HLA loci predisposing to immune TTP in Japanese: potential role of the shared ADAMTS13 peptide bound to different HLA-DR.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune disorder caused by neutralizing anti-ADAMTS13 autoantibodies. In white individuals, HLA allele DRB1*11 is a predisposing factor for iTTP, whereas DRB1*04 is a protective factor. However, the role of HLA in Asians is unclear. In this study, we analyzed 10 HLA loci using next-generation sequencing in 52 Japanese patients with iTTP, and the allele frequency in the iTTP group was compared with that in a Japanese control group. We identified the following HLA alleles as predisposing factors for iTTP in the Japanese population: DRB1*08:03 (odds ratio [OR], 3.06; corrected P [Pc] = .005), DRB3/4/5*blank (OR, 2.3; Pc = .007), DQA1*01:03 (OR, 2.25; Pc = .006), and DQB1*06:01 (OR,: 2.41; Pc = .003). The estimated haplotype consisting of these 4 alleles was significantly more frequent in the iTTP group than in the control group (30.8% vs 6.0%; Pc < .001). DRB1*15:01 and DRB5*01:01 were weak protective factors for iTTP (OR, 0.23; Pc = .076; and OR, 0.23, Pc = .034, respectively). On the other hand, DRB1*11 and DRB1*04 were not associated with iTTP in the Japanese. These findings indicated that predisposing and protective factors for iTTP differ between Japanese and white individuals. HLA-DR molecules encoded by DRB1*08:03 and DRB1*11:01 have different peptide-binding motifs, but interestingly, bound to the shared ADAMTS13 peptide in an in silico prediction model.

[Disseminated cryptococcosis during ibrutinib treatment for chronic lymphocytic leukemia].

We report a case of invasive fungal infection (IFI) that ensued during ibrutinib treatment. A 79-year-old female was diagnosed with chronic lymphocytic leukemia seven years prior. She had undergone chemotherapy at the ages of 72 and 75. Subsequently, she was placed on ibrutinib treatment at the age of 79. On the 119th day after the ibrutinib treatment initiation, she was admitted to our hospital with the complaints of frequent urination and hematuria, and three days later, she died of disseminated cryptococcosis.IFIs should be considered in the event of infections that develop early after the ibrutinib treatment initiation.

[Long-term administration of brentuximab vedotin in a patient with primary cutaneous anaplastic large cell lymphoma with peripheral blood involvement with leukemic change].

We report a case of long-term administration of brentuximab vedotin (BV) for primary cutaneous anaplastic large cell lymphoma (pc-ALCL) with leukemic change. A 67-year-old man with lymphadenopathy was admitted to our hospital. Six years ago, he was diagnosed with pc-ALCL at another hospital, and complete remission was achieved with radiation therapy. We performed a biopsy of his lymph node and diagnosed the recurrence of pc-ALCL with leukemic change. Initially, CHOP and GCD regimens were ineffective; however, partial remission was achieved following BV therapy. Thus far, he has received 42 courses of BV; he has responded well to the treatment and no serious side effects have been observed.

[Marked reactive plasmacytosis accompanied by drug eruption in a patient with aplastic anemia].

A 61-year-old woman with aplastic anemia was admitted to our hospital in October 2009 because of fever and abdominal pain. She had been treated with cyclosporin A without showing any effect. On admission, uterine cancer was diagnosed and the left uterine appendages were swollen. She was treated with cefepime for febrile neutropenia without effect, and left-sided adnexitis was diagnosed. After cefepime was changed to meropenem, marked plasmacytosis was observed in the peripheral blood (23%) and bone marrow (79%) with the appearance of skin eruption. Although the plasma cells were morphologically abnormal, the cytoplasmic immunoglobulin light chain deviation was not detected by flow cytometric analysis, and M protein was not found by serum immunoelectrophoresis. She was diagnosed with reactive plasmacytosis and treated with dexamethasone. The drug eruption and plasmacytosis improved soon after starting the treatment. Although reactive plasmacytosis is observed with a variety of conditions, including infection, neoplasms, autoimmune disorders, and hemolytic anemia, it has not been reported to accompany drug eruption. Reactive plasmacytosis is sometimes not possible to distinguish from plasma cell neoplasms on morphology alone and needs to be diagnosed comprehensively by using flow cytometric analysis and immunohistochemical evaluation.

Syndrome of Inappropriate Antidiuretic Hormone Associated with Eosinophilic Granulomatosis with Polyangiitis.

A 78-year-old woman with a history of bronchial asthma presented with distal dominant sensory disturbance and weakness in the upper and lower extremities. A biopsy of the left peroneus brevis muscle showed active vasculitis with inflammation extending into muscle fascicles and fibrinoid necrosis of the vessel wall, consistent with eosinophilic granulomatosis with polyangiitis (EGPA). Despite her decreased serum osmolarity, her serum antidiuretic hormone level was not reduced, consistent with the syndrome of inappropriate antidiuretic hormone (SIADH). Intravenous and oral steroid therapy improved her neurological symptoms. Clinicians should consider EGPA as a concurrent, and potentially causative, disorder in cases of SIADH.