Cases reported "Hypersensitivity, Delayed"

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1/16. Loss of tolerance to a maternal kidney transplant is selective for HLA class II: evidence from trans-vivo DTH and alloantibody analysis.

    We studied late graft rejection in a patient who had received a kidney transplant 9-10 years earlier from his mother and who had been off all immunosuppressive drugs for 7 years at the time of graft rejection onset. The mother differed for one HLA-A (A3) and one HLA-B (B62) antigen but had only a subtype mismatch at the HLA-DR beta 1 locus (donor: DR beta 1*1104; recipient: DR beta 1*1102). A gradual rise in serum creatinine from 1.8 to 2.0 mg/dl at year 9 prompted a biopsy, which was negative for rejection (focal infiltrates but no tubulitis). Ten months later the patient's creatinine had risen to > 3.4 mg/dl, and a second biopsy revealed extensive tubulitis, cellular rejection, and glomerular sclerosis. Sonicates of donor leukocytes triggered no delayed-type hypersensitivity (DTH) response above background (PBMC only) in the patient's peripheral blood leukocytes obtained prior to year 9. A gradual recovery of antidonor DTH response between year 9 and 10 closely paralleled the change from tolerant to rejection status. Antidonor antibody was also undetectable in serum prior to year 9, but a donor-reactive antibody did develop at year 10.2 shortly after the peak of DTH response. The serum level of soluble donor HLA class I B62 antigen rose > 10-fold over prerejection level at the time of the biopsy-proven rejection, suggesting a possible trigger for both the cellular and humoral immune response. Nonetheless, we found no evidence for the development of humoral or cellular immunity to maternal HLA class I. Instead, DTH analysis of memory T cells of the patient obtained after rejection showed that a single maternal HLA DR beta 1*1104 allopeptide, differing by two amino acids in sequence from the peptide of the recipient (DR beta 1*1102), stimulated a strong memory DTH response. Similarly, we found an anti-HLA class II donor-specific antibody in serum that appeared to be crossreactive with DR beta 1*1104 and DR beta 1*1101 but not with the recipient DR beta 1*1102 antigen. The data support the idea of a profound unresponsive state at both the cellular (DTH) and humoral level toward maternal HLA class I antigens that was not reversed even during late cellular rejection, despite the release of high levels of soluble HLA class I. Furthermore, the data suggest that DTH recovery was a close correlate of the onset of rejection and this "indirect" alloresponse, like the anti-donor alloantibody response that followed, was directed not to noninherited maternal HLA-A,B antigens but to the maternal HLA DR beta 1*1104 subtype.
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2/16. Delayed hypersensitivity reaction and acute respiratory distress syndrome following infliximab infusion.

    Infliximab, a chimeric human/murine monoclonal antibody directed against the proinflammatory cytokine tumor necrosis factor alpha, is an effective therapy for Crohn's disease (CD) and rheumatoid arthritis refractory to standard medical treatment. We report a case of adult respiratory distress syndrome associated with infliximab therapy. A 33-year-old white male presented with an exacerbation of CD and was treated with his second infliximab infusion (15 months following the first infusion). Within 7 days he developed arthralgias, myalgias, and fever, followed by respiratory failure. He required intubation and mechanical ventilation. Open lung biopsy demonstrated eosinophilic pneumonia. Human antichimeric antibodies were present at high concentrations. An extensive investigation for infectious etiologies was negative. The patient was treated with intravenous corticosteroids, and fully recovered after a prolonged hospitalization. We review the infectious and immunologic complications of infliximab.
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3/16. Macular exanthema due to fumaric acid esters.

    OBJECTIVE: To report a case of an unusual skin reaction to fumaric acid esters (FAE). CASE SUMMARY: A 68-year-old white woman who was treated with FAE for 4 days for lichen planus developed generalized pruritic exanthema. This was suspected to be an allergic drug reaction to FAE, and the treatment was discontinued. After 48-72 hours, the exanthema resolved completely. An objective causality assessment revealed that the adverse drug event was probable. As skin testing for diagnostic purposes is not feasible with FAE, the drug-related origin of the exanthema was confirmed by oral rechallenge with FAE. DISCUSSION: The effectiveness of FAE in the systemic treatment of psoriasis vulgaris has been proven by controlled clinical trials. The compound has been shown to be tolerable and safe even during prolonged treatment. The most frequent adverse effects are gastrointestinal symptoms and flushing, which typically occur 4-6 hours after administration of the drug. Allergic reactions to FAE have not yet been reported. Since the patient was rechallenged with the suspected drug, we could confirm the allergic origin of the exanthema. CONCLUSIONS: The occurrence of allergic skin reaction should be considered in patients receiving treatment with FAE.
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4/16. Mechanisms responsible for delayed and immediate hemolytic transfusion reactions in a patient with anti-E Jk(b) Di(b) and anti-HLA alloantibodies.

    Immediate hemolytic transfusion reactions (IHTR) occurred in the course of delayed hemolytic transfusion reactions (DHTR). An 84-year-old man had received a blood transfusion 20 years ago. Progressive anemia developed, because of continuous bleeding from a bladder tumor. He was transfused with concentrated red blood cells (CRC) which were Rh-E antigen negative, because he had anti-E antibodies (day 0). He received CRC on day 3, and underwent resection of bladder tumor on day 6. Although crossmatch-compatible CRCs were prepared for the operation, those were not required and were kept in a refrigerator in the ward. On day 9, when a CRC kept in the ward was transfused, he suddenly had a IHTR. In order to analyze a mechanism of IHTR, the anti-Jk(b) and anti-Di(b) antibodies, anti-HLA antibodies and the concentrations of inflammatory cytokines were measured in serum samples. The anti-Jk(b) and anti-Di(b) antibodies increased prior to IHTR experienced on day 9. The concentrations of IL-6 and IL-1beta increased from day 2, while the concentration of IL-8 increased from day 7. The anti-HLA class I antibody could be detected 2 days before IHTR. Thus, the anti-Jk(b) and anti-Di(b) antibodies induced the production of inflammatory cytokines and symptoms of DHTR and IHTR. The anti-HLA class I antibody could be produced in spite of using the filer for removing leukocytes, and may take part in the induction of IHTR. Further, blood products should be transfused soon after completing a crossmatch test in patients with anti-RBC alloantibodies.
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5/16. piperacillin/tazobactam-induced paresthesiae.

    OBJECTIVE: To describe a case of a delayed-type hypersensitivity (DTH) reaction to piperacillin/tazobactam in which painful paresthesiae were a predominant feature. CASE SUMMARY: A 27-year-old man with a history of intravenous drug abuse was admitted for treatment of a pulmonary parenchymal abscess in the setting of lower-limb deep-venous thrombosis and methicillin-sensitive staphylococcus aureus bacteremia. He was treated with intravenous piperacillin/tazobactam 4.5 g 3 times daily; however, after 2 weeks of therapy, he developed symptoms (eg, fever, chills) and laboratory abnormalities (eg, white blood cell count 2.1 x 10(3)/mm3, erythrocyte sedimentation rate 63 mm/h) suggestive of a DTH reaction. This was accompanied by infusion-related painful paresthesiae. The symptoms and laboratory abnormalities resolved within 48 hours of treatment being switched to flucloxacillin. DISCUSSION: Due to the close temporal association and the absence of any other obvious explanation, we believe these paresthesiae represent an additional feature of the DTH reaction to piperacillin/tazobactam in this patient. Use of the Naranjo probability scale indicated a probable relationship between the paresthesiae and administration of piperacillin/tazobactam. CONCLUSIONS: To our knowledge, as of March 24, 2006, this is the first case in which a DTH reaction to piperacillin/tazobactam manifesting as fever, neutropenia, and thrombocytopenia has been associated with paresthesiae.
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6/16. Bilateral basal ganglia involvement in a patient with Griscelli syndrome.

    We report a 6-year-old Iranian boy with silvery-gray hair, eyelashes and the eyebrows who was admitted because of seizures and subsequent stupor. He had previous history of acute hemiparesis at 1 year of age and hepatitis-like syndrome 3 months ago. Microscopic examination of the patient's hair shaft revealed different sized clumps of melanin seen in the center of the shafts. Bone marrow aspiration revealed erythroid hyperplasia and erythrophagocytic cells. Bilateral frontal cortical and subcortical high signal lesions, dirty white matter, high signal areas in the upper pons and in both caudates and lentiform nuclei in T2 WI were the brain MRI findings of the patient. He died in the accelerated phase of Griscelli Syndrome (GS) type 2. To our knowledge we report the first case of GS from iran.
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7/16. Syngeneic leukocytes together with suramin failed to improve immunodeficiency in a case of transfusion-associated AIDS after syngeneic bone marrow transplantation.

    A 22-year-old man who underwent syngeneic bone marrow transplantation (BMT) for acute lymphoblastic leukemia acquired a human immunodeficiency virus (hiv) infection by transfusion of blood products from a donor at risk. The manifestations were acute encephalopathy together with immune thrombocytopenia in the early posttransplant period, and acquired immunodeficiency syndrome (AIDS) developed 20 months after BMT. Because he had a syngeneic donor, the possibility of reconstituting the immune system was investigated by repeated transfer of healthy syngeneic lymphocytes and by combining repeated transfer of syngeneic lymphocytes with the antiviral agent suramin to protect the infused leukocytes from being attacked by hiv. No improvement was observed clinically or in the patient's immune functions by these efforts.
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8/16. An unusual presentation of a large tumor coexisting with an unusually high nonspecific immune responsiveness. A case report.

    The authors present the case of a 40-year-old white man with an obstructing laryngeal mass. Despite considerable tumor size, results of repeated biopsies revealed widespread carcinoma in situ with chronic inflammation within the subcutaneous tissues, and only after extensive endoscopic "debulking" of the mass was a small focus of invasive carcinoma identified. Just as surprising was the patient's unusual degree of immune competence as estimated to be at least in the upper normal range and definitely much higher than that observed in the other patients with head and neck cancer routinely examined in our department. The immune responsiveness of the patient was evaluated by total lymphocyte count, in vivo skin testing, in vitro blastogenesis, interleukin-2 and interferon-gamma production. The authors postulate that these observations may constitute a rare demonstration of the ability of the immune surveillance system to contain malignancy under physiologic conditions.
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9/16. asthma, aspergilloma and anergy in a patient being treated for pulmonary tuberculosis.

    A twenty-one-year old white girl developed cavitating pulmonary tuberculosis which was complicated by nocturnal asthma, aspergilloma and anergy. In addition she developed systemic symptoms suggestive of a hypersensitivity reaction to the aspergilloma.
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10/16. Cytogenetic and functional studies of leukocytes with pelger-huet anomaly.

    A cytogenetic study was undertaken in 15 cases of Pelger-Huet (P-H) anomaly in 3 families. An enlarged short arm of chromosome 22 (22p ) was found in 14 cases, but in these families 4 cases without P-H anomaly did not show 22p in the karyotype. In P-H anomaly, delayed skin hypersensitivity reactions, levels of serum IgG, IgM and IgA, lymphocyte subpopulations, and natural killer and antibody-dependent, cell-mediated cytotoxicity activities were within normal range. The level of serum IgE, mitogen responses in peripheral blood lymphocyte and plaque-forming cell counts were also within normal range with the exception of a case with atopic eczema. Enzymatic activities, nitroblue tetrazolium reduction and phagocytic capacities of neutrophils appeared normal. Abnormalities of neutrophils in cases of P-H anomaly, as compared with normal subjects, were also negative in examinations for chemotaxis and spontaneous migration under agarose and in a membrane filter.
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