Cyclic hematopoiesis: human cyclic neutropenia

Human cyclic neutropenia is a relatively rare disorder of unknown etiology. Study of patients and animals with the disorder has led to important information regarding the differentiation of blood cells and control mechanisms of hematopoietic regulation. It has a world-wide distribution, occurs in both sexes, and, in about one-fourth of the patients, a family history has been obtained. While usually benign, deaths from overwhelming infections occur. In addition to cycling of neutrophils, in the majority of cases the monocytes cycle and in about one-fifth of the cases eosinophils are elevated. In a small number of patients, cycling of platelets and reticulocytes occurs. Cycles of colony stimulating factor are present. Cycles of bone marrow cells are easily demonstrable. The recent transfer of human cyclic neutropenia following allogenic bone marrow grafting confirms the hypothesis that the disorder is of bone marrow origin. The following subjects are covered in this review article: A. Definition, history, and incidence; B. Etiology, geographic distribution, mode of transmission; C. Symptoms, physical signs, diagnosis, clinical course; D. Clinical laboratory studies; E. Experimental studies; F. Prognosis; G. Treatment. It is felt that human cyclic neutropenia represents a heterogeneous group of disorders and that much remains to be learned about its cause(s).     

Small Intestine Amyloidosis Producing a Stippled Punctate Mucosal Pattern: Radiological-Pathological Correlation

A case of small intestinal amyloidosis that has a myriad punctate mucosal relief pattern of minute filling defects and barium flecks is presented with pathological correlation. Amyloidosis is added to the differential diagnosis of this radiographic small bowel appearance.     

Crohn''s Disease Associated with Cyclic Neutropenia

Crohn's disease and neutropenia unrelated to drug therapy is a rare association. We present a case of Crohn's disease associated with cyclic neutropenia. Our patient, observed over 10 yr, is unique due to the lack of recurrent bacterial infections or other associated sequelae of the neutropenic state. There was no consistent association between white blood cell cycling and exacerbations of her Crohn's disease. However, the latter did appear to worsen the neutropenic state. A clear pattern of cyclic neutropenia became apparent only when the disease was quiescent and all medications had been discontinued. We report this case for its value in pursuing clinically and therapeutically appropriate options, including surgery and drugs with neutropenic potential, in patients with Crohn's disease and, possibly, white blood cell abnormalities.     

Localized amyloidosis of the genitourinary tract: report of 5 new cases and review of the literature

Primary localized amyloidosis of the genitourinary tract is a rare entity characterized by small pseudotumors localized in the renal pelvis, ureters, or bladder. Amyloid fibrils are derived from immunoglobulin light chains, but no systemic plasma cell proliferation is detected. The clinical and radiologic features mimic urinary tract cancer, and local treatment is indicated. The prognosis is excellent in most cases, although disease recurrence is possible. We report 5 new cases of localized amyloidosis of the urinary tract, with lambda (4/5), or kappa (1/5) chain amyloid protein, involving the bladder (5/5), and the ureter and renal pelvis (1/5), with multiple, bilateral lesions in 1 case. The presenting complaint was painless hematuria in 4 cases. All cases were of primary (AL)-type amyloidosis. All patients underwent extensive investigation, and none presented any signs of generalized amyloidosis. A favorable outcome was observed in every case. We performed a comprehensive review of the literature, and summarize the data.     

Cyclic neutropenia complicated of non-Hodgkin lymphoma

This paper reports a case of non-Hodgkin's lymphoma concurrent with cyclic neutropenia. A 59-year-old man who exhibited a neutropenia at a periodicity of 14-20 days from July 1986 was diagnosed as having cyclic neutropenia, and was re-admitted to our hospital because of an abdominal tumor in April 1988. Gastroscopy revealed a Borrmann II-like elevated lesion, and abdominal CT scanning showed a low density area in the liver and swelling of the para-aortic lymph nodes. According to histological examination of the stomach and the liver, the patient was diagnosed as having non-Hodgkin's lymphoma (diffuse, medium-cell type). After completion of three courses of COP-BLAM III therapy, which was started on June 7, a partial response was achieved. However, the patient had a relapse and died on May 12, 1989. Cyclic neutropenia in this case was not considered to be due to an immunological abnormality mediated by lymphocytes, but may have been caused by an excessive response of the negative feedback mechanism due to an increase in CIA (Colony-inhibiting activity) of neutrophils. The fact that the patient's EB virus antibody titer became higher than at this initial hospitalization suggests the possible transition from chronic EB virus infection into malignant lymphoma.     

Left atrial myxoma associated with systemic AA amyloidosis

A 76-year-old woman presenting with generalized amyloidosis of the AA-type protein was found to have a left atrial myxoma. Retrospective estimation of the concentration of SAA protein, a serum precursor of AA amyloid, before and after surgical removal of the myxoma, showed that the SAA protein had disappeared after the operation. A common manifestation of myxoma is the development of a severe inflammatory syndrome that sometimes simulates rheumatic fever or bacterial endocarditis. However, to our knowledge, it has never been described in association with amyloidosis. We suggest that atrial myxoma should be added the list of neoplastic and inflammatory diseases predisposing to AA amyloidosis.     

Amyloid colitis

Amyloidosis not infrequently involves the gastrointestinal tract and may result in a variety of symptoms, including those related to impaired motility, malabsorption, and ulceration due to ischemia. This report describes the case of a 74-year-old man with systemic amyloidosis secondary to multiple myeloma, with striking gross morphologic findings involving the colon, seen at autopsy, resembling severe inflammatory bowel disease. Microscopically, the small arterioles of the lamina propria were markedly narrowed or occluded by massive deposition of amyloid, presumably leading to diffuse ischemia and mucosal necrosis, Although the radiologic appearance of this condition has been well recognized, and ischemia due to amyloidosis has been described, this case is presented to demonstrate the gross anatomic changes not illustrated in previous reviews of the subject.     

Gastrointestinal amyloidosis associated with transthyretin Phe64Ser mutation

Familial amyloidotic polyneuropathy (FAP) is a hereditary generalized amyloidosis that results from mutations in the transthyretin (TTR) gene. More then 100 mutations of TTR have been described. Corresponding to the wide variety of TTR mutations, FAP presents with diverse clinical phenotypes. TTR-Phe64Ser is a rare mutation that has previously only been described once in a Canadian family that presented with oculoleptomeningeal symptoms. We report the clinical and molecular characterization of the first described case of a TTR-Phe64Ser mutation in an African-American family with profound gastrointestinal symptoms.     

Human cyclic neutropenia transferred by allogeneic bone marrow grafting

Human cyclic neutropenia shows many features in common with the animal model of cyclic neutropenia in grey collie dogs. Until now, however, evidence was lacking that cyclic neutropenia in man as in the dog is caused by a defect in a transplantable hematopoietic stem cell. A patient is presented who, while undergoing bone marrow transplantation as treatment for acute lymphoblastic leukemia in relapse, acquired cyclic neutropenia from her histocompatible sibling donor.     

Isolation of a low-molecular-weight serum component antigenically related to an amyloid fibril protein of unknown origin.

An amyloid fibril protein of unknown origin from a patient with systemic amyloidosis has been purified to homogeneous charge and size by gel filtration and two step isoelectric focusing. From crude antisera to the initial heterogeneous fibril protein, monospecific antibodies have been obtained by immunoabsorption with the immobilized purified amyloid protein. These antibodies have been used to identify an antigenically related serum component in whole sera of patients with and without amyloidosis. Chromatography on Sephadex G-200 in phosphate buffered saline of a patient's whole serum yields a component with an apparent molecular weight of approximately 200,000. Guanidine denaturation of this high-molecular-weight serum component followed by Sephadex G-100 column chromatography in 5 M guanidine affords an antigenically reactive protein with an apparent molecular weight of about 12,500. The antigenic similarity and molecular weight of the latter protein indicates that it could act as the smallest serum precursor of the tissue fibril protein in this group of cases of amyloidosis.     

A case of primary colon amyloidosis presenting as hematochezia

Amyloidosis is characterized by a deposition of insoluble fibrils in various organs and tissues. Amyloid deposition, in the gastrointestinal track, provokes a dysfunction of the organ, due to an accumulation of fibrils, and causes a variety of clinical symptoms and endoscopic findings. Primary amyloidosis in the gastrointestinal tract is rarely reported in Korea. We experienced a case of recurrent intestinal bleeding, in a 59-year-old female patient with primary amyloidosis. A colonoscopy revealed the presence of multiple large circular ulcers. In the entire colon, diffuse nodular lesions with edema and bleeding were found. A colonoscopic biopsy established the diagnosis of amyloidosis, to the exclusion of other disease components. We concluded that the patient had localized amyloidosis. Though a definitive therapeutic strategy has not been established for localized gastrointestinal amyloidosis, the patient has been successfully treated with a high-dose of steroids and azathioprine.     

Electrophysiological study of a Portuguese case of amyloidosis with conduction disorders]

Cardiac involvement in the course of familial Portuguese amyloidosis, as apart from the other primary amyloidosis, is characterised by the early and wide-spread intracardiac conduction disorders, and the contrasting late presentation of the clinical signs. A case is presented of Portuguese amyloidosis which was typical from the viewpoint of the neurological disorders, the familial characteristics, and the positive biopsy; the main conduction defects found in primitive amyloidoses are also recalled. The patient described had for many years suffered from first degree heart block, and then presented with lipid changes with syncopal attacks which led to electrophysiological investigation of the conduction defect, no similar example of which has been found in the literature. The severity and widespread nature of the disorders which were found, together with the localisation of a sub-His block led us to implant the pacemaker. We have only found two other patients who had implants for disorders of conduction secondary to cardiac amyloidosis. Emphasis has been laid on the importance of this investigation which, when it leads to the positioning of a pacemaker, should avoid the onset of syncopal attacks and sudden death which together constitute one of the primary causes of mortality in primary amyloidosis. The length of follow-up in our case has been 14 months (April 1977).     

Sj?gren's syndrome with solitary nodular pulmonary amyloidosis]

We describe a case of limited pulmonary amyloidosis with Sj?gren syndrome. A 58-yr-old woman was referred to our hospital because of an abnormal chest radiograph (solitary small nodule) that was examined to investigate the cause of a persistent cough. A chest CT revealed a solitary small nodule in the left lower lung field. The specimens obtained by thoracoscopic surgery showed AL (kappa) amyloid deposits with lymphoplasmacytic infiltrate. Immunofixation of the serum and concentrated urine failed to demonstrate monoclonal immunoglobulins, and no amyloid deposits in the stomach were detected. She was subsequently diagnosed as having primary Sj?gren's syndrome. Nodular pulmonary amyloidosis with Sj?gren syndrome is very rare condition, and most cases present multiple nodules. As far as is known, this is the first report of a solitary nodule in pulmonary amyloidosis with Sj?gren syndrome.     

Localized Castleman's disease and nephrotic syndrome not responsive to resection plus colchicine therapy

We describe one patient with localized Castleman's disease (CD) of the mixed hyaline vascular and plasma cell type located at the mesentery of the small bowel, associated with systemic amyloidosis and nephrotic syndrome. A true nephrotic syndrome has rarely been reported in patients with CD. In the literature, it has been suggested that clinical and laboratory manifestations generally improved after surgical resection of the tumor. However, in our case, clinical and laboratory findings did not regress after operation followed by colchicine therapy.     

Conjunctival AL amyloidosis associated with a low-grade B-cell lymphoma.

A rare case of localized amyloidosis associated with a low-grade B-cell lymphoma involving the conjunctiva is described. Although infiltrating small lymphocytes and plasma cells showed little cytological atypia, molecular genetic examination revealed a prominent B-cell clonal immunoglobulin heavy chain (IgH) gene rearrangement in the tumor tissue. Immunoelectronmicroscopic examination showed immunoglobulin lambda light chain specificity in the amyloid deposit and Russell bodies in the surrounding plasma cells. We concluded that the immunoglobulin lambda light chain, produced by the tumor's differentiated plasma cells, is the precursor protein of the localized amyloidosis found in this case.     

Crohn's ileitis complicated by amyloidosis: observations and therapeutic considerations

We present a patient with clinically asymptomatic amyloidosis associated with Crohn's ileitis. A distinction should be made between immunocytic dyscrasia associated with amyloidosis (formerly primary or myeloma-associated amyloidosis) and acquired systemic amyloidosis (formerly secondary amyloidosis). We compare the natural course of amyloidosis complicating Crohn's disease with these complicating familial Mediterranean fever (FMF), and discuss the role of resection and the rationale behind colchicine therapy. Our patient is the first reported case in which colchicine therapy alone has been successful in the prophylactic treatment of amyloidosis complicating Crohn's ileitis.     

Adult-onset cyclic bicytopenia: a case report and review of treatment of cyclic hematopoiesis

A unique case of adult-onset synchronous cyclic neutropenia and thrombocytopenia occurring at six-week intervals is presented. Periods of cytopenia were associated with fever, myalgias, gastrointestinal symptoms, and mild mucocutaneous bleeding. Alternate-day steroid treatment failed to correct the periodic fluctuations in peripheral blood counts but ameliorated symptoms during cytopenia. The treatment of cyclic hematopoiesis is reviewed.     

Value of biopsy of accessory salivary glands for the diagnosis of amyloidosis

There are few reports of amyloidosis diagnosed by deliberate biopsy of accessory salivary glands. Usually, a biopsy performed for dry mouth syndrome reveals an unsuspected amyloidosis. We report the case of 2 patients with lambda-type light chain monoclonal gammapathy complicated by generalized amyloidosis and in whom biopsy of the accessory salivary glands showed signs of amyloidosis. In the first patient accessory salivary gland biopsy was performed because these glands were enlarged, and the monoclonal dysglobulinaemia was subsequently diagnosed by serum immunoelectrophoresis. In the second patient with nephrotic syndrome, renal biopsy could not be carried out owing to the presence of a renal malformation; amyloidosis was confirmed by periumbilical fat aspiration, and a systematic biopsy of accessory salivary glands also showed evidence of amyloidosis. Biopsy of accessory salivary glands seems to be a particularly simple and safe method to detect generalized amyloidosis in patients with chronic inflammatory disease or monoclonal dysglobulinaemia.     

Systemic amyloidosis in a patient with hypogammaglobulinaemia

A 49-year-old patient with an 18-year history of hypogammaglobulinaemia presented with nephrotic syndrome due to systemic amyloidosis. Recurrent infections as a consequence of an inadequate gamma-globulin substitution therapy were regarded as the main reason for the development of amyloidosis. When a high-dose intravenous immunoglobulin therapy was started, the clinical symptoms declined and the patient felt moderately well. Later the patient developed symmetrical polyarthritis clinically suggestive of rheumatoid arthritis. Although the incidence of arthritis is increased in hypogammaglobulinaemia, arthritis has not been reported in any of the few previously described patients with hypogammaglobulinaemia-associated amyloidosis. Moreover, this case provides further evidence that, in these patients, the amyloid fibrils may be of the AA type.     

Outcome of Renal Transplant in Hereditary Gelsolin Amyloidosis

Amyloid nephropathy is an unusual manifestation of hereditary gelsolin amyloidosis and may present with proteinuria and progressive renal failure. We report the first case of renal transplantation in a patient with hereditary gelsolin amyloidosis complicated by end-stage renal disease. The patient was a 44-year-old man from the Northwest of Iran who had undergone hemodialysis for 1 year. He finally received a living, unrelated renal transplant. During a 6-year posttransplant period, the patient maintained stable allograft function without proteinuria. No significant infectious or cardiac complications were noted. Although a definite conclusion cannot be reached with a single case, this report may indicate that renal transplantation can be successfully attempted in patients with hereditary gelsolin amyloidosis and amyloid nephropathy. Renal transplantation has been performed in various hereditary, primary, and secondary amyloidoses. A brief review of this topic is presented.