Gaucher's disease associated with Hodgkin's disease

A patient with chronic adult-onset Gaucher's disease is described. The diagnosis was based on the finding of typical Gaucher cells in the spleen, liver and bone marrow associated with deficiency of glucocerebrosidase. The patient also had Hodgkin's disease, nodular sclerosis type, stage III. The patient is alive and relatively well six years after presentation, having been treated with a combination of chemotherapeutic regimens.Previously reported cases of Gaucher's disease concurrent with Hodgkin's disease are reviewed.     

Sporothrix schenckii meningitis in a farmer with Hodgkin's disease

A fatal case of chronic meningeal sporotrichosis occurring as an opportunistic infection in a patient with Hodgkin's disease is presented. A pulmonary source of infection was identified at autopsy. The diagnostic importance of the isolation of Sporothrix schenckii from cerebrospinal fluid, even if only from a single specimen, is stressed.     

Circulating immune complexes in Hodgkin's disease

Levels of circulating immune complexes (CIC) in the serum of patients with Hodgkin's disease were measured by the Raji cell radioimmunoassay. Elevated levels of immune complexes (mean value of 49 μg/ml ± 21 SE) were detected in 20 of 40 (50 per cent) untreated patients. After treatment, the level of CIC was normal (< 15 μg/ml) in 39 of 41 patients. Recurrent disease developed in two of the 39 patients with normal post-treatment levels of CIC and in one of the two patients with elevated post-treatment levels during the follow-up period of six months to six years. Elevated levels of CIC were detected in patients with Hodgkin's disease in stages I, II and III but not in stage IV. No significant correlations were found in the frequency of elevated levels of CIC or the values observed, and the presence or absence of symptoms (fever, sweats, weight loss) or the histologic subtype of the tumor. Our data indicate that the measurement of CIC by the sensitive and specific Raji cell assay may prove useful in the management of patients with Hodgkin's disease. In particular, serial measurement of the level of CIC could be employed to monitor the response to treatment and to detect recurrent diseases.     

Immune thrombocytopenia and Gaucher's disease

A 35-year-old Ashkenazi woman with Gaucher's disease was evaluated for persistent thrombocytopenia. The diagnosis of Gaucher's disease was made by bone marrow aspiration and confirmed by the determination of glucocerebrosidase levels in leukocytes and cultured skin fibroblasts. Studies of platelet-associated IgG and in vivo platelet survival demonstrated immune-mediated destruction of platelets consistent with immune thrombocytopenic purpura. A trial of prednisone had no effect on the platelet count. Total splenectomy resulted in a complete and prolonged remission. The clinical implications of Gaucher's disease and concurrent immune thrombocytopenic purpura are discussed.     

Extralymphatic Hodgkin's disease: Prognosis and response to therapy

Three hundred eighteen patients with pathologic stage IA and IB, IIA and IIB, and IIIA Hodgkin's disease who entered into Stanford University Medical Center randomized trials comparing radiation therapy alone to radiation therapy plus six cycles of adjuvant chemotherapy were evaluated. Of these, 54 patients had extralymphatic (E) lesions. There were five relapses among these patients (9 percent), not different from the 37 relapses among the remaining 264 patients (14 percent) with Hodgkin's disease confined to the lymphatic system. Actuarial survival and freedom from relapse were not significantly different for patients with or without extralymphatic disease. The survival of patients with extralymphatic disease was similar whether they received radiation therapy alone or radiation therapy plus chemotherapy.     

A nationwide outbreak of Reye's syndrome: Its epidemiologic relationship to influenza B

Between December 15 and June 30, 1974, 379 cases of confirmed Reye's syndrome were reported to the Center for Disease Control. Of these, 316 occurred during February and March 1974. A simultaneous surveillance system for influenza B indicated that this clustering of cases of Reye's syndrome correlated both temporally and geographically with influenza B outbreaks. The incidence of Reye's syndrome was higher in rural than in urban centers. Epidemiologically, two groups of cases of Reye's syndrome emerge: those which occur in older children (median age 11 years), cluster in time and geographic region, and are associated with antecedent influenza B infection; and those which occur sporadically throughout the year, are isolated in occurrence, occur in younger children (median age 6 years), and are associated with a wide variety of antecedent viral illnesses.     

The malignant potential of the dysgenetic germ cell in Klinefelter's syndrome

We report two cases of extragonadal germ cell tumors in patients with Klinefelter's syndrome and review the other cases of germ cell tumors reported in this syndrome. Especially in choriocarcinoma, the presence of Klinefelter's syndrome may be overlooked because of the similar clinical presentations and testicular histology. We recommend karyotypes be carried out in patients with germ cell tumors since the dysgenetic gonad of Klinefelter's syndrome may be important in the pathogenesis of these malignancies. Also patients with Klinefelter's syndrome should be followed closely because of their increased risk of development of germ cell tumors.     

Long-term follow-up of ovarian function in women treated with MOPP chemotherapy for Hodgkin's disease

Twenty-seven women previously treated with MOPP (mechlorethamine, vincristine, procarbazine, prednisone) chemotherapy were evaluated to determine the status of ovarian function. All patients had completed therapy a median of nine years earlier and had a median age of 30 years at the time of evaluation. Persistent amenorrhea has occurred in 11 of 24 patients (46 percent) treated with MOPP alone or MOPP plus radiation excluding the pelvis. Of patients with amenorrhea, 89 percent were older than age 25 at the time of treatment. In contrast, 80 percent of patients younger than age 25 at treatment continue to menstruate regularly. The time from diagnosis to amenorrhea was significantly shorter in the older patients (p = 0.001). Evaluation of serum gonadotropin and estradiol levels confirms ovarian failure as the cause of amenorrhea in all patients. Overall, these 27 patients have borne 13 normal children subsequent to chemotherapy. This long-term follow-up study demonstrates that chemotherapy-induced ovarian failure is age-related, that ovarian failure is often gradual in onset following the completion of chemotherapy and that, to date, the children born of women treated with this chemotherapy regimen appear to be entirely normal.     

Goodpasture's syndrome: Failure of nephrectomy to cure pulmonary hemorrhage

Two patients with Goodpasture's syndrome are described. The diagnosis was typical both on clinical and pathologic evidence. Both patients presented with pulmonary symptoms with hemoptysis and suffered from rapidly progressive and irreversible glomerulonephritis. Histologic study of the lungs in one patient demonstrated extensive intra-alveolar hemorrhage. Histologic examination of the kidneys in both patients disclosed changes of rapidly progressive glomerulonephritis with epithelial crescents. Immunofluorescent studies showed linear staining of the glomerular capillary basement membrane with (IgG) and (C′₃). Bilateral nephrectomy was carried out in both patients in an attempt to control the pulmonary manifestations. There was no improvement in the first patient and he died 2 days after the operation. The nephrectomy has not prevented recurrence of the pulmonary hemorrhage in the second patient in whom the lungs were less severely diseased; he is maintained on longterm hemodialysis, and the pulmonary disease is best controlled by corticosteroids. Bilateral nephrectomy is not always as successful as has been claimed in previous reports.     

Morbidity of staging laparotomy in Hodgkin's disease

The morbidity of exploratory laparotomy and splenectomy in Hodgkin's disease was determined at three institutions—a university hospital, a major university affiliated hospital and a large community hospital. Of the 90 patients who underwent exploratory laparotomy, 33 (37 per cent) sustained a major or minor complication within two weeks of surgery. Seventeen patients (19 per cent) sustained a minor complication and 16 patients (18 per cent) a major complication. There was no mortality. A higher complication rate occurred in patients more than 28 years of age (p = 0.01), and in patients with advanced clinical stage when age was controlled (p = 0.05). We suggest that prior to performing an exploratory laparotomy in a given patient, the necessity of the procedure be weighed against its potential hazards.     

Acquired bullous disease of the skin and solitary amyloidoma of the lung

A 70 year old black woman had a 1 year history of bullae occurring at points of trauma without preceding inflammation. She was also found to have a solitary amyloidoma of the upper lobe of the left lung and no signs of amyloidosis elsewhere. Her general health, except for mild chronic bronchitis, was good.     

Staging laparotomy and splenectomy in early Hodgkin's disease: No therapeutic benefit

In a prospective randomized study of treatment for early-stage Hodgkin's disease presenting above the diaphragm, 76 patients had staging by laparotomy (Group I) and 28 had staging by closed techniques (Group II). Treatment consisted of involved-field radiotherapy alone (44 patients), involved-field radiotherapy followed by chemotherapy (38 patients), total nodal radiotherapy atone (15 patients), or total nodal radiotherapy followed by chemotherapy (seven patients). On presentation, both groups had similar clinical features and similar treatment distribution. With similar follow-up (87 months), no significant differences in remission or survival were observed between Groups I and II: remission 59 versus 68 percent; survival 74 versus 92 percent; p value 0.27 and 0.09, respectively. Multiple areas of relapse were more frequently observed in Group I (11 of 32 had relapse) as compared with Group II (none of nine had relapse, p < 0.082). In Group I, relapse in the abdomen was observed as an isolated event or as part of disseminated relapse in 12 percent of patients compared with 3 percent (one patient) in Group II with abdominal relapse alone. Seven patients in Group I and two patients in Group II died with Hodgkin's disease. Six other patients in Group I died with complete remission of non-Hodgkin's lymphoma (one patient), leukoencephalopathy (one patient), sepsis during chemotherapy (two patients), myocardial infarction (one patient), and cerebrovascular accident (one patient). Three other patients in this group had other secondary malignancies successfully controlled (histiocytic lymphoma, squamous cell carcinoma of the cervix, and malignant schwannoma). No second primary lesions or death with complete remission were observed in Group II. Staging laparotomy with splenectomy in early-stage Hodgkin's disease did not improve the duration of remission or survival or decrease the number of abdominal relapses compared with closed staging.     

Steroid myopathy in connective tissue disease

In eight women with polymyositis (three patients), systemic lupus erythematosus (SLE) (three patients), rheumatoid arthritis (one patient) and shoulder-hand syndrome (one patient), weakness developed during high dose prednisone therapy. These women were studied using serial functional and manual muscle tests, determination of serum glutamic oxaloacetic transaminase (SGOT), creatinine phosphokinase (CPK) and serum aldolase levels, and urinary excretion of creatine. Insidious onset of weakness was characteristic. Myalgias were seen in five patients and unusual sudden weakness in two. Weakness was always most severe in the pelvic girdle muscles; there was a lesser involvement of shoulder girdle and distal muscles.Serum muscle enzyme levels were normal in all cases, but urinary creatine excretion was invariably increased and proved to be the most sensitive laboratory indicator for clinical diagnosis and for monitoring patient improvement. Serial urinary creatine excretion and serum enzyme studies were of value in differenting steroid myopathy from a flare of myositis in patients with connective tissue disease. Diagnosis and effective management were achieved by the use of readily available laboratory and clinical procedures without resorting to muscle biopsy.     

Liver cysts in patients with autosomal dominant polycystic kidney disease

Liver cysts were found in 46 (29 per cent) of 158 patients over 10 years of age with documented autosomal dominant-type polycystic kidney disease (PKD) from 62 unrelated families. Hepatic cysts were not found in any patient at risk for PKD in whom renal cysts were not detected. The prevalence of liver cysts increased with advancing age and with declining rate of glomerular filtration. Results of clinical and laboratory studies indicate that polycystic liver disease in patients with autosomal dominant-type PKD is a benign condition, rarely, if ever, causing impaired liver function or portal hypertension.     

Acquired von Willebrand's disease,platelet-release defect and angiodysplasia

A previously healthy elderly man with gastrointestinal bleeding was found to have criteria for von Willebrand's disease. The late clinical onset of the disorder and negative family studies suggest that the von Willebrand's disease may be acquired. The findings in the patient were similar to the abnormalities reported in the small number of other patients thought to have acquired von Willebrand's disease. An inhibitor of factor VIII could not be demonstrated in this patient. This patient also had platelet aggregation abnormalities that are atypical for patients with congenital or acquired von Willebrand's disease. Vascular abnormalities were also found in this patient and in several other previously described patients with von Willebrand's disease.     

Cardiac failure in Addison's disease

In an average 30 years of follow-up study, seven of 22 patients with primary adrenal insufficiency have had cardiac failure. Comparison of these seven with the 15 who remain free of this complication revealed that the former group were somewhat older and had higher incidences of unrelated cardiac disease and of nonsteroid-dependent hypertension, but that their replacement regimens, with respect to sodium supplementation and sodium-retaining steroids, were identical with the latter. Coincident with the appearance of cardiac failure, all seven patients had a decrease in sodium requirements. Adequate control of the adrenal disease was subsequently possible with elimination of mineralocorticoid support in one of the six who had initially required this therapy and a reduction in dosage in the other five. In all seven, dietary sodium supplements were no longer required. In three patients with severe failure, sodium restriction was imposed and diuretics were added, although the latter therapy has required close monitoring to avoid sodium depletion.     

Importance of anti-lung antibody in farmer's lung disease

The presence of anti-lung antibody was evaluated in 20 patients with farmer's lung disease. Antibody was found in 14. In patients with disease of less than five years' duration, there was no evidence of any significant differences in vital capacity, total lung capacity, diffusion capacity, and PaO₂ between those wtth and without antilung antibody. However, in patients with disease of longer than five years' duration, the diffusion capacity was lower in the anti-lung antibody-positive group (p < 0.05). The prevalence of abnormalities of vital capacity and diffusion capacity and flbrosis on chest roentgenograms was higher in those who had anti-lung antibody and disease of more than five years' duration. The study suggests that anti-lung antibody is present before permanent measurable physiologic abnormality occurs and may potentiate the pulmonary damage during subsequent episodes.     

Multisystem involvement in chronic liver disease. Studies on the incidence and pathogenesis

Sjögren's syndrome occurred in 37 per cent, renal tubular acidosis in 32 per cent, pulmonary diffusion defects in 26 per cent and peripheral neuropathy in 10 per cent of patients with active chronic hepatitis, primary biliary cirrhosis or cryptogenic cirrhosis. The incidence of certain other conditions determined from clinical features alone was lower; these included arthropathy in 14 per cent, thyroid disorders in 10 per cent, skin lesions in 17 per cent and colitis in 5 per cent. In the complete series of 218 patients, 125 (57 per cent) had involvement of at least one organ other than the liver, such involvement being significantly more common in those with active chronic hepatitis (63 per cent of cases) and primary biliary cirrhosis (68 per cent) than in those with cryptogenic cirrhosis (38 per cent). In a number of patients, prednisone therapy was followed by both subjective and objective improvement in the features of the multisystem involvement.No correlation could be found between multisystem involvement and the presence of mitochondrial, smooth muscle or antinuclear antibodies in the serum or with the serum levels of immunoglobulins A (IgA), M (IgM) and G (IgG). Histologie examination of the various organs disclosed dense infiltration with small lymphocytes, suggesting that delayed hypersensitivity reactions were involved in the production of tissue damage. In support of this was the demonstration of cell-mediated reactivity in vitro to salivary or renal antigens in 42 per cent of the patients with Sjögren's syndrome and in 62 per cent of those with renal tubular acidosis, respectively.These findings, together with the frequency and similar pattern of multisystem involvement in the three conditions, suggest a common pathogenetic mechanism, and disordered cellular immune reactions directed primarily against the liver could affect other organs as a result of cross antigenicity.