Kenzo Kaji

Clinical Correlations With Dermatomyositis-Specific Autoantibodies in Adult Japanese Patients With Dermatomyositis: A Multicenter Cross-sectional Study

OBJECTIVE To clarify the association of clinical and prognostic features with dermatomyositis (DM)-specific autoantibodies (Abs) in adult Japanese patients with DM. DESIGN Retrospective study. SETTING Kanazawa University Graduate School of Medical Science Department of Dermatology and collaborating medical centers. Patients A total of 376 consecutive adult Japanese patients with DM who visited our hospital or collaborating medical centers between 2003 and 2008. MAIN OUTCOME MEASURES Clinical and laboratory characteristics of adult Japanese patients with DM and DM-specific Abs that include Abs against Mi-2, 155/140, and CADM-140. RESULTS In patients with DM, anti-Mi-2, anti-155/140, and anti-CADM-140 were detected in 9 (2%), 25 (7%), and 43 (11%), respectively. These DM-specific Abs were mutually exclusive and were detected in none of 34 patients with polymyositis, 326 with systemic sclerosis, and 97 with systemic lupus erythematosus. Anti-Mi-2 was associated with classical DM without interstitial lung disease or malignancy, whereas anti-155/140 was associated with malignancy. Patients with anti-CADM-140 frequently had clinically amyopathic DM and rapidly progressive interstitial lung disease. Cumulative survival rates were more favorable in patients with anti-Mi-2 compared with those with anti-155/140 or anti-CADM-140 (P < .01 for both comparisons). Nearly all deaths occurred within 1 year after diagnosis in patients with anti-CADM-140. Conclusion Dermatomyositis-specific Abs define clinically distinct subsets and are useful for predicting clinical outcomes in patients with DM.

Common and Distinct Clinical Features in Adult Patients with Anti-Aminoacyl-tRNA Synthetase Antibodies: Heterogeneity within the Syndrome

Objective To identify similarities and differences in the clinical features of adult Japanese patients with individual anti-aminoacyl-tRNA synthetase antibodies (anti-ARS Abs). Methods This was a retrospective analysis of 166 adult Japanese patients with anti-ARS Abs detected by immunoprecipitation assays. These patients had visited Kanazawa University Hospital or collaborating medical centers from 2003 to 2009. Results Anti-ARS Ab specificity included anti-Jo-1 (36%), anti-EJ (23%), anti-PL-7 (18%), anti-PL-12 (11%), anti-KS (8%), and anti-OJ (5%). These anti-ARS Abs were mutually exclusive, except for one serum Ab that had both anti-PL-7 and PL-12 reactivity. Myositis was closely associated with anti-Jo-1, anti-EJ, and anti-PL-7, while interstitial lung disease (ILD) was correlated with all 6 anti-ARS Abs. Dermatomyositis (DM)-specific skin manifestations (heliotrope rash and Gottron’s sign) were frequently observed in patients with anti-Jo-1, anti-EJ, anti-PL-7, and anti-PL-12. Therefore, most clinical diagnoses were polymyositis or DM for anti-Jo-1, anti-EJ, and anti-PL-7; clinically amyopathic DM or ILD for anti-PL-12; and ILD for anti-KS and anti-OJ. Patients with anti-Jo-1, anti-EJ, and anti-PL-7 developed myositis later if they had ILD alone at the time of disease onset, and most patients with anti-ARS Abs eventually developed ILD if they did not have ILD at disease onset. Conclusion Patients with anti-ARS Abs are relatively homogeneous. However, the distribution and timing of myositis, ILD, and rashes differ among patients with individual anti-ARS Abs. Thus, identification of individual anti-ARS Abs is beneficial to define this rather homogeneous subset and to predict clinical outcomes within the “anti-synthetase syndrome.”

Anti-NXP2 autoantibodies in adult patients with idiopathic inflammatory myopathies: possible association with malignancy

Objectives Myositis-specific autoantibodies (MSAs) are useful tools for identifying clinically homogeneous subsets and predicting prognosis of patients with idiopathic inflammatory myopathies (IIM) including polymyositis (PM) and dermatomyositis (DM). Recent studies have shown that anti-NXP2 antibody (Ab) is a major MSA in juvenile dermatomyositis (JDM). In this study the frequencies and clinical associations of anti-NXP2 Ab were evaluated in adult patients with IIM. Methods Clinical data and serum samples were collected from 507 adult Japanese patients with IIM (445 with DM and 62 with PM). Eleven patients with JDM, 108 with systemic lupus erythematosus, 433 with systemic sclerosis and 124 with idiopathic pulmonary fibrosis were assessed as disease controls. Serum was examined for anti-NXP2 Ab by immunoprecipitation and western blotting using polyclonal anti-NXP2 Ab. Results Seven patients (1.6%) with adult DM and one (1.6%) with adult PM were positive for anti-NXP2 Ab. Except for two patients with JDM, none of the disease controls were positive for this autoantibody. Among eight adult patients with IIM, three had internal malignancies within 3 years of diagnosis of IIM. Another patient with DM also had a metastatic cancer at the diagnosis. All of the carcinomas were at an advanced stage (stage IIIb–IV). Conclusions While less common than in juvenile IIM, anti-NXP2 Ab was found in adult IIM. Anti-NXP2 Ab may be associated with adult IIM with malignancy.

Autoantibodies to small ubiquitin-like modifier activating enzymes in Japanese patients with dermatomyositis: comparison with a UK Caucasian cohort

Dermatomyositis (DM) is a heterogeneous disease with varying degrees and time courses of skin eruptions, myositis and internal organ involvement.1 Increasing evidence has demonstrated that myositis-specific autoantibodies (MSAs) are closely associated with distinct clinical subsets.2 Recently, Betteridge et al 3 ,4 reported a novel MSA against small ubiquitin-like modifier activating enzyme (SAE) in DM patients. In this study, we detected this autoantibody in a Japanese DM cohort and assessed its clinical correlations. We screened 456 consecutive Japanese patients with DM (11 children, 445 adults); 373 fulfilled the criteria of Bohan and Peter5 ,6 and the remaining 83 fulfilled Sontheimers criteria for clinically amyopathic DM (CADM).7 Controls included 62 patients with polymyositis, 108 with systemic lupus erythematosus, 433 with systemic sclerosis and 124 with interstitial lung disease (ILD) alone. The institutional review board approved the study protocol. Immunoprecipitation assays were performed as described.8 Protein A-agarose beads preincubated with sera were incubated with 35S-methionine-labelled or unlabelled K562 cell extracts. Immunoprecipitants were fractionated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, followed by autoradiography or …

Reduced red blood cell velocity in nail-fold capillaries as a sensitive and specific indicator of microcirculation injury in systemic sclerosis

OBJECTIVE To assess red blood cell velocity in finger nail-fold capillaries using video capillaroscopy in patients with SSc and other collagen diseases. METHODS This study included 127 patients with SSc as well as patients with SLE (n = 33), DM/PM (n = 21), RA (n = 13) and APS (n = 12), and 20 healthy subjects. Red blood cell velocity was evaluated using frame-to-frame determination of the position of capillary plasma gaps. RESULTS The mean red blood cell velocity was significantly decreased in patients with SSc compared to healthy controls (63.0% reduction) and patients with other conditions. Mean blood velocity was similar between patients with dcSSc and lcSSc. Importantly, even SSc patients with normal or non-specific nail-fold video capillaroscopic (NVC) patterns or a scleroderma early NVC pattern exhibited a significantly lower red blood cell velocity compared to healthy controls (51.7 and 61.4% reduction, respectively) or patients with other conditions, despite normal or mild capillary changes. Patients with the scleroderma active and late NVC pattern showed a more decreased blood velocity (65.5 and 66.2% reduction, respectively). This reduced blood velocity was significantly associated with NVC findings, including capillary ramification and capillary loss. Although remarkably reduced velocity was observed in SSc patients with intractable digital ulcers (72.1% reduction), it was significantly improved by lipo-prostaglandin E(1) (lipo-PGE(1)) infusion. CONCLUSION Our results suggest that reduced blood velocity is a hallmark of SSc. Furthermore, measurement of red blood cell velocity may be useful in evaluating therapeutic effects on microcirculation.

Intractable genital ulcers from herpes simplex virus reactivation in drug‐induced hypersensitivity syndrome caused by allopurinol

Background  Drug‐induced hypersensitivity syndrome (DIHS/DRESS) is a severe adverse systemic reaction. Reactivation of human herpesvirus (HHV) family members other than HHV‐6 has been reported in patients with DIHS. Reactivation of HHV family members is generally characterized by increased serum antibody titers against the virus. By contrast, clinical symptoms caused by viral reactivation are relatively rare.

Multiple small pulmonary emboli associated with transient antiphospholipid syndrome in human Parvovirus B19 infection

Antiphospholipid antibodies (aPL) have been reported to occur in several conditions other than antiphospholipid syndrome, including infections. We herein report the case of a 21-year-old Japanese woman with Parvovirus B19 infection, who developed multiple pulmonary emboli associated with aPL, a lupus anticoagulant and IgM anticardiolipin antibody. Eight weeks later, antiphospholipid antibodies spontaneously disappeared and normal pulmonary flow was observed. Considering the high prevalence of Parvovirus B19 infection, we should be aware of thrombosis associated with transient aPL antibodies in this infectious disease.

Dermatomyositis with anti-OJ antibody

A subset of patients with polymyositis (PM)/dermatomyositis (DM) has autoantibodies to aminoacyl-tRNA synthetases (ARS). The most common anti-ARS antibody is anti-Jo-1 (histidyl-tRNA synthetase) antibody, which is positive in up to 20% of patients with PM/DM [1]. In addition to anti-Jo-1 antibody, seven autoantibodies to ARS have been identified, including anti-OJ (isoleucyltRNA synthetase) antibody [1]. A 49-year-old Japanese woman presented with a 2-month history of erythema involving her eyelids, shoulders, hands, upper chest and back, and lateral thighs with associated fatigue and fever. On examination, proximal muscle weakness in her neck and lower limbs was detected. Dermatological assessment was notable for heliotrope rash involving periorbital skin, Gottron’s lesions over both extensor and flexor surfaces of metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints (Fig. 1), mechanic’s hands, periungual erythema, nail fold bleeding, edematous erythema across shoulders, anterior chest and back, and thighs with some ulceration. Laboratory examinations showed increases in aldolase (11.4 U/ ml, normal: \6.1) and KL-6 (622 U/ml, normal: \500). Creatine kinase (CK; 149 IU/l) and SP-D (33.5 ng/ml) were within normal ranges. Anti-nuclear antibodies (ANA) were negative by indirect immunofluorescence. Anti-Jo-1 antibody was not detected by enzyme-linked immunosorbent assay. Electromyographic examination demonstrated myogenic pattern on iliopsoas muscle, compatible with myositis. Pulmonary function tests were within normal limits. Chest computed tomography showed ground glass opacities in bilateral lower lung fields. Histological examination of skin biopsy specimens demonstrated epidermal atrophy, liquefaction degeneration, dermal edema, and a perivascular lymphocytic infiltrate in the superficial dermis (Fig. 2). An extensive search detected no underlying malignancy. Based on these findings, she was diagnosed with DM and interstitial lung disease (ILD). Oral prednisone 60 mg/day (1 mg/kg per day) was administered. Fever shortly resolved, and her skin lesions and muscle weakness were gradually improved. Immunoprecipitation assay was conducted, and the antibody recognizing OJ antigens was identified in the serum of the present case (Fig. 3). Since DM patients with anti-ARS antibody often fail to fully respond to oral corticosteroid and manifest recurrent flares during the tapering of corticosteroid, the patient was administered with oral cyclosporine 150 mg/day. At 3 months after the initiation of cyclosporine, prednisone was successfully tapered to 20 mg/day and aldolase and KL-6 were decreased to normal ranges. S. Noda Y. Asano (&) Z. Tamaki M. Hirabayashi M. Yamamoto T. Takekoshi T. Hoashi M. Sugaya S. Sato Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan e-mail: yasano-tky@umin.ac.jp

Anti-p155/140 antibody-positive dermatomyositis with metastasis originating from an unknown site.

Dermatomyositis (DM) is a systemic inflammatory myopathy with characteristic cutaneous manifestations (a heliotrope rash, Gottrons papules, paronychial erythema and nailfold bleeding) and is often associated with interstitial lung disease and internal malignancy. Thus far, some autoantibodies specific for myositis have been discovered, including antibodies to aminoacyl-tRNA synthetases (ARS), anti-Mi-2 antibodies, anti-CADM 140 antibody, anti-p155/140 antibody and others (1-3). The various autoantibody-positive subgroups of DM vary in their clinical features. Of these myositis-specific autoantibodies, the anti-p155/140 antibody is a 155-kDa reactive nuclear protein relevant to cancer-associated DM (1, 4-8). However, the frequency of malignancies in patients with anti-p155/140 antibody is undefined because no large epidemiological studies have been undertaken. We describe here a patient with anti-p155/140 antibody-positive DM who had a poorly differentiated metastatic adenocarcinoma; however, the primary tumour could not be identified despite comprehensive examination.

Drug eruption due to intravesical instillations of both epirubicin and mitomycin C.

We present the first patient to develop drug eruption due to intravesical instillations of both epirubicin and mitomycin C. A 58‐year‐old‐man underwent transurethral resection (TUR) for superficial bladder carcinoma followed by instillations of intravesical chemotherapy. Immediately after TUR, the first instillation of epirubicin was performed. Two days after the first instillation, the patient developed generalized erythema of the face, trunk, upper and lower limbs. Two days after the second instillation, the patient developed severe generalized erythema and was diagnosed as having drug eruption due to intravesical instillations of epirubicin by the dermatologist. Instead of epirubicin, mitomycin C was instilled 2 weeks postoperatively. Two days after the first instillation of mitomycin C, the patient again developed severe generalized erythema and was diagnosed as having drug eruption due to intravesical instillation of mitomycin C. Drug eruption after the first instillation of epirubicin might have been due to drug toxicity of the agent. However, drug eruptions after the second instillation of epirubicin and the first instillation of mitomycin C might have been due to allergic reactions to the drugs. The patient has not received any further intravesical chemotherapy and has not demonstrated any such a drug eruption again.