Tatsuhiko Wada

Brain MRI in patients with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus

Background Manifestations in neuropsychiatric systemic lupus erythematosus (NPSLE), especially active diffuse NPSLE syndromes, are some of the most difficult complications of the disease. For the evaluation and the diagnosis of central nervous system manifestations, including NPSLE, MRI is a very useful tool to detect the various abnormalities. However, the relationship between brain MRI findings and clinical variables has not yet been clarified in patients with diffuse NPSLE. Objectives The aim of this study is to investigate the pathogenesis of diffuse NPSLE, by comparing various parameters such as serum autoantibodies and cytokines in cerebrospinal fluid (CSF) with abnormal findings revealed on brain MRIs in patients with diffuse NPSLE. Methods Fifty-three patients with diffuse NPSLE admitted to our University Hospital from 1992 to 2012 were exhaustively enrolled in this study. Their medical charts and brain MRI scans were reviewed. The relationship of MRI abnormalities with various parameters was analysed. Results As many as 25 of 53 patients (47.2%) had abnormal MRI findings. MRI findings improved after treatment in 10 of 17 patients for whom follow-up studies were available. MRI abnormalities were not correlated with age at the onset of diffuse NPSLE. However, the disease duration of SLE was significantly longer in patients with abnormal MRI findings (p=0.0009). MRI abnormalities were not significantly associated with serum autoantibodies. However, there were significant elevations of the CSF protein level (p=0.0106) and the CSF interleukin 6 level (p=0.0225) in patients with abnormal MRI findings. Patients with MRI abnormalities showed significantly higher overall mortality (p=0.0348). Conclusions The results revealed that MRI abnormalities in diffuse NPSLE might be heterogeneous with regard to their reversibility. These data also indicate that patients with diffuse NPSLE and MRI abnormalities have more severe inflammation in the central nervous system related to the activity of diffuse NPSLE, as evidenced by poorer prognosis.

Reversible focal neurological deficits in systemic lupus erythematosus: Report of 2 cases and review of the literature

We report two cases presenting focal neurological deficits with high intensity lesions in fluid attenuated inversion recovery (FLAIR) images on brain magnetic resonance imaging (MRI), which almost completely improved by corticosteroid therapy. Marked elevation of cerebrospinal fluid IL-6 was also noted when these patients showed neurological deficits. As far as we explored, there have been thirteen published case reports of systemic lupus erythematosus patients with reversible focal neurological deficits. The neurological symptoms varied from case to case, but could be attributed to the lesions on MRI scans. The completely reversible feature of neurological manifestations as well as MRI findings on corticosteroid therapy is distinct from any other disorder, including cerebrovascular disease and demyelinating syndrome, in the 1999 American College of Rheumatology nomenclature. Therefore, we propose that reversible focal neurological deficits should be added to the 1999 nomenclature and classification and case definitions.

Efficacy of tacrolimus against Churg-Strauss syndrome in a patient with myasthenia gravis

Dear Sir: Churg-Strauss syndrome (CSS) is characterized by pulmonary and systemic small-vessel necrotizing vasculitis, and/or extravascular granulomas, eosinophilia and tissue infiltration by eosinophils, occurring in individuals with asthma and often allergic rhinitis or sinusal polyposis. We report the case of a myasthenia gravis (MG) patient who developed CSS and in whom tacrolimus was effective against the eruption of CSS. The patient was a 79-year-old woman diagnosed with MG and asthma 8 years previously who had initially been treated with prednisolone (PSL) 50 mg per os (p.o.) every other day and whose dose had been reduced to PSL 5 mg p.o. every other day. However, because her osteoporosis became more severe, 6 months previously, a switch had been made from PSL to tacrolimus 3 mg daily, and her symptoms had continued to remain under control. Because her blood eosinophil count had recently risen in the absence of any precipitating cause, the increase was suspected of being drug-induced and tacrolimus was stopped. However, when she broke out in a rash 2 weeks later, a drug eruption was suspected, and she was referred to our department. Physical examination showed widespread purpura on her lower legs (Fig. 1a). Laboratory test revealed hypereosinophilia (7.82 9 10/l) with elevated IgE, 901 IU/ml (normal up to 173), and high titers of rheumatoid factor, 82 IU/ml (normal 0–10). Myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) was negative and anti-acetylcholine receptor antibody showed an increased value of 48 nmol/l (normal up to 0.2). Skin biopsy showed necrotizing vasculitis with a marked eosinophilic infiltration. CSS was diagnosed, and when treatment with tacrolimus 3 mg daily was resumed, the eruption almost completely resolved in 1 week (Fig. 1b). CSS is rare, with prevalence of 10.7–13 per million inhabitants [1], whereas the prevalence of MG is 50 per million inhabitants [2]. The exact etiology of CSS is unclear, but an autoimmune process is suggested based on the presence of T cell and eosinophil activation. Although the number of cases has been very small, there have been reports of associations between CSS and autoimmune diseases; however, this is the first report of a case in which there was an association between CSS and MG. The reason for the association between the two diseases in our patient is unknown, but it is very possible that their association was coincidental. Skin lesions occur in 40–75% of patients of CSS [3]. Palpable purpura, often necrotic, on the legs and feet is the most frequent of these manifestations, seen in half of the patients with skin involvement. Various cutaneous manifestations can also be found including petechiae, erythema multiform-like lesions, urticarial wheals, vesicles, ulceration, papules, cutaneous and subcutaneous nodules and livedo reticularis. Tacrolimus was effective in our patient, and ours is the first case in which tacrolimus has been effective. Tacrolimus is a macrolide antibiotic with immunosuppressive properties, which, on molecular basis, is 100 times more potent than that of cyclosporine A (CsA). The most possible mechanism is its ability to inhibit the activation of T lymphocytes. Compared with CsA, the adverse reactions of hypertrichosis and gingival S. Niiyama (&) Y. Amoh K. Katsuoka Department of Dermatology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan e-mail: sniiyama@aol.com

Transverse myelitis extended to disseminated encephalitis in systemic lupus erythematosus: Histological evidence for vasculitis

A 42-year-old woman was admitted due to systemic lupus erythematosus complicated with glomerulonephritis and pulmonary hypertension. During the treatment for these complications, she presented motor paresis and sensory loss caused by transverse myelitis. In spite of methyl prednisolone pulse therapy, she further developed acute confusional state due to disseminated encephalitis and fell into respiratory arrest. On laboratory examination, elevation of anti-NR2 antibodies in serum as well as in cerebrospinal fluid was noted. Although she recovered from the disseminated encephalitis after extensive treatment with high doses of corticosteroid and intravenous cyclophosphamide, she suddenly died of pulmonary hypertension. Autopsy findings confirmed the presence of liquefaction necrosis in the entire circumference of the whole spinal cord along with intimal hyperplasia and obliteration of the small arteries, accompanied by mononuclear cell infiltration and disruption of internal elastic lamina. It is therefore most likely that our patient developed longitudinal transverse myelitis through spinal cord vasculitis, which extended to brainstem and brain parenchyma, leading to the development of disseminated encephalitis.

Evaluation of Renal Adverse Effects of Combination Anti-retroviral Therapy including Tenofovir in HIV-infected Patients

PURPOSE In order to maintain plasma HIV-RNA concentration in HIV-infected patients, below the detection limit combination anti-retroviral therapy (cART) are used. Although the nucleoside/nucleotide reverse transcriptase inhibitor, tenofovir disoproxil fumarate (TDF) is a first-line drug commonly used, it is associated with renal dysfunction. Nevertheless, only few clinical studies have focused on TDF in combination with new anti-HIV drugs, including the protease inhibitor (PI) darunavir (DRV), or the integrase strand transfer inhibitor (INSTI) raltegravir (RAL). Here we report the influence of such cART involving TDF on renal function. METHODS We retrospectively investigated 68 patients under cART that included TDF between November 2004 and May 2012. We used hospital records to establish each patients background and characteristics, CD4 cell count, plasma HIV-RNA concentration, drug combinations, renal function, and anti-retrovial therapy history. RESULTS In all patients who had received cART, the plasma HIV-RNA concentration had fallen to less than 40 copies/mL by week 24 after the start of the therapy, and an increase in the CD4 cell count was observed. For each drug used in combination with TDF, the plasma HIV-RNA concentration and CD4 cell count showed a similar trend. After week 12, the estimated glomerular filtration rate (eGFR) had significantly decreased in all patients. The eGFR was significantly lower in those received PI on week 24 and in those received INSTI on week 12. The eGFR was significantly reduced in PI group who received atazanavir + ritonavir (ATV/RTV) on week 60. The eGFR in the DRV/RTV group tended to decrease. The eGFR in the PI and ATV/RTV group was significantly lower than in the efavirenz (EFV) group on week 96. CONCLUSION It selecting drugs to include in combination therapy of HIV-infected patients, consideration should be given to the risk of renal dysfunction. There is a need to monitor renal function when TDF is combined with ATV/RTV, DRV/RTV or RAL.

Detection of Streptococcus agalactiae by immunochromatography with group B streptococcus-specific surface immunogenic protein in pregnant women

BACKGROUND Infection with Streptococcus agalactiae (Group B streptococcus: GBS) is a significant cause of morbidity and mortality in neonates. Screening for GBS is mainly done by culture-based methods, but a reliable result may take several days to obtain and culture is difficult to perform at institutions without a laboratory. We evaluated an immunochromatography method for rapid detection of GBS-specific surface immunogenic protein (Sip) using anti-Sip monoclonal antibodies. MATERIALS AND METHODS A total of 377 cervical and vaginal swabs collected during weeks 35-37 of gestation were inoculated into GBS medium F and incubated. Growth of microorganisms and production of red/orange pigment were assessed by observation. Then culture extracts were subjected to immunochromatography and were also inoculated onto chromID Strepto B (STRB) medium, after which isolates were serotyped and characterized by PCR. RESULTS Of the 377 samples, 54 (14.3%) were positive for GBS by immunochromatography after incubation in GBS medium F. On the other hand, GBS was isolated from 58 (15.4%) of the 377 samples by culture with GBS medium F and STRB medium. Ten of the 58 isolates were non-pigmented and 4 of these were not detected by immunochromatography. The sensitivity, specificity, positive predictive value, and negative predictive value of immunochromatography were 93.1% (54/58), 100% (319/319), 100% (54/54), and 98.8% (319/323), respectively. CONCLUSIONS Immunochromatography was comparable to culture on STRB medium for detecting GBS, indicating that this method could be used clinically for GBS screening in pregnant women even at small institutions.

A very rare case of primary meningococcal arthritis in an adult male

We report here a very rare case of primary meningococcal arthritis of the knee joint without clinical features associated with meningococcemia, meningitis, or meningococcal complications. The patient suffered from diabetes mellitus and had experienced two episodes of joint trauma. Intravenous infusion of ampicillin/sulbactam for 18 consecutive days was successful.

FRI0327 Brain mri findings in patients with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus

Background Neuropsychiatric manifestations in systemic lupus erythematosus (NPSLE) are one of the most difficult complications of the disease, especially diffuse psychiatric/neuropsychological syndromes (diffuse NPSLE). For the evaluation and the diagnosis of central nervous system manifestations including NPSLE, magnetic resonance imaging (MRI) is a very useful tool to detect the various abnormalities in brain such as acute or chronic changes in cerebrum, cerebellum and brain stem. However, the relationship between brain MRI findings and clinical variables has not been clear in patients with diffuse NPSLE. Objectives The aim of this study is to investigate the association of various parameters with abnormal findings on brain MRI in patients with diffuse NPSLE. Methods Fifty-three patients with diffuse NPSLE admitted to Kitasato university hospital and Teikyo university hospital from 1992 to 2012 were exhaustively enrolled in this study. The medical charts were reviewed along with the findings on brain MRI scans. The relationship of MRI abnormalities with various parameters was analyzed. Results Of 53 patients (37 acute confusional state, 6 psychosis, 3 anxiety disorder, 12 mood disorder and 6 cognitive dysfunction), 25 patients [47.2%] had abnormal MRI findings, including 5 patients with cortical lesions, 18 patients with white matter lesions, 3 patients with meningeal lesions, 1 patient with lesions in cerebellum and brainstem, and 1 patient with cerebral hemorrhage. There was no significant association of MRI abnormalities with certain types of manifestation indiffuse NPSLE. MRI findings were partially or completely ameliorated after treatment in 10 of 17 patients in which follow-up MRI scans were available. The presence of MRI abnormalities was not correlated with the ages at the onset of diffuse NPSLE. However, the disease duration of SLE was significantly longer in patients with abnormal MRI findings (p=0.0284). The presence of MRI abnormalities was not significantly associated with serum anti-DNA, anti-Sm anti-RNP, anti-ribosomal P, or anti-phospholipid antibodies. Of note, IL-6 level in cerebrospinal fluid was significantly elevated in patients with abnormal MRI findings (figure left, p=0.0233). Finally, patients with MRI abnormalities showed significantly higher overall mortality (figure right, HR: 0.223, 95% CI: 0.0601-0.901, p=0.0348). Image/graph Conclusions These results indicate that those patients with diffuse NPSLE who showed MRI abnormalities have more severe disease, as evidenced by higher cerebrospinal IL-6 and poorer prognosis. The data also suggest that MRI abnormalities in diffuse NPSLE might be heterogeneous with regard to their reversibility. References Hirohata S, et al. 2009 Nov;28(11):1319-23. Luyendijk J, et al. Arthritis Rheum. 2011 Mar;63(3):722-32. Steup-Beekman GM, et al. Ann Rheum Dis. 2012 Dec 19. Disclosure of Interest: None Declared