Sachiko Onishi

Dermatomyositis associated with thyroid cancer: a paraneoplastic syndrome?

We have read the recent article by Fujita et al. [1] “Dermatomyositis associated with thyroid cancer” with great interest. They reported the removal of the coexisting thyroid cancer in a patient with corticosteroid resistant dermatomyositis (DM) resulted in improvement of DM. We have experienced two cases of DM associated with thyroid cancer, both of them responded to conventional immunosuppressive treatment without removal of thyroid cancer.

Fluorodeoxyglucose positron emission tomography/computed tomography for diagnostic imaging in relapsing polychondritis with atypical manifestations.

A50-year-old Japanese woman was referred to our hospital with persistent cough, sore throat, and arthritis. She had been having bronchial asthma with recurrent exacerbations for 5 months. Acute epiglottitis of unknown etiology had occurred 3 months previously and had caused respiratory compromise, requiring prednisolone (40 mg/d). She developed a persistent cough, sore throat, and arthritis of the left wrist and left ankle when prednisolone was tapered to 20 mg/d. On admission, her joint pain had subsided, but loud stridor was audible. Laboratory findings were as follows: C-reactive protein, 4.29 mg/dL; rheumatoid factor, negative; anticyclic citrullinated peptide antibody, negative; antinuclear antibody, negative; antineutrophil cytoplasmic antibodies, negative; and antiYtype II collagen antibody, positive at a titer of more than 104 U/mL (which was the upper limit of the detection range). Computed tomography (CT) of the chest showed thickening of the tracheal walls (Fig. 1) and stenoses of both main bronchi (Fig. 2). Fluorodeoxyglucose positron emission tomography combined with CT (FDG-PET/CT) revealed prominent uptake of tracer in the trachea (Fig. 3) and main

Simultaneous Pneumatosis Cystoides Intestinalis and Pneumomediastinum in a Patient with Systemic Sclerosis

To the Editor: Interstitial lung disease (ILD) is a common pulmonary manifestation in patients with systemic sclerosis (SSc). Pneumomediastinum occasionally develops in patients with connective tissue diseases (CTD) and ILD, but is rare in SSc1,2,3. Although gastrointestinal (GI) involvement is common in patients with SSc, pneumatosis cystoides intestinalis (PCI), which is characterized by the presence of gas-filled cysts in the intestinal wall, is a rare complication4. We encountered a patient with SSc who showed simultaneous occurrence of pneumomediastinum and PCI. A 61-year-old Japanese woman had been diagnosed with SSc 6 years earlier based on the findings of proximal scleroderma, positive antinuclear antibody (1:640 with nucleolar and homogeneous patterns), positive anti-Scl-70 antibody (1:16), and ILD. Fingertip ulceration had developed 4 years before. Prednisolone (20 mg/day) had been started 2 years before for her skin sclerosis. She had gradually lost her appetite and her weight had declined by 15 kg over the previous 6 months. She was admitted to our division because of … Address correspondence to Dr. Nagashima; E-mail: naga4ma{at}jichi.ac.jp

Urinary β2-microglobulin as a sensitive marker for haemophagocytic syndrome associated with collagen vascular diseases

activation, as well as the release of MMPs. ET-1 may lead to NFB stimulation and may subsequently stimulate the production of pro-inflammatory cytokines like IL-6, IL-8 and TNF[10]. The use of an oral ET dual receptor antagonist in our patient led to a rapid remission of ischaemia. This fast and sustained response had probably been achieved by potent vasodilatation. The reversal of the obstructive vasculitis documented by MRA might also at least partially be related to bosentan. The blockade of ET might have caused a down-regulation of pro-inflammatory cytokines and cells by a mechanism mentioned earlier. Corticosteroids were already terminated 4 weeks after the start of the bosentan therapy. Now, 9 months later, there is no evidence of reoccurrence of vasculitis. Bosentan might, therefore, be responsible for sustained remission. This could be interpreted as further piece of evidence of its anti-inflammatory potential in this case. In conclusion, we think that bosentan, in this individual patient, exhibited compelling vasodilatatory and anti-inflammatory effects leading to a rapid and sustained clinical improvement of the ischaemia, probably achieved by antagonization of endothelin. Bosentan might, for this reason, be regarded as therapeutic alternative in ischaemic complications caused by vasculitic syndromes resistant to standard treatment regimes.

Low level of seroconversion after a novel influenza A/H1N1/2009 vaccination in Japanese patients with rheumatoid arthritis in the 2009 season

We examined change in the antibody titre against pandemic influenza A/H1N1/2009 before and after vaccination in Japanese patients with rheumatoid arthritis. This observational study was conducted with the participation of five hospitals in Japan. A total of 89 patients with rheumatoid arthritis were included in this study. The seroprotection and seroresponse rates to vaccination with the pandemic influenza A/H1N1/2009 vaccine were analysed. The seroprotection rates prior to the vaccination were 5.6% in the Japanese patients with rheumatoid arthritis. The seroprotection rates after subcutaneous vaccination were 55.1%. The seroresponse rate after subcutaneous vaccination was 50.6% in the patients with rheumatoid arthritis. Both the seroprotection and seroresponse rates obtained after the vaccination with the pandemic influenza A/H1N1/2009 vaccine were low in Japanese patients with rheumatoid arthritis. We should realise that a vaccination against this newly emerged influenza virus may protect only half of the Japanese patients with rheumatoid arthritis in a real world.

Healthcare-associated infections in rheumatology in Japan

Prospective observational study was performed to elucidate the incidence and characteristics of healthcare-associated infections in a university hospital for rheumatology care. In this study, a total of 1,226 patients were prospectively enrolled between March 2004 and February 2006 and between April 2008 and December 2008. Healthcare-associated infection was defined as an infection developing after the third day of admission to the rheumatology ward. We detected the following 54 healthcare-associated infections in 49 patients: respiratory tract infection, 14 cases; Clostridium difficile infection, 2 cases; urinary tract infection, 4 cases; bloodstream infection, 9 cases; skin infection, 2 cases; reactivation of latent cytomegalovirus infection, 6 cases; herpes zoster infection, 5 cases; Candida infection, 7 cases; others, 4 cases. The incidence rate of respiratory tract infection was the highest. Methicillin-resistant Staphylococcus aureus was the causative bacterium in 21% of respiratory tract infections cases. Bloodstream infection due to the insertion of a catheter and opportunistic infection by a latent virus were also occurred commonly. Respiratory tract infection, bloodstream infection and opportunistic infection by a latent virus were the most common causes of healthcare-associated infection in rheumatology. It is important to pay more attention to healthcare-associated infection.

Antiribosomal-P protein antibodies are associated with proliferative glomerulonephritis more strongly than with membranous glomerulonephritis in Japanese patients with systemic lupus erythematosus.

Although the relationship between antiribosomal-P protein antibodies (anti-P) and lupus nephritis has been reported previously, it is still controversial [1]. Recently, do Nascimento et al. [2] reported that anti-P was a potential serologic marker for lupus membranous nephritis. On the other hand, Bertolaccini et al. [3] reported that anti-P did not discriminate membranous types of nephritis. The significant association of anti-P with membranous nephritis has not been confirmed thus far. To study further this association, we investigated with which types of lupus nephritis anti-P are associated in Japanese patients with systemic lupus erythematosus (SLE). The study group comprised 86 patients with SLE [79 women and 7 men; mean ± standard deviation (SD) age 34.2 ± 13.9 (range 13–74) years; mean ± SD SLE disease duration 4.3 ± 5.9 (range 0–38) years) who underwent renal biopsy and for whom frozen serum samples were available at the time of biopsy. All patients fulfilled the revised American College of Rheumatology criteria for the classification of SLE [4]. Renal histological findings were recorded according to the 2004 criteria for the classification of lupus glomerulonephritis [5]. To avoid confounding factors, patients who had class V lupus nephritis in combination with classes III or IV were excluded from this study. Among 86 patients with a biopsy-documented diagnosis of lupus nephritis, 48 had proliferative nephritis (nine class III and 39 class IV), 25 had membranous nephritis (class V), and 13 had mesangial nephritis (class II). Anti-P were measured by enzyme-linked immunosorbent assay (ELISA) using recombinant ribosomal P0 protein as an antigen, as previously described [6]. This assay sensitivity is 96%, and the cutoff value of anti-P titers is 3.68 arbitrary U/ml. Anti-P were present in 52 of 86 patients (60.5%). Positive frequencies of anti-P in Chinese and Japanese (36–42%) patients have been reported to be higher than those in Caucasian populations (13–20%) [6, 7]. Chindalore et al. [1] reported the high positive frequency of anti-P (75.0%) in US patients with active lupus nephritis and the disappearance of anti-P in periods of disease remission. The high positive frequency of anti-P revealed in this study might be derived from the ethnic differences and the presence of active lupus nephritis. Analysis of histological patterns of lupus nephritis did not reveal a higher frequency of class V nephritis in patients with anti-P compared with those without anti-P [11 of 52 patients with anti-P (21%) vs. 14 of 34 patients without anti-P (41%); P = 0.203 by chi-square test]. This nonassociation was even more evident when comparing the frequency of anti-P in patients with class V nephritis [11 of 25 patients (44.0%)] and patients with other histological subclasses (II, III, and IV) [41 of 61 patients (67.2%)] (P = 0.040 by Fisher’s exact test). The frequencies of T. Yoshio (&) S. Onishi S. Minota Division of Rheumatology and Clinical Immunology, School of Medicine, Jichi Medical University, 3311 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan e-mail: takuyosh@jichi.ac.jp

Acute acalculous cholecystitis in systemic sclerosis

Dear Editor, Acute acalculous cholecystitis (AAC), which is inflammation of gallbladder without evidence of calculi, accounts for 2–15% of all cases of acute cholecystitis [1]. Systemic sclerosis (SSc) often causes gastrointestinal complications, but involvement of the gallbladder or biliary tree is rare [2]. We describe a patient who had SSc with multiple digital ulcers and developed AAC during treatment with low-dose oral morphine hydrochloride. A 57-year-old Japanese woman was admitted to our hospital with multiple digital ulcers. She had been diagnosed with idiopathic thrombocytopenic purpura at the age of 27 years. Splenectomy was performed, and then received glucocorticoid treatment for about 10 years. At the age of 40 years, stiffness of the hands, arthralgia and cutaneous sclerosis developed. Antinuclear antibody was positive (1:2,560), as was anti-Scl-70 antibody (1:16), and dilatation of the esophagus was observed. Skin biopsy (from her forearm) supported the diagnosis of SSc. Interstitial lung disease was not detected. Treatment with prednisolone (30 mg/day) was started to control her cutaneous sclerosis. Recurrent multiple digital ulcers occurred from the age of 53 years, leading to amputation of the second and third fingers of the right hand and the fifth finger of the left hand. On admission, she was taking prednisolone (5 mg/day), nifedipine (20 mg/day), beraprost sodium (120 lg/day), and diclofenac (75 mg/day). She had digital ulcers on the extensor surface of the proximal interphalangeal joint of the right fourth finger and the distal interphalangeal joint of the left third finger, as well as interdigital ulcers between the fourth and fifth toes of the right foot. Because diclofenac was unable to control her pain, oral morphine hydrochloride was added at 20 mg/day and then increased to 25 mg/day. Intravenous administration of cefazolin (2 g/day) and alprostadil emulsion (10 lg/day) was started. Her pain was relieved by morphine. Twelve days later, fever (maximum 39 C) and mild right flank pain developed. C-reactive protein was 15.2 mg/dl and the leukocyte count was 13,600/ll (71% neutrophils). Total bilirubin, hepatic transaminases, alkaline phosphatase, and c-glutamyltransferase were all within the normal range. Antineutrophil cytoplasmic antibody for myeloperoxidase and proteinase-3, anti-b2 glycoprotein I antibody, and IgG and IgM anticardiolipin antibodies were all negative. Contrast enhanced computed tomography of the abdomen demonstrated an enlarged gallbladder with no stones. The gallbladder wall was 5 mm thick on abdominal ultrasonography, which confirmed the diagnosis of AAC. Ampicillin/ sulbactam (6 g/day) and melopenem (2 g/day) were administered. However, fever and dull pain persisted, and Murphy’s sign became positive, so open cholecystectomy was performed on day 15 for suspected gallbladder perforation. The gallbladder was filled with green bile juice, and multiple ulcers were observed on its inner surface. Histopathological examination of the resected specimen showed multiple ulcers with hemorrhage, some of which extended to the subserosal layer. Increased fibroblast proliferation was also observed in the subserosal layer. These findings were compatible with a combination of acute and chronic cholecystitis. Culture of the bile juice was negative. Her postoperative course was uneventful. However, her right fourth finger and right fifth toe were eventually amputated. T. Nagashima (&) T. Imai K. Matsumoto S. Onishi S. Takatori M. Iwamoto S. Minota Division of Rheumatology and Clinical Immunology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan e-mail: naga4ma@jichi.ac.jp