Myelodysplastic syndrome with clonal eosinophilia accompanied by eosinophilic pulmonary interstitial infiltration

We report a case of de novo myelodysplastic syndrome with clonal eosinophilia (MDS-Eo) and eosinophilic pulmonary interstitial infiltration, confirmed by autopsy. Cytogenetic study using Giemsa banding identified 47,XY,+1,der(1;7)(q10;p10),+8 in the marrow cells. Simple Giemsa staining revealed the same chromosomal aberration in metaphase spreads with eosinophilic granules, indicating the clonal proliferation of eosinophils. To our knowledge, our case is the 6th reported case of MDS-Eo with cytogenetically confirmed clonal eosinophilia, and the first autopsy of MDS-Eo. A review of the literature combined with our findings suggests that this type of chromosomal aberration might be involved in the as yet unknown pathogenesis of MDS-Eo.     

Parvovirus B19-associated haemophagocytosis in Evans syndrome: aplastic crisis accompanied by severe thrombocytopenia

Summary. A 36-year-old man who had been treated for Evans syndrome (ES) developed an aplastic crisis caused by acute human parvovirus B19 (HPV) infection. Profound thrombocytopenia (8·0 × 10⁹/l) followed with a sudden increase in platelet-associated IgG (PAIgG) (1376·9 ng/10⁷ plts). Bone marrow examination revealed a considerable number of haemophagocytic histiocytes without any disturbance of megakaryopoiesis. To our knowledge this is the first case of aplastic crisis with virus-associated haemophagocytosis in a patient with ES, which provides an interesting insight into the mechanisms for thrombocytopenia in HPV infection.     

Myelodysplastic syndrome accompanied by Addison's disease and multiple autoimmune phenomena: steroid therapy resolved cytopenias and all immune disorders.

We report here a patient with myelodysplastic syndromes (MDS), which was complicated with several autoimmune disorders and asymptomatic immunologic abnormalities. An 82-year-old woman with refractory anemia (RA) rapidly developed thrombocytopenia with the appearance of symptoms such as purpura, fatigue, anorexia, and weight loss. Furthermore, clinical examinations revealed that she also had Addison's disease, rheumatoid arthritis, and autoimmune hematological diseases such as thrombocytopenia and hemolytic anemia. However, the cytopenia and all autoimmune disorders were remarkably improved after she received steroid therapy.     

Etanercept-induced lupus accompanied by hemophagocytic syndrome

Hemophagocytic syndrome (HPS) is a severe, potentially life-threatening disorder characterized by an excessive activation of macrophages, such as may occur in the setting of lupus. A 62-year-old Japanese woman treated with etanercept for rheumatoid arthritis developed persistent fever, cytopenia, coagulopathy, and hyperferritinemia. Simultaneously, lupus-like features including pleuritis, hypocomplementemia, and positive autoantibodies were observed. She was diagnosed with HPS related to etanercept-induced lupus, and underwent immunosuppressive therapy with successful recovery. To our knowledge, this is the first case of etanercept-induced lupus accompanied by HPS. This case suggests that HPS should be considered as a complication during TNF-α inhibitor therapy.     

Autoimmune neutropenia accompanied by Tolosa-Hunt syndrome

A 47-year-old woman presented with severe neutropenia accompanied by diplopia and orbital pain. Her bone marrow was normal except for the absence of segmented neutrophils. Because the administration of granulocyte colony-stimulating factor (G-CSF) at a dose of 1 microgram/kg/day was not sufficiently effective and neutropenia developed, the patient was admitted to our hospital. Physical examination revealed painful ophthalmoplegia and hypoalgesia in the first region of trigeminal nerve, suggestive of Tolosa-Hunt syndrome. Severe neutropenia was observed in both peripheral blood and bone marrow, together with mild anemia and thrombocytopenia. The life span of red cells and platelets was shortened. High PAIgG levels, a positive Coombs test, and a positive test for anti-NA1 antibody suggested that blood cells were being destroyed by an autoimmune mechanism. Corticosteroid hormone therapy preceded by the administration of G-CSF at 5 micrograms/kg/day was effective for both neutropenia and in improving the patient's neurological findings.     

Management of Evans syndrome

Evans syndrome is an uncommon condition defined by the combination (either simultaneously or sequentially) of immune thrombocytopenia (ITP) and autoimmune haemolytic anaemia (AIHA) with a positive direct antiglobulin test (DAT) in the absence of known underlying aetiology. This condition generally runs a chronic course and is characterised by frequent exacerbations and remissions. First-line therapy is usually corticosteroids and/or intravenous immunoglobulin, to which most patients respond; however, relapse is frequent. Options for second-line therapy include immunosuppressive drugs, especially ciclosporin or mycophenolate mofetil; vincristine; danazol or a combination of these agents. More recently a small number of patients have been treated with rituximab, which induces remission in the majority although such responses are often sustained for <12 months and the long-term effects in children are unclear. Splenectomy may also be considered although long-term remissions are less frequent than in uncomplicated ITP. For very severe and refractory cases stem cell transplantation (SCT) offers the only chance of long-term cure. The limited data available suggest that allogeneic SCT may be superior to autologous SCT but both carry risks of severe morbidity and of transplant-related mortality. Cure following reduced-intensity conditioning has now been reported and should be considered for younger patients in the context of controlled clinical trials.     

Myelodysplastic syndrome accompanied by i(17) (q10) anomaly following pure red cell aplasia and transient myeloproliferative stage

A 71-year-old man was given a diagnosis of pure red cell aplasia (PRCA) in May 1995. However, immunosuppressive agents, including prednisolone, azathioprine, and cyclosporin A, were not effective, and he required frequent red cell transfusions. In September 1995, leukocytosis and thrombocytosis developed (peaking at 10,100/microliter white cells and 98.1 x 10(4)/microliter platelets, respectively, in November 1996). Conversely, the patient's peripheral blood count began to decrease in July 1996, and pancytopenia progressed thereafter i(17) (q10) chromosomal abnormality of bone marrow cells was detected in November 1996. The patient was readmitted due to the progression of thrombocytopenia (1.2 x 10(4)/microliter). His bone marrow has 16.6% blasts, and a diagnosis of myelodysplastic syndrome (MDS) was made. The patient died in November 1997. His hematological state demonstrated significant changes in a relatively short period and severe hypoerythropoiesis and eosinophilia of the bone marrow persisted throughout the clinical course. These findings suggested that a common deranged stem cell was the origin of 3 different states; PRCA, chromic myeloproliferative disorder, and MDS. The i(17) (q10) anomaly may have caused the acute proliferation of blasts and pancytopenia.     

Young's syndrome accompanied by medullary sponge kidney

A 33-year-old man was admitted to our division for further evaluation of repeated fever and purulent sputa of more than 10 years duration. Based on clinical symptoms, chest roentgenograms, bronchograms, seminal examination, testicular biopsy specimen and electron micrograph of cilia from the left main bronchial mucosa, the diagnosis of Young's syndrome was made. A drip infusion myelogram, which was performed because of a persistent hematuria, revealed bilateral medullary sponge kidney, suggesting the involvement of this hereditary disorder in Young's syndrome.     

Laurence-Moon-Biedl syndrome accompanied by congenital hepatic fibrosis

A 33 year old woman with mental deficiency, retinitis pigmentosa, obesity, and parental consanguinity (heredity) was diagnosed as having Laurence-Moon-Biedl syndrome. She also had diabetes mellitus, slight hepatic dysfunction, and hepatomegaly. Liver biopsy showed perilobular fibrosis and bile duct proliferation with cystic dilatation; these findings are consistent with those of congenital hepatic fibrosis.     

Myelodysplastic syndrome with vasculitic manifestations

Pirayesh A, Verbunt RJAM, Kluin PHM, Meinders AE, De Meijer PHEM (Leiden University Hospital, Leiden, The Netherlands). Myelodysplastic syndrome with vasculitic manifestations (Case Report). J Intern Med 1997; 242 : 425–31.
Vasculitis in patients with the myelodysplastic syndrome (MDS) is a rare phenomenon. We describe a patient who presented with necrotic lesions of his toes, which proved to be the result of immune complex mediated vasculitis. This unusual combination of vasculitis and MDS prompted us to review the literature. Forty-four cases of vasculitis in association with MDS were found. The pathogenesis of the vasculitis in MDS remains speculative, although several reports suggest an immunological mechanism. The temporal relationship could not be determined in 20 (45%) of reported cases. The prognosis of these patients appears to be worse than in patients with MDS without vasculitis. Steroids were used in 41 (93%) of the reported cases. Our patient did not receive any drug therapy, nevertheless his necrotic lesions improved within a few weeks.     

Myelodysplastic syndromes with nephrotic syndrome

It is sometimes reported that the immunological abnormalities in myelodysplastic syndromes (MDS) induce autoimmune disease (i.e., acute systemic vasculitic syndrome, chronic cutaneous vasculitis, polyneuropathy, relapsing polychondritis, and steroid-responsive pulmonary disorders). We investigated the clinical features of patients with MDS accompanied by nephrotic syndrome. We enrolled 125 patients with MDS who were admitted between January 1979 and May 1996 in this study. The renal function was assessed based on the laboratory data and the findings at the physical examination. The diagnoses of nephrotic syndrome and glomerular disease were established when 24-hr urinary excretion was more than 3.5 g and serum total protein was less than 6.0 g/dl, and when the 24-hr protein excretion was more than 1.5 g. Five patients (4%) had glomerular disease, and three (2.4%) had nephrotic syndrome. Of the five patients with glomerular disease, two had refractory anemia (RA), and three had chronic myelomonocytic leukemia (CMMOL). Three of the total 11 patients with CMMOL were diagnosed as having nephrotic syndrome. Among the CMMOL patients, those with nephrotic syndrome showed higher absolute monocyte numbers than did those without nephrotic syndrome (8830 +/- 4677/microl vs. 3061 +/- 2887/microl, P = 0.03). One CMMOL patient was treated with VP-16 and hydroxyurea. As the white blood cell count in this patient decreased, the 24-hr urine protein excretion and the serum tumor necrosis factor alpha level decreased. The relationship between nephrotic syndrome and CMMOL was not clear. High monocyte count and the serum cytokines in MDS patients may play a partial role in the evolution of glomerulonephritis, and CMMOL may be closely related to nephrotic syndrome.     

Myelodysplastic syndrome presenting as acquired ichthyosis

Ichthyosis is a cutaneous keratinization disorder that can either be congenital or acquired. Acquired ichthyosis has been reported in association with a variety of neoplastic, autoimmune, and infectious diseases. We report the case of a 68-year-old woman who presented with generalized ichthyosis as the first manifestation of myelodysplastic syndrome. This is the first fully described case of such an association in the English literature.     

Myelodysplastic syndrome associated with trisomy 2

Clinical course and cytogenetic analysis suggest that myelodysplasia (MDS) is one step in a multistep model of malignant transformation of haematopoietic stem cells to acute myeloid leukaemia (AML). We report a further case of MDS associated with trisomy 2, and comment on the significance of the cytogenetic abnormality, which as a sole abnormality only occurs in MDS, but is found in combination with other chromosomal abnormalities in AML. Previous reports on balanced and unbalanced chromosomal abnormalities associated with therapy related MDS and therapy related AML suggest that trisomy 2 is an early chromosomal abnormality in leukaemogenesis.     

Myelodysplastic syndrome associated with polymyalgia rheumatica

A 69-year-old man was referred to us because of severe pain in both girdles. A diagnosis of polymyalgia rheumatica was made, and low-dose prednisolone therapy (20 mg/d) was started. The patient's muscle pain disappeared after 3 weeks. After 5 months of therapy, pancytopenia became prominent. A marrow aspirate smear showed hypercellularity, trilineage dysplasia, and 7% blasts. The clinical diagnosis was myelodysplastic syndrome, subtype refractory anemia with excess of blasts. In elderly patients presenting with polymyalgia rheumatica, an underlying hematologic malignancy should always be looked for when the disease demonstrates clinical signs inconsistent with typical polymyalgia rheumatica.     

Myelodysplastic syndrome in children and adolescents

Myelodysplastic syndromes (MDS) are clonal disorders characterized by ineffective hematopoiesis and subsequent frequent development of acute myeloid leukemia (AML). In children and adolescents, MDS are uncommon disorders, accounting for less than 5% of hematopoietic malignancy, with great heterogeneity in presentation and clinical course. The genetic changes predisposing children to MDS are largely obscure. Monosomy 7 is the most common chromosomal abnormality, often occurring as a sole abnormality. The recent pediatric modification of the World Health Organization (WHO) classification has greatly facilitated the diagnostic process. Refractory cytopenia (RC) is the most common MDS subtype in children, occurring in about half of all MDS cases. There is consensus that the relationship between MDS with increased blast count and de novo AML is better defined by biological and clinical features than by blast count. Because monosomy 7 is the only chromosomal abnormality strongly suggestive of MDS, children presenting with a low blast count and other chromosomal aberrations or normal karyotype must be closely observed before a diagnosis of MDS can be established. With an increasing number of children surviving primary cancer with chemotherapy or radiation therapy, the incidence of secondary therapy-related MDS is rising. The MDS risk is also increased in patients with inherited bone marrow failure disorders; this relationship provides valuable insights into MDS biology. Allogeneic hematopoietic stem cell transplantation (HSCT) from a matched related or suitable unrelated donor is the choice for most children with MDS and can rescue a large proportion of patients.