A case of generalized pustular psoriasis caused by hydroxychloroquine in a patient with systemic lupus erythematosus.

Hydroxychloroquine (HCQ) has been used to treat systemic lupus erythematosus (SLE) in Japan since 2015. We herein report a case of SLE that developed generalized pustular psoriasis (GPP) following the administration of HCQ. Twenty-one days after the HCQ treatment, a pustular rash with itching appeared on the auricle, scalp, and forearm, and spread rapidly to the face and body trunk with a high fever and arthralgia. Skin biopsy showed pustule formation under the cornified layer, neutrophil infiltration, the destruction of keratinocytes, and spongiform pustules of Kogoj. The patient was diagnosed with GPP. HCQ was immediately discontinued, the dose of prednisolone (PSL) was increased, and granulocyte and monocyte adsorption apheresis was performed. Her symptoms subsequently disappeared. Since arthralgia relapsed after the tapering of PSL, cyclosporine was added. Although single nucleotide polymorphisms (c.28C>T and c.115+6T>C) in the interleukin (IL)-36RN gene, which encodes the IL-36 receptor antagonist, have frequently been reported in GPP, these mutations were not observed in the present case. The potential development of GPP needs to be considered when administering HCQ to patients with SLE.

A case of polyarteritis nodosa with periurethralaseptic abscesses and testicular lesions.

We describe a 54-year-old man presenting with cutaneous ulcerations, livedo reticularis, numbness of the legs, and skin histological findings compatible with the diagnosis of polyarteritis nodosa (PAN). Initial treatment with 50 mg/day of prednisolone (PSL) was effective. However, the symptoms and signs recurred, and the patient developed multiple periurethral aseptic abscesses, urethra-cutaneous fistula, and testicular lesions after tapering of PSL therapy. The condition improved with PSL and cyclophosphamide administration. Since penile and testicular vasculitis could be associated with PAN, although rarely, we should carefully distinguish such an involvement from infection and malignancy.

Genetic control of T cell receptor BJ gene expression in peripheral lymphocytes of normal and rheumatoid arthritis monozygotic twins.

The amino acids encoded at the junctions of T cell receptor (TCR) V and J genes directly interact with MHC bound peptides. However, the regulation of the human TCRBJ gene repertoire has been difficult to analyze, because of the potentially complex number of BJ gene rearrangements. To overcome this problem, we developed a PCR-ELISA method to study BJ gene expression, and compared peripheral T lymphocytes from 12 pairs of monozygotic twins, including 6 rheumatoid arthritis (RA) discordant pairs, and 5 normals. Analyses of the TCRBV5, 13 and 17 gene families, which have been reported to be increased in RA patients, showed: (a) the three TCRBV transcripts have common features of BJ gene usage; (b) TCR transcripts from each TCRBV family display a distinctive BJ gene profile, which is displayed better by CD4+ than CD8+ lymphocytes; (c) the BJ gene repertoires of monozygotic twins are more similar than those of unrelated individuals; and (d) the inflammation of RA does not induce specific changes in the genetically determined pattern of BJ expression. These results indicate that the frequency of expression particular TCRBV-TCRBJ recombinants in human lymphocytes is controlled genetically, and is maintained despite the presence of a chronic inflammatory disease.

Differential expression of chemokines in synovial cells exposed to different Borrelia burgdorferi isolates.

OBJECTIVE: Lyme borreliosis is characterized by strong inflammatory reactions probably due to the presence of Borrelia burgdorferi in the joint. It has been suggested that Borrelia induces the immunological mechanisms that either can amplify the inflammatory response or can suppress it. To reveal the underlying mechanisms of chemoattraction and activation of responding leukocytes, we investigated the induction of chemokines in human synoviocytes exposed to two different B. burgdorferi sensu stricto isolates (strain Geho and B31). METHODS: Synoviocytes were exposed in vitro up to 5 days. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to assess the relative chemokine mRNA expression of RANTES/CCL5, SDF-1alpha/CXCL12 alpha, SDF-1beta/CXCL12 beta, MCP-1/CCL2, MCP-2/CCL8, IL-8/CXCL8 and MIP-1alpha/CCL3, and enzyme-linked immunosorbant assay (ELISA) was used to assess the protein expression of RANTES, SDF-1, MCP-1, and MIP-1alpha in the culture supernatant. RESULTS: MCP-1 gene expression was not changed by strain B31 but MCP-1 gene expression along with protein concentration was suppressed by strain Geho. Both strains induced RANTES mRNA and protein concentration. SDF-1 gene expression was suppressed, whereas protein concentrations were unchanged by both strains. IL-8 gene expression was unchanged by using strain Geho but significantly upregulated by strain B31. Both strains induced MCP-2 mRNA expression. MIP-1alpha mRNA expression was induced, but chemokine concentration was suppressed by both strains. CONCLUSION: This study suggests that the orchestra of chemokines plays an important role in the immunopathogenesis of early Lyme arthritis.

Favorable outcomes with tacrolimus in two patients with refractory interstitial lung disease associated with polymyositis/dermatomyositis.

Two cases of progressive interstitial lung disease associated with polymyositis/dermatomyositis are presented. Both patients were refractory to conventional therapy with high-dose corticosteroids, cyclosporine, and intermittent pulse cyclophosphamide, and thus a therapeutic trial of tacrolimus was instituted. Tacrolimus was markedly effective in achieving subjective, laboratory and radiographic improvement in both patients.

Comparative characteristics of mu chain and alpha chain transcripts expressed by individual tonsil plasma cells.

Plasma cells (PCs) are one of the two major cell types generated during germinal center reactions. To test the hypothesis that PCs express a unique repertoire of immunoglobulin (Ig) genes resulting from intensive antigenic stimulation and selection, the mutational pattern and distribution of V(H) gene segments within 178 transcripts amplified from individual IgM and IgA secreting tonsil PCs were analyzed. The results demonstrated that both mu and alpha transcripts expressed repertoires with limited diversity. Moreover, both mu and alpha transcripts were heavily mutated, with a significantly increased mutational frequency noted for alpha compared to mu transcripts (5.0 x 10(-2) vs 1.8 x 10(-2), P<0.001). In addition, both mu and alpha transcripts showed significantly greater targeting of mutations to RGYW motifs (purine/guanine/pyrimidine/A or T) compared to memory B cells. Finally, clonally expanded cells were detected in alpha but not mu PC compartments. These results indicate that antigen driven stimulation and selection shape the entire expressed PC repertoire, but the impact is greater in alpha expressing PCs.

Emphysematous pyelonephritis successfully treated with nephrectomy and granulocyte colony-stimulating factor.

A 58-year-old woman developed diabetic ketoacidosis and emphysematous pyelonephritis caused by Escherichia coli. She was successfully treated with nephrectomy, antibiotics, and recombinant human granulocyte colony-stimulating factor (rhG-CSF). RhG-CSF therapy may be an effective adjunct for diabetic patients with severe infection, even when neutropenia is not present.

[Two cases of lupus nephritis having a high titer of anti-(histone-DNA) complex antibody without IgG anti-dsDNA antibody].

IgG antibody specific to double-stranded DNA (dsDNA) has been recognized as a predictive indicator of the renal involvement in systemic lupus erythematosus. However, we recently experienced two cases of overt lupus nephritis without IgG anti-dsDNA antibody. In both cases, high titers of antibody to the histone dimer (H2A-H2B)-dsDNA complex were detected. They responded well to the corticosteroid therapy, with a cytotoxic agent in one case, and the titers of anti-(histone-DNA) antibody was decreased along with the improvement of proteinuria. Based on the recent reports suggesting a pathogenic role of this antibody in lupus nephritis, we suggest that measurement of the anti-(histone-DNA) antibody is necessary in lupus nephritis patients, especially when IgG anti-dsDNA antibody is not detectable.

[Essential thrombocythemia in pregnancy].

A 30-year-old woman was admitted to our hospital because of thrombocythemia during pregnancy. Her leukocyte count was 10,000/microliters, Hb was 11.7 g/dl, and platelet count 181.9 x 10(4)/microliter. Bone marrow aspirate showed an increase in megakaryocytes (255/microliters). Both Ph1 chromosome and bcr rearrangement were negative. She was diagnosed as having essential thrombocythemia (ET) with pregnancy, and was treated with aspirin (150 mg/day). Her pregnancy was uneventful, but she was readmitted because of overterm pregnancy. A caesarean section was performed, and a healthy male infant weighing 3,672 g was delivered, with a platelet count of 25.5 x 10(4)/microliter. However, the uterine was atonic, and atonic hemorrhage occurred. Supravaginal hysterectomy was performed. Subsequently, intrabdominal gross hemorrhage occurred, but the bleeding was halved by platelet transfusion. Microscopic examination showed uterine infarction. We suggest that platelet count should be reduced by means of plateletpheresis or interferon-alpha throughout pregnancy with ET.

[A refractory case of adult-onset Still's disease].

We report here a case of adult-onset Still's disease (AOSD), who finally responded to a combination of cyclophosphamide (CPA) and gold sodium thiomalate (GST) after two years of active disease. A 23-year-old man having continuous high fever with skin rash, polyarthralgia and increased serum ferritin, was diagnosed as AOSD, and oral corticosteroid was initially effective. His symptoms recurred one year later without clinical improvement to increased dosage of steroid. He was admitted to our hospital with pericarditis and pleural effusion but did not respond to either intravenous (i.v.) pulse steroid therapy, methotrexate (MTX) or high dose i.v. gamma-globulin. He was partly responsive to monthly i.v. injection of CPA, but clinical symptoms did not completely subside and hyperferritinemia persisted. GST, initiated in combination with CPA, however, was successful to induce complete remission. MTX has recently been reported to be efficacious to steroid-resistant AOSD, but CPA and gold compounds might be useful to refractory case of AOSD.

[A refractory case of relapsing polychondritis].

We report here a case of relapsing polychondritis (RPC), who responded to salazosulfapyridine (SASP) after 1.5 years of active disease. A 15-year-old girl having chondritis of bilateral auricles, nose and respiratory tract, ocular inflammation, cochlear and vestibular dysfunction and seronegative polyarthritis was diagnosed as RPC, and oral corticosteroid was initially effective. She was admitted to our hospital with obstructive tract chondritis and was refractory to any of the treatment such as intravenous (i.v.) pulse steroid therapy, i.v. pulse cyclophosphamide (CPA), oral intermittent methotrexate (MTX) and high dose i.v. gamma globulin. Although she was partly responsive to oral cyclosporine A (CsA), but clinical symptoms did not completely subside. SASP, initiated in combination with oral corticostreroid and CsA, however, was successful not only to show steroid sparing effect but also to induce complete remission. SASP might be useful to refractory case of RPC.

[A case of Takayasu's arteritis with ulcerative colitis diagnosed by carotodynia and MRI findings].

We experienced a case of Takayasu's arteritis (TA) with ulceritive colitis (UC) having the onset of carotodynia, not accompanied by ischemic symptoms. MRI findings of the neck demonstrated a thickening of the bilateral carotid artery walls. The patient was treated by prednisolone with a marked improvement in both clinical symptoms and MRI findings. The patient had a unique HLA haplotype reported to correlate with both TA and UC. Carotodynia is an early but pathognomonic symptom of TA and MRI is helpful for the early diagnosis of TA.

Human peripheral blood dendritic cells and monocyte subsets display similar chemokine receptor expression profiles with differential migratory responses.

Human antigen presenting cells (APC) found in peripheral blood are considered to be precursors that have been released from the bone marrow and are in transit to the peripheral tissues. These APC populations include myeloid dendritic cells (mDC), plasmacytoid DC (pDC) and monocytes (Mo). To assign specialized functional roles and stages of development for APCs, CD33 expressing APC subsets were examined for their capacity to respond to chemokines. Three major CD33(+) subsets including CD33(bright)CD14(bright) Mo, CD33(bright)CD14(-) CD11c(+) mDC and CD33(dim)CD14(-) pDC were present. Dendritic cells subsets and Mo expressed low levels of CC and CXC receptors, but distinctive chemokine receptor expression profiles were not observed. The percentage of cells expressing a particular chemokine receptor varied from donor to donor and over time in the same donor. Myeloid DC and Mo but not pDC migrated toward CXCL12 in a concentration dependent manner. Monocytes and pDC, but not myeloid DC, were attracted by high concentrations of CXCL10. All CD33(+) subsets migrated in a concentration dependent manner toward CCL19, but responded less robustly to CCL21. CCL20 was not chemoattractant for any population. Despite the finding that APC did not exhibit unique surface chemokine receptor expression patterns, they exhibited differential migration to CXCL12, CXCL10 and CCL21 but not to CCL20 or CCL19.

Lack of correlation between chemokine receptor and T(h)1/T(h)2 cytokine expression by individual memory T cells.

Chemokine and chemokine receptor interactions may have important roles in leukocyte migration to specific immune reaction sites. Recently, it has been reported that CXC chemokine receptor (CXCR) 3 and CC chemokine receptor (CCR) 5 were preferentially expressed on T(h)1 cells, and CCR3 and CCR4 were preferentially expressed on T(h)2 cells. To investigate chemokine receptor expression by T(h) subsets in vivo, we analyzed cytokine (IL-2, IL-4 and IFN-gamma) and chemokine receptor (CXCR3, CXCR4, CCR3, CCR4 and CCR5) mRNA expression by individual peripheral CD4(+) memory T cells after short-term stimulation, employing a single-cell RT-PCR method. This ex vivo analysis shows that the frequencies of cells expressing chemokine receptor mRNA were not significantly different between T(h)1 and T(h)2 cells in normal peripheral blood. To assess a potential role of in vivo stimulation, we also analyzed unstimulated rheumatoid arthritis synovial CD4(+) memory T cells. CXCR3, CXCR4, CCR3 and CCR5 expression was detected by individual synovial T cells, but the frequencies of chemokine receptor mRNA were not clearly different between T(h)1 and non-T(h)1 cells defined by expression of IFN-gamma or lymphotoxin-alpha mRNA in all RA patients. These data suggest that chemokine receptor expression does not identify individual memory T cells producing T(h)-defining cytokines and therefore chemokine receptor expression cannot be a marker for T(h)1 or T(h)2 cells in vivo.

Mixed connective tissue disease associated with multicentric Castleman's disease.

We describe a 60-year-old woman who developed mixed connective tissue disease (MCTD) associated with multicentric Castleman's disease (MCD) and Crow-Fukase syndrome (CFS). She showed HLA DR-4 antigen and an abnormal X chromosome (47,XXX). The serum interleukin-6 (IL-6) level was markedly increased and IL-6 mRNA was detected in enlarged lymph node cells. After prednisolone was administered, her IL-6 level decreased and the symptoms of MCTD, MCD, and CFS all improved. Thus, IL-6 may be involved in the modification of the pathologic condition in this patient.