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Splenomegaly in sarcoidosis.

The clinical records of 32 patients with sarcoidosis associated with splenomegaly were reviewed. The results of this study disclosed that when compared with a matched control population without splenomegaly, patients with splenomegaly had evidence of more extensive extrathoracic sarcoidosis. In contrast, there was no difference in the degree of pulmonary involvement between patients with or without splenomegaly. Of the 32 patients with splenomegaly, seven (20%) had evidence of hypersplenism and five (16%) had abdominal symptoms. These abnormalities occurred only in patients with greatly enlarged spleens. Considering splenomegaly, we suggest that corticosteroids are indicated in the management of only large spleens and not of smaller spleens, unless there are other specific indications.

Adrenal Cortex Hormones↗

Splenomegaly in sarcoidosis: a report of 16 cases.

The reported frequency of splenomegaly in sarcoidosis has ranged from 1% to 40%. Splenomegaly has been associated with clinical evidence of more extensive extrathoracic sarcoidosis. In a previous study, we reported that splenomegaly was associated with a poor outcome of the disease. The aim of the present study was to describe the characteristics of the sarcoidosis patients with splenomegaly seen at our institution. Of 284 sarcoidosis patients, followed up at our hospital, 16 (5.6%) had splenomegaly on physical examination. These patients showed other extrathoracic manifestations as well, and all but two showed intrathoracic involvement. Eleven patients received corticosteroid therapy. Splenectomy was done in three patients, but the natural history of their sarcoidosis remained unaltered two years after diagnosis. The results of this study disclosed that patients with splenomegaly had evidence of extensive pulmonary and extrathoracic sarcoidosis with a poor prognosis in spite of steroid therapy.

Adolescent↗

Splenomegaly in 2,505 patients at a large university medical center from 1913 to 1995. 1963 to 1995: 449 patients.

Splenomegaly was studied retrospectively at the University of California, San Francisco (UCSF), School of Medicine in 301 patients from 1963 to 1995 and compared with the UCSF service of the San Francisco General Hospital Medical Center (SFGH) in 148 patients from 1979 to 1994. The combined 449 patients were classified into several diagnostic groups and were studied by means of several clinical and laboratory associations. Hepatic disease in the percentage of patients at UCSF (with those at SFGH given in parentheses) was associated with splenomegaly in 29% (41%), hematologic disease, 32% (16%); infectious diseases, 16% (36%); congestive or inflammatory disease, 10% (4%); primary splenic disease, 6% (1%); other, 5% (1%); and cause unknown, 2% (1%). Massive splenomegaly occurred in 27% of the patients of the combined series, particularly in patients with hematologic diseases. The acquired immunodeficiency syndrome (AIDS) occurred in more than half of the patients with infectious diseases at SFGH and was four times frequent than in the patients at UCSF. The commonest diseases associated with splenomegaly were hematologic (lymphoma), hepatic (chronic liver disease), infectious diseases (AIDS and endocarditis), congestive (congestive heart failure), primary splenic (splenic vein thrombosis), and other (malignancy not metastatic to the spleen). In 11 patients with AIDS and massive splenomegaly, Mycobacterium avium complex occurred in 8 (73%). Splenectomy was performed in 117 patients (26%), primarily for hematologic amelioration. I conclude that for splenomegaly of unknown origin, the invasive procedure of choice for patients with hematologic associations may be a bone marrow biopsy; for hepatic association, a liver biopsy; and for infectious disease associations, a lymph node biopsy, before any consideration of a diagnostic splenectomy.

Acquired Immunodeficiency Syndrome↗

Malignant histiocytosis with massive splenomegaly in asymptomatic patients. A possible chronic form of the disease.

Four patients with malignant histiocytosis (MH) are described whose initial manifestation of the disease was massive splenomegaly without associated systemic symptoms. The diagnosis of MH was made after histologic evaluation of splenectomy specimens. Splenomegaly in an otherwise asymptomatic patient is unusual for malignant histiocytosis, but when such a clinical picture is seen, it may be confused with other diseases that often present with massive splenomegaly and that have a similar diffuse infiltrative pattern in the spleen. Although three of these patients did eventually develop systemic symptoms characteristic of MH 3, 6, and 10 months after the detection of splenomegaly, the 15-month asymptomatic survival of one patient who received no chemotherapy suggests that MH presenting with massive splenomegaly, rather than with constitutional symptoms, may have a protracted course.

Abdomen↗

Fibrocongestive splenomegaly in sickle cell disease: a distinct clinicopathological entity in the Eastern province of Saudi Arabia.

Sickle cell disease displays a unique progression in the Eastern province of Saudi Arabia, where splenomegaly with hypersplenism is noted with high frequency in the adolescent and adult patients. The late persistence of splenomegaly although likely reflects the milder progression of sickle cell disease in this region; nevertheless, it predisposes the patients to increased morbidity. The present study documents the characteristic clinicopathological features of splenomegaly associated with sickle cell disease in the Al-Hassa region of Eastern province Saudi Arabia. Forty-four cases of sickle cell disease patients in whom splenectomy was performed during 1999-2003 were studied. The hemoglobinopathy profiles of the patients (age range 5-42 years) comprised sickle cell anemia (8 cases), sickle cell anemia with high fetal hemoglobin (23 cases), and sickle cell-beta degrees thalassemia (13 cases). All patients had manifestations of hypersplenism and 39 patients experienced episodes of minor-type sequestration crisis. Splenectomy was effective in ameliorating the hematological abnormalities in all cases, without any major complications in the follow-up period. The splenectomy specimens showed moderate-to-marked enlargement in most cases, with histological features of fibrocongestive splenomegaly and prominent Gandy-gamma body formations. Micro-infarcts in 27 cases and gross infarctions in 9 cases were evident. The relationship of persistent splenomegaly with higher fetal hemoglobin levels and splenic hypofunction is examined along with the significance of splenectomy in these cases.

Adolescent↗

Platelet transfusion therapy in acute leukemia: lack of effect of splenomegaly on transfusion requirements and risk of hemorrhage.

Platelet transfusions are an important supportive measure during treatment for acute nonlymphocytic leukemia (ANLL). The presence of splenomegaly may produce decreased posttransfusion platelet increments leading some to recommend an increased dose of platelets per transfusion in this situation. Forty-nine newly diagnosed patients with ANLL were evaluated during 1980 and 1981, and 24% had palpable splenomegaly. Although treated with usual doses of platelets per transfusion, there was no detectable statistical increase in transfusion requirement or incidence of hemorrhage in patients with splenomegaly. Experimental evidence indicates that the splenic platelet pool enlarges with splenomegaly, but the life span of circulating platelets is not significantly changed. Furthermore, the splenic platelet pool is in dynamic equilibrium with the circulating platelet pool thus allowing these platelets to participate in hemostasis. Although posttransfusion increment in platelet count may be less, it appears that platelet transfusion therapy need not be altered solely because of splenomegaly.

Acute Disease↗

Inhibition by streptovaricins of Rauscher leukemia virus splenomegaly.

Streptovaricins (Sv), ansa macrolide antibiotics, inhibited Rauscher leukemia virus (RLV) splenomegaly by 25-50%. All streptovaricins tested were effective when administered orally either by diet ad lib or by intubation from infection to time of killing. When delivered by intubation, Sv was measurable in plasma for up to 6 h. SvC, at 300 mg/kg/day, reduced mean spleen weight of infected mice from 478 plus or minus 51 (SE) mg to 300 plus or minus 55 (SE) mg. Rifampicin, at 250 mg/kg/day, had no similar activity. Decrease in caloric intake and in body-weight gain also resulted in an inhibition of RLV splenomegaly; although Sv-treated mice gained weight, the increase was usually slightly less than controls. However, mice treated with a Sv diet for a week prior to infection, after an initial period of weight loss, gained at a rate equivalent to control group, and when killed had a marked reduction in splenomegaly. The selectivity of streptovaricins and specificity for viral events was suggested by several observations: (1) Splenomegaly and mortality, induced by L1210 or a non-infective transplantable tumor of RLV origin, was not inhibited. (2) No inhibition of normal hematopoietic spleen colonies was observed. (3) Host immune responses, including cellular and humoral immunity and interferon production and action, were not inhibited. Thus, although the effect of slightly decreased weight and intake could not be unequivocally established, the findings were most compatible with a selective inhibition of RLV splenomegaly by Sv.

Animals↗

In vitro labeling and tissue autoradiography of splenomegaly associated with portal hypertension.

Sinus hyperplasia occurring in the congestive splenomegaly associated with portal hypertension is a interesting model of steady-state hyperplasia in an adult tissue. In vitro labeling of human splenic tissue with 3H-thymidine and the demonstration of S-phase cells by autoradiography was performed to investigate the proliferative activity of sinus-lining and cordal reticular cells in congestive splenomegaly compared with that in the normal spleen. The labeling index (%) of sinus-lining cells after 2 h incubation was 0.07 +/- 0.02 in the normal spleen and 0.26 +/- 0.03 in congestive splenomegaly (t = 4.553, P less than 0.005, n = 11). This result indicated that sinus-lining cells have a long life span and that their proliferative activity is increased in congestive splenomegaly. On the other hand, the labeling of cordal reticular cells and arterial and venous endothelial cells was sparse or absent in both congestive splenomegaly controls, and these cells do not appear to be involved in sinus hyperplasia.

Arteries↗

Diethylcarbamazine in the control of splenomegaly associated with Bancroftian filariasis in the Ok Tedi area of Papua New Guinea.

Bancroftian filariasis is highly endemic in the Ok Tedi region of Papua New Guinea, with a reported mean rate of 39% before the implementation of a single-dose diethylcarbamazine (DEC) treatment programme in 1986. This was followed by a 72% decline in the rate of detectable microfilaraemia and a 40% reduction in pre- and post-treatment splenomegaly. No significant difference was observed when spleen enlargement was compared to the presence of patent malaria. A significant difference in splenomegaly was observed between DEC-treated villagers and their untreated counterparts. Significant differences were reported in the rate of detectable microfilariae of Wuchereria bancrofti, but not of malaria, between the two groups. The number of DEC administrations and the period of time since the first treatment played a significant role immunologically. Significant differences were observed in immunoglobulin (Ig) M and IgG levels and in the extent of splenomegaly between DEC-treated and untreated areas. Filarial infection associated with malaria resulted in higher spleen rates and size. W. bancrofti is a major contributor to splenomegaly in the Ok Tedi region, and splenomegaly associated with bancroftian filariasis can be reduced or controlled by low, well-spaced doses of DEC.

Animals↗

Laparoscopic splenectomy for treatment of splenomegaly.

BACKGROUND: Laparoscopic splenectomy presents an advantage over open splenectomy, resulting in shorter hospital stay, decreased blood loss, and fewer operative and postoperative complications. Splenomegaly has long been considered a contraindication for laparoscopic splenectomy; however, in the hands of an experienced surgeon, this technique can be effectively applied to the treatment of splenomegaly. METHODS: Records for patients undergoing laparoscopic splenectomy for splenomegaly between 2000 and 2003, performed by a single surgeon in three community-based hospitals, were reviewed and demographic, operative, and postoperative data compiled. Preoperative diagnoses included B cell lymphoma, hemolytic anemia, and chronic lymphocytic leukemia. RESULTS: Seven patients underwent laparoscopic and hand-assisted laparoscopic splenectomy for splenomegaly during this time period. Splenic weights ranged from 410 to 3,100 g, and average operative time was 86.6 minutes. Estimated blood loss ranged from 50 to 350 ml; average hospital stay was 4.4 days. Two postoperative complications, ie, postoperative bleeding and superficial wound breakdown, were noted. CONCLUSIONS: Laparoscopic and hand-assisted laparoscopic splenectomy are effective methods for treatment of splenomegaly.

Aged↗

Ethnic differences in the prevalence of splenomegaly and malaria in The Gambia.

Significant variations in the prevalence of splenomegaly were found among members of the three main ethnic groups resident in North Bank Division, The Gambia. Among young children splenomegaly and malaria were less prevalent in Mandinkas than in Wollofs or Fulas, suggesting that some genetic or environmental factors protect Mandinka children from this infection. Among older children and adults splenomegaly was found most frequently in Fulas. Six of 22 adults with very large spleens had a high serum IgM level and probably had the hyperreactive malarial splenomegaly (tropical splenomegaly) syndrome. Four of these six subjects were Fulas. This finding, together with the results of a previous study in Nigeria, suggest that Fulas have a predisposition to this condition.

Adolescent↗

Persistent gross splenomegaly in Nigerian patients with sickle cell anaemia: relationship to malaria.

Serum IgM levels, hepatic histopathology, and response to prolonged proguanil treatment were investigated in 15 patients with sickle cell anaemia (SS), aged 8-15 years, with persistent gross splenomegaly (PGS). They were compared with age- and sex-matched SS patients without splenomegaly and with AA controls. The mean +/- SD serum IgM levels were 249.7 (75) mg/100 ml in the SS patients with PGS, 157.6(57.3) mg/100 ml in the SS patients without splenomegaly, and 146.2(48.9) mg/100 ml in the AA controls. The differences between these mean values were statistically significant (P less than 0.05). Hepatic histopathology in 11 of these patients showed moderate to severe sinusoidal dilatation and portal lymphocytic infiltration. Of the 13 patients that were followed on daily proguanil therapy, 10 showed remarkable reduction in splenic size within 6 months. The mean splenic size diminished by 13.8(3.2) cm to 5.6(5.3) cm over the period. The difference was statistically significant (P less than 0.01). This study has confirmed the previous belief that malaria plays a role in the aetiopathogenesis of persistent splenomegaly in sickle cell patients in a fashion similar to, but not quite the same as in, tropical splenomegaly syndrome (TSS). It also underscores the need for malaria chemoprophylaxis in these patients.

Adolescent↗

Massive splenomegaly in sarcoidosis.

We have presented a case of massive splenomegaly. Our patient was initially thought to have lymphoma, but at operation she was found to have sarcoidosis with splenic involvement. At 2250 g, the spleen was one of the largest recorded in the literature on sarcoidosis. Although the spleen is frequently involved in sarcoidosis, a review of 6074 cases showed that the incidence of actual splenomegaly is only 10%. In 628 of these cases the authors described various degrees of splenomegaly, but the incidence of massive splenomegaly was only 3%. We conclude that sarcoidosis must be considered in the differential diagnosis of splenomegaly.

Adult↗

Experimental models for prevention of graft-versus-host reaction in bone marrow transfusion. I. Selective suppression and augmentation of splenomegaly and cytotoxicity.

Induction and suppression of splenomegaly and cytotoxicity against C57BL/L cells were studied in (AKR X C57BL/6) F1 hybrid adult mice after the transfer of AKR lymphoid and bone marrow cells. 1) Splenomegaly and cytotoxicity were dissociated in the developmental stages of the graft-versus-host reaction. When lymphoid and bone marrow cells of normal AKR mice were injected into F1 recipients, splenomegaly was prominent on days 5 and 7, but cytotoxicity of spleen cells was not detected. Splenomegaly became less prominent but the cytotoxicity became detectable on day 14 after the injection. 2) Cytotoxic activity of spleen cells of F1 recipients was suppressed by the treatment of AKR donors with C57BL/6 lymphoid cells in Freund's complete adjuvant. Splenomegaly, however, was substantially enhanced by such a treatment of the donors. On the other hand, induction of the cytotoxic activity was facilitated by the treatment of donors with C57BL/6 skin grafts. 3) F1 hybrid mice could be protected from the graft-versus-host reaction by the injection of AKR anti-C57BL/6 serum or pretreatment of AKR donors with sonicated cellular antigens of C57BL/6.

Animals↗

Redefining the role of splenectomy in patients with idiopathic splenomegaly.

BACKGROUND: Despite extensive work-up to establish the cause of splenomegaly, splenectomy may be required for diagnosis in certain situations. The aim of this study was to find out the role of diagnostic splenectomy in the current era. METHODS: Between January 1989 and June 2004, 211 patients underwent splenectomy for indications other than trauma. In 41 (19%) patients, splenectomy was carried out for diagnostic purposes. Retrospective analysis of these patients was done for the purpose of the study. RESULTS: All patients who underwent diagnostic splenectomy had a complete haemogram, biochemical tests for liver and renal function, bone marrow biopsy and abdominal ultrasonography before splenectomy. There were 28 (68%) men and 13 (32%) women with median age of 37 years (range, 6-62 years). The median duration of symptoms was 12 months (range, 1-180 months). Common presentations were fever (n = 27; 66%), malaise (n = 26; 63%), pallor (n = 33; 80%) and gross splenomegaly (n = 27; 66%). Thirty-two (78%) patients had hypersplenism. Splenic lesions were shown in 14 (34%) patients on ultrasonogram and in 16 (39%) patients on contrast-enhanced computed tomography scan of the abdomen. Open splenectomy was carried out in all patients. Seventeen (41%) patients had postoperative complications. Among these, three (7%) patients had postoperative bleeding. One patient died because of acute respiratory distress syndrome. Final histopathology of the spleen showed lymphoma in 15 (37%), tuberculosis in five (12%) and other lesions in five (12%) patients. Sixteen (39%) patients had only congestive splenomegaly. CONCLUSION: A high proportion of patients presenting with idiopathic splenomegaly will have underlying haematological malignancies even in tropical countries. The clinical presentation, laboratory profile and imaging findings were not helpful in differentiating between patients with haematological malignancies and non-malignant conditions. Splenectomy still has an important role in establishing the pathology in patients presenting with idiopathic splenomegaly.

Adolescent↗

Splenomegaly--an insensitive sign of portal hypertension.

The prevalence of splenomegaly associated with portal hypertension was examined in a consecutive population of 111 patients who had portal hypertension diagnosed using specific endoscopic, sonographic, and Doppler signs. Splenic size was measured objectively via its cranio-caudal length on coronal section using ultrasound and by clinical examination. Sonographically, 52% of patients had a definitely large spleen and 35% a spleen less than one standard deviation from the normal mean, while a further 13% had equivocal splenomegaly. Only 52% of patients had splenomegaly on clinical assessment. Splenomegaly was less common in patients with alcoholic (41% definite, 15% equivocal) than in those with non-alcoholic liver disease (66% definite, 17% equivocal, p = 0.02) and splenic length was significantly smaller in alcoholic patients (12.7 +/- 0.5 cm) compared to patients with either non-alcoholic liver disease (15.0 +/- 0.6 cm, p = 0.003) or portal hypertension due to vascular occlusive diseases (16.5 +/- 2.0 cm, p = 0.006). Splenomegaly, whether assessed sonographically or clinically, is an insensitive sign of portal hypertension and its absence cannot be used as a negative predictor of the presence of portal hypertension in patients with chronic liver disease.

Adult↗

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 gamma-irradiation in the range of 500-900 rads. 9 d after gamma-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 gamma-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.

Animals↗

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.

Adult↗