer therapies such as recombinant factor VIIa. Splenic artery aneurysms are the most common visceral artery aneurysms in man. Rupture is frequently catastrophic. These aneurysms are being increasingly recognized in liver transplant patients and require treatment before or during transplant surgery.     

Thalidomide for the treatment of idiopathic myelofibrosis

Except rare instances of allogeneic stem cell transplantation, treatment of idiopathic myelofibrosis (IMF) is only palliative and based on cytostatic treatment (hydroxyurea and anagrelide), androgen therapy, steroids and splenectomy. Thalidomide is an anti-angiogenic and immunomodulatory drug with a wide spectrum of activities, which are not clearly understood. Current data suggest that the action of thalidomide is related to several different mechanisms, including suppression of tumor necrosis factor, effects on basic fibroblast growth factor, vascular endothelial growth factor, interleukins and interferons, downregulation of selected cell surface adhesion molecules, and changes in the lymphocyte subsets. We administered thalidomide to 16 patients with IMF (15 men, one women) who had transfusion-dependent anemia, thrombocytopenia or symptomatic splenomegaly. Median age was 59 yr (range: 52-78). Patients received thalidomide at an escalating dose from 100 to 400 mg/d (median 300 mg). The drug was discontinued in four patients because of progressive disease (two) or polyneuropathy (two). Other adverse effects were obstipation (10), fatigue (eight) and edema (two). Clinical response has now been observed for a median duration of 9 months (range: 3-20). Fifteen patients are evaluable. Anemia improved in six of 10 patients who were anemic. Platelet counts improved in five of seven patients with thrombocytopenia. Splenomegaly regressed in three of 13 patients. Lactate dehydrogenase (LDH) decreased in seven of 12 patients, but increased in four patients. LDH levels were not correlated with clinical response. In summary, thalidomide appears useful in the treatment of IMF.     

True idiopathic splenomegaly - a distinct clinical entity

10 asymptomatic young male patients with moderate splenomegaly detected at a routine examination are presented. The history and clinical examination failed to reveal the aetiology of the splenomegaly. Further investigations, including screening for blood dyscrasias, clotting abnormalities and reticuloendothelial abnormalities were likewise unrevealing. Liver biopsies, rectal biopsies for bilharzia and bone marrow aspirates for Gaucher's Disease were found to be normal. Serology for malaria and Ebstein Barr Virus infection was also negative. Positive immunofluorescent tests for IgG antibodies specific for cytomegalovirus were found in 5 patients. We consider that these patients have splenomegaly which is not of a specific nature, but may be associated with a severe antigeneic response to the previous cytomegalovirus infection. In view of the otherwise negative findings these patients should be considered to have ‘True Idiopathic Splenomegaly’, a term which would indicate the benign nature of the splenic enlargement. This diagnosis should be considered in the differential diagnosis of asymptomatic patients who have splenomegaly of undetermined origin.     

Inverse Relationship between Splenomegaly and Stem Cell Compartment Size in Mice Treated with Nitrogen Mustard

Following the administration of similar doses of nitrogen mustard (4 mg/kg) to different strains of mice, wide variations in the subsequent degree of splenomegaly were observed, implying strain differences in the role of the spleen in the compensatory erythropoietic response to haematopoietic stress. This investigation was undertaken to determine whether or not these differences were related to the size of the haematopoietic stem cell compartment size in the various strains of mice. Groups of 4 different strains of mice (Swiss Webster, A/J, C57BL/6J and CS1/ASH) were injected i.v. with nitrogen mustard (4 mg/kg body weight) and autopsied at regular intervals up to 20 d post-injection. At autopsy, the wet weight of the spleen was determined. Subsequently, groups of the same 4 strains of mice were exposed to single doses of wholebody γ-irradiation in the range of 500–900 rads. 9 d after γ-irradiation the mice were autopsied, their spleens removed, and the number of endogenous spleen colonies determined. The greatest degree of splenomegaly was observed in the C57bl/6J mice. The Swiss Webster mice showed no splenomegaly during the time period studied. There existed a linear inverse relationship between the maximum degree of splenomegaly observed and the dose of wholebody γ-irradiation required to completely eliminate endogenous spleen colonies. This data is in accord with the hypothesis that there exists an inverse relationship between the extent of splenomegaly observed following haematopoietic stress and the haematopoietic stem cell compartment size.     

Enhanced expression of poly(ADP-ribose) synthetase gene in malignant lymphoma

Over-expression of cellular protooncogenes has been proposed to function in the initiation and maintenance of malignancies. In order to distinguish malignant lymphoma from reactive proliferative diseases, we surveyed the expression levels of three protooncogenes(c-myc, c-fos and c-myb) in malignant lymphoma and reactive proliferative diseases. An increased level of c-myc or c-fos mRNA was observed in one case, respectively, out of three malignant lymphomata. The other cases exhibited no enhancement in protooncogenes. These oncogenes are critically regulated during differentiation, but the half-life of c-myc mRNA was very short, and the level of the mRNA decreased to the initial level very quickly. Thus, the high level of the expression of these oncogenes may not always be maintained in all malignant cells. We then examined the level of mRNA for poly(ADP-ribose) synthetase in those cases. An enhanced expression for the synthetase gene was observed in all five malignant lymphomata tested, but no increase in the level of the mRNA was observed in any reactive proliferative cases or normal lymph nodes. These results suggest that enhanced expression of poly(ADP-ribose) synthetase gene seems to be a common characteristic of protopathic malignant lymphoma. By using the characteristics of malignant lymphoma, the level of mRNA for the synthetase may be applicable for differential diagnosis of malignant lymphoma from several pathologically indistinguishable diseases.     

Idiopathic environmental intolerances (formerly multiple chemical sensitivity) psychiatric perspectives

Idiopathic environmental intolerances (IEI)/multiple chemical sensitivity (MCS) is characterized by various somatic symptoms which cannot be explained organically, but are attributed to the influences of toxic environmental chemicals in low, usually harmless doses. In the absence of a widely accepted definition of IEI, contradictory aetiological hypotheses and therapeutic suggestions are discussed. Some authors doubt the existence of IEI/MCS as a disease entity of its own. The label IEI does not implicate neither a diagnosis of somatic disease nor that it is caused by an avoidable exposure. Many IEI patients suffer from psychiatric diseases. A majority of them can be diagnosed as somatoform disorders. Consequently, psychiatric therapies could be effective. This review describes the current knowledge about IEI/MCS, outlines a diagnostic algorithm and a psychotherapeutic concept for variants of IEI understood as a somatoform disorder.     

Idiopathic ulcer of the small bowel containing numerous plasma cells: case resembling mucosa-associated lymphoid tissue lymphoma

Idiopathic ulcer of the small bowel is a poorly recognized entity. Herein is reported a case of idiopathic ulcer of the jejunum containing numerous lymphoplasmacytoid infiltrates and mimicking mucosa-associated lymphoid tissue (MALT) lymphoma. An 82-year-old Japanese woman presented with nausea and vomiting. Following diagnosis of submucosal tumor, partial jejunal resection was performed. Macroscopically the resected specimen contained multiple small shallow ulcers. Histologically the lesion was composed of numerous plasma cells mixed with lymphocytes and histiocytes. Immunohistological study revealed that the plasma cells contained polytypic intracytoplasmic immunoglobulins. The patient remained free of disease after 36 months. Marginal zone B-cell lymphoma of MALT-type arising from small intestine occasionally shows prominent plasma cell differentiation. The present case demonstrates that idiopathic ulcer of the small bowel should be added to the differential diagnosis of MALT-type lymphoma of the small bowel.     

Idiopathic recurrent pancreatitis

The cause of recurrent acute pancreatitis can be identified in the majority of patients. A small group of patients in whom an etiological association is not obvious is characterized as idiopathic recurrent pancreatitis (IRP). During the last seven years, we used endoscopic retrograde cholangiopancreatography (ERCP) and sphincter of Oddi (SO) manometric pressure studies to investigate 116 patients initially diagnosed as IRP. Forty-four of the 116 patients were found to have a demonstrable cause of their pancreatitis. Appropriate therapeutic intervention was carried out in 43 of these patients with a favorable outcome in the majority of patients noted during long-term follow-up.     

Idiopathic Ventricular Fibrillation

Idiopathic Ventricular Fibrillation. Idiopathic ventricular fibrillation is defined as cardiac arrest in the absence of structural heart disease and other identifiable causes of ventricular fibrillation. It occurs in 1% to 9% of survivors of out-of-hospital cardiac arrest. The mean age of these patients is 35 to 40 years, and 70% to 75% are male. The pathogenesis is unknown; psychosocial factors may play a role. Baseline clinical characteristics have not been found to identify the 20% to 30% of patients who will have recurrent cardiac arrest. At present, implantation of an automatic defibrillator is the treatment of choice. Two registries have been established to enhance our knowledge of this unusual catastrophic entity.     

Quantitative Determination of Splenic Red Blood Cell Destruction in Patients with Splenomegaly

In order to evaluate a method permitting quantitation of splenic red blood cell destruction, a model of erythrocyte destruction in enlarged spleens was created: Erythrocytes are destroyed in the splenic erythrocyte pool at a constant rate, producing in labelling studies hyperhaemolysis due to random destruction. A mathematical analysis of the model shows that the splenic destruction rate can be calculated with great accuracy from quantitation of the initial excess radioactivity, measured over the spleen during the first days after infusion of ⁵¹Cr-labelled autologous erythrocytes. 18 patients with splenomegaly (479–4700 g) were investigated. The splenic erythrocyte destruction rate was estimated to be between 0.5–4.4% of the total erythrocyte mass per day, increasing significantly with increasing splenic weight. The results indicate that erythrocyte destruction takes place almost exclusively in the enlarged spleen in cases of predominant splenomegaly without complicating immunohaemolysis.     

Aseptic Meningitis-retention Syndrome Associated with Tocilizumab in a Patient with Idiopathic Multicentric Castleman Disease

This is the first report of tocilizumab-associated meningitis-retention syndrome in a patient with idiopathic multicentric Castleman disease. A 57-year-old man presented with headache, nuchal rigidity, impaired consciousness, pyramidal tract signs and urinary retention. A cerebrospinal fluid examination revealed increased cell counts and protein levels. These symptoms were improved by intravenous methylprednisolone. Tocilizumab-associated meningoencephalitis has been reported in patients with rheumatoid arthritis and juvenile idiopathic arthritis but not with multicentric Castleman disease. This case presents evidence of the increased probability of meningitis as a neurological complication of tocilizumab administration.