71/317. Hypereosinophilia with abnormal T cells, trisomy 7 and elevated TARC serum level. The idiopathic hypereosinophilic syndrome (HES) is a rare heterogeneous disorder, characterized by persistent blood eosinophilia with possible organ involvement. We describe here the case of a 20-year-old atopic male presenting chronic hypereosinophilia and eczema since childhood. Biological findings included hypereosinophilia (9.5 x 10(9)/L), hyperlymphocytosis (10.9 x 10(9)/L), polyclonal hypergammaglobulinemia and elevated IgE serum level. Flow cytometric analysis of blood lymphoid cells showed a population of CD2 CD3-CD4 TCRab-TCRgd- lymphocytes. These cells displayed a Th0/Th2 cytokine profile, and a clonal TCR rearrangement pattern. A high serum TARC level was observed. karyotype studies on blood stimulated culture or lymph nodes revealed a cellular hyperdiploid clone 47, XY, 7. To our knowledge, this chromosomal aberration has never been reported in such case. ( info) |
72/317. Pruritic urticarial papules and plaques of pregnancy (PUPPP)--a case report. Pruritic urticarial papules and plaques of pregnancy (PUPPP) is a rare dermatosis of unknown etiology that is most frequently seen in primiparas and twin/multiple pregnancies. The prognosis is favorable. We report a case of PUPPP in a primipara and review the clinical signs, differential diagnosis, possible etiologic factors, diagnosis, and therapy. ( info) |
| A 37 year-old man who developed a fatal middle cerebral territory infarct was found at autopsy, to have widespread granulomatous angiitis involving meningeal and intracranial--extracerebral vessels but not intracerebral vessels or other extra-cranial vessels. The findings are unique and overlap with those of granulomatous angiitis of the nervous system (GANS) and classic giant cell arteritis (GCA). A possible precipitant for this devastating illness was a recent chlamydia infection. The salient clinical and pathologic differences between GANS and GCA of the nervous system are discussed. ( info) |
74/317. Pseudomigraine with lymphocytic pleocytosis: a calcium channelopathy? Clinical description of 10 cases and genetic analysis of the familial hemiplegic migraine gene CACNA1A. OBJECTIVE: To report the clinical findings of 10 patients diagnosed with pseudomigraine with lymphocytic pleocytosis and the results of mutational analysis of the CACNA1A gene in 8 of these patients. BACKGROUND: Pseudomigraine with lymphocytic pleocytosis, also referred to as headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL), is characterized by episodic transient neurologic dysfunction associated with moderate to severe headache and cerebrospinal fluid lymphocytic pleocytosis. Episodes are recurrent and the condition is self-limiting. The etiology of this sporadic condition remains unknown, but the episodic nature and its ability to be triggered by angiography is somewhat reminiscent of the phenotypic features of familial hemiplegic migraine, a condition caused by mutations in the CACNA1A gene. DESIGN/methods: Utilizing retrospective chart review, we describe the clinical features of pseudomigraine with lymphocytic pleocytosis in 10 patients. Whole blood was taken from 8 patients (2 were lost to follow-up) and used for dna testing. The CACNA1A gene was screened for mutations using heteroduplex analysis and direct dna sequencing. RESULTS: Clinical features of pseudomigraine with lymphocytic pleocytosis included transient episodes of weakness, sensory and visual symptoms, aphasia, and confusion lasting minutes up to 4 hours. Sensory symptoms, typically affecting the face and arm, were the most common presentation. Localization of symptoms did not conform to vascular territories. headache was typically throbbing and most often bilateral. Genetic analysis did not identify any mutations in the CACNA1A gene. CONCLUSIONS: Similarities between familial hemiplegic migraine and pseudomigraine with lymphocytic pleocytosis include recurrent headache with reversible neurologic deficit, cerebrospinal fluid lymphocytic pleocytosis, and triggers such as angiography. Even so, heteroduplex analysis and dna sequencing failed to identify any sporadic mutations or shared polymorphisms in the exons or the intron/exon boundaries of the CACNA1A gene. These results do not support a role of the CACNA1A gene in the etiology of pseudomigraine with lymphocytic pleocytosis. ( info) |
75/317. Detection of clonal Epstein-Barr virus in malignant proliferation of peripheral blood CD3 CD8 T cells. Epstein Barr virus (EBV) dna was detected in a monoclonal proliferation of T cells in a three-year-old girl who presented with a history of fever, hepatosplenomegaly, and generalised lymphadenopathy. The disease ran a rapid, fulminant course and the patient died 11 days after presentation. Examination of the blood showed a lymphocytosis of 50 x 10(9)/l with all the cells showing the morphology of large granular lymphocytes. These cells were CD2 3 8 25 . Cytogenetic studies showed the presence of a 6q- clone. Southern blotting and hybridisation with a constant region probe for the T-cell receptor (TCR) beta chain gene showed clonal rearrangement of the TCR beta gene. Hybridisation of the Southern blot to the EBV XhoI probe revealed a clonal pattern of episomal EBV dna. Our results establish the association between clonal EBV infection to a malignant proliferation of peripheral blood CD8 T cells. ( info) |
76/317. Large granular lymphocytosis terminating in a polymorphous B-lymphocytic proliferation after low-dose cyclophosphamide therapy: a case report with necropsy findings. A 70-year-old man presented with clonal large granular lymphocytosis of T-suppressor/cytotoxic immunophenotype, neutropenia, paraproteinemia, and proneness to infection. The patient became severely leukopenic during 14 days of chemotherapy with low-dose cyclophosphamide, and remained so after discontinuation of the drug. Clinically, he was thought to have prolonged chemotherapy-induced marrow hypoplasia. At death, 16 days after the last dose of chemotherapy, autopsy confirmed bone marrow hypoplasia and revealed that well-differentiated, polymorphous, and (immunophenotypically and genotypically) polyclonal b-lymphocytes predominated in normal hematopoietic and lymphoid organs. A similar lymphoid infiltrate was intimately associated with multiple ulcers and smooth muscle necrosis in the stomach. These terminal findings resemble B-lymphoproliferative conditions described in certain forms of immune deficiency. ( info) |
| Previous reports of patients with persistent polyclonal B lymphocytosis have found associations with female sex, cigarette smoking, HLA-DR7 phenotype, and moderate elevation of peripheral blood polyclonal B lymphocytes. The presence of binucleated cells and atypical lymphocytes in the peripheral blood of these patients was highly suggestive of a viral infection, such as with the Epstein-Barr virus. We report a 47-year-old asymptomatic woman who was incidentally found to have persistent polyclonal B lymphocytosis and serum IgG against virus capsid antigen (VCA) and Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) of EBV. The presence of EBV was investigated in the peripheral blood lymphocytes from this patient by in situ hybridization and polymerase chain reaction methods. EBV dna was demonstrated in the lymphocyte fraction by polymerase chain reaction, and it was further located in lymphoid cells by in situ hybridization. These results indicate that persistent polyclonal B lymphocytosis is strongly associated with EBV. ( info) |
78/317. Demonstration of clonality, by X-linked dna analysis, in chronic natural killer cell lymphocytosis and successful therapy with oral cyclophosphamide. The expanded lymphocyte population in large granular lymphocyte (LGL)-leukemia carries the phenotypic characteristics of either cytotoxic T lymphocytes (CD3 ,CD8 ) or natural killer (NK) cells (CD3-,CD15 ). In the former subset, clonality has been demonstrated by T-cell receptor gene rearrangement studies. Since NK cells do not rearrange T-cell receptor genes, the neoplastic nature of chronic NK cell lymphocytosis has not been well defined. We used X-linked dna analysis to study the clonal nature of an expanded NK cell population in a patient with a 3-year history of relative lymphocytosis associated with anemia and neutropenia. Southern blot analysis showed no clonal T-cell receptor gene rearrangement. The majority of the circulating lymphocytes had a NK cell phenotype and demonstrated both direct NK cell-mediated cytotoxicity and antibody-dependent cellular cytotoxicity. However, the in vitro growth characteristics of these cells did not suggest that they were polyclonal expansions of normal NK cells. To determine directly the clonal origin of these cells, we performed X-linked dna analysis. Density gradient centrifugation methods were used to isolate mononuclear cells, and NK cells were positively selected by CD16-immunoconjugated magnetic beads. The dna of these cells was analyzed by restriction fragment length polymorphism-methylation strategy and showed a monoclonal pattern of X-chromosome inactivation while a polyclonal pattern was obtained in corresponding skin tissue. Treatment of the patient with oral cyclophosphamide resulted in complete hematologic remission. We conclude that chronic NK lymphocytosis may be clonal and responsive to immunosuppressive therapy. ( info) |
| Three patients infected with human immunodeficiency virus (hiv) presented with pseudotumoral splenomegaly, CD8 lymphocytosis (3.5-5.1 x 10(9)/l), and hypergammaglobulinaemia. spleen and bone marrow showed diffuse CD8 lymphocyte and plasma-cell infiltration. Amplification of the T-cell-receptor gamma chain gene did not reveal any clonal T-cell population. Phenotypic analysis showed a predominance of CD8/CD57 suppressor T cells with expression of activation markers (DR and CD38). No cytotoxic T lymphocytes specific for hiv could be detected. The three patients shared the HLA haplotype A1, B8, DR3. The association with this haplotype suggests a genetically determined host immune response to hiv. ( info) |
80/317. Extreme lymphoplasmacytosis and hepatic failure associated with sulfasalazine hypersensitivity reaction and a concurrent EBV infection--case report and review of the literature. We present an unusual case of a patient with extreme lymphoplasmacytosis and hepatic failure in association with a reaction to sulfasalazine and a concurrent Epstein-Barr virus (EBV) infection. Sulfa drugs can cause a wide range of allergic and hypersensitivity reactions and occasionally can lead to a fulminant illness. In the case under discussion the patient had hepatotoxicity, skin rash, fever, and peripheral blood atypical lymphocytosis. Initial impressions suggested the possibility of a malignant lymphoproliferative disorder. flow cytometry of peripheral blood and a bone marrow biopsy provided clear evidence for a reactive, polyclonal process as opposed to a malignant disorder. Cessation of the offending drug and administration of steroids led to dramatic improvement. This case illustrates that drug hypersensitivity reactions can be manifested by an extreme lymphocytoid leukemoid reaction. ( info) |