Association of Dermatomyositis Sine Dermatitis With Anti-Nuclear Matrix Protein 2 Autoantibodies.

Importance: Reports on dermatomyositis (DM) sine dermatitis (DMSD) are scarce, and the concept of the disease has not been widely accepted. Objective: To confirm the existence of DMSD, determine its prevalence, and characterize its serologic features. Design, Setting, and Participants: This is a cohort study that reviewed clinical information, laboratory data, and muscle pathology slides from January 2009 to August 2019. We further assessed the follow-up data of 14 patients with DMSD. The median (interquartile range) follow-up period was 34 (16-64) months. Muscle biopsy samples, along with clinical information and laboratory data, were sent to a referral center for muscle diseases in Japan for diagnosis. Of patients whose myopathologic diagnosis was made at the National Center of Neurology and Psychiatry between January 2009 and August 2019, 199 patients were eligible for inclusion. These patients underwent full investigation for DM-specific autoantibodies (against transcriptional intermediary factor γ, Mi-2, melanoma differentiation-associated gene 5, nuclear matrix protein 2 [NXP-2], and small ubiquitin-like modifier activating enzyme ); however, 17 patients were excluded because their muscle fibers did not express myxovirus resistance protein A, a sensitive and specific marker of DM muscle pathology. Main Outcomes and Measures: Diagnosis of DMSD was based on the absence of a skin rash at the time of muscle biopsy. Results: Of the 182 patients, 93 were women (51%) and 46 were children (25%) (<18 years). Fourteen patients (8%) had DMSD and none were clinically diagnosed with DM. Among the 14 patients with DMSD, 12 (86%) were positive for anti-NXP-2 autoantibodies, while the remaining 2 were positive for anti-transcriptional intermediary factor γ and anti-Mi-2 autoantibodies, respectively. Only 28% of patients (47 of 168) with a skin rash were positive for anti-NXP-2 autoantibodies, indicating a significant association between anti-NXP-2 autoantibodies and DMSD (86% [12 of 14] vs 28% [47 of 168]; P < .001). This association was also supported by multivariable models adjusted for disease duration (odds ratio, 126.47; 95% CI, 11.42-1400.64; P < .001). Conclusions and Relevance: Dermatomyositis sine dermatitis does exist and accounts for 8% of patients with DM confirmed with muscle biopsy. Dermatomyositis sine dermatitis is significantly associated with anti-NXP-2 autoantibodies, which contrasts with anti-MDA5 DM, which is typically clinically amyopathic in presentation. It is essential to distinguish DMSD from other types of myositis because DM-specific therapies that are currently under development, including Janus kinase inhibitors, may be effective for DMSD.

[Ischemic stroke in a young woman of Turner syndrome with T1-weighted imaging-pulvinar sign].

A 39-year-old woman developed right hemiparesis in a few days. Magnetic resonance images revealed cerebral infarction in the territory of the left lenticulostriate artery, and MR angiography showed severe stenosis of the middle and anterior cerebral arteries and moderate one of the vertebral arteries. Bilateral and symmetric T1 hyperintensity in the pulvinar (T1-weighted imaging-pulvinar sign; "T1 pulvinar sign") was detected, which is recognized as a key imaging of Fabry disease. The α-galactosidase A gene analysis, however, showed no mutation. Although specific physical symptoms were solely short stature and oligomenorrhea, the diagnosis of Turner syndrome was confirmed by the chromosome analysis which showed mosaicism of 45XO and 46X,r(X) (60%:40%). To our knowledge, this is the first report of Turner syndrome with "T1 pulvinar sign".

Intracranial invasive aspergillosis originating in the sphenoid sinus: a successful treatment with high-dose itraconazole in three cases.

We report three cases of intracranial aspergillosis originating in the sphenoid sinus in immunocompetent patients. The patients presented with an orbital apex syndrome in that a unilateral loss of vision and cranial nerve III palsy were seen in all cases and a contralateral involvement was also seen in one case. Despite the initial treatment with a conventional dose of itraconazole (ITCZ, 200 mg/day), the neurological deficits failed to improve and the granulomatous inflammation was not suppressed. Therefore, we treated with a combination of a high dose of ITCZ at 500-1000 mg/day (16-24 mg/kg/day) and amphotericin B (AMPH-B) at 0.5 mg/kg/day, in conjunction with a pulse dose of methylprednisolone at 1000 mg/day. Two cases responded favorably in that the ocular movements completely recovered, and their maximum serum concentrations of the hydroxy ITCZ were 7816 ng/ml and 5370 ng/ml. However, the other case worsened, despite ITCZ treatment at 16 mg/kg/day, and the serum concentration of the hydroxy ITCZ was 3863 ng/ml. The surgical decompression of the cavernous sinus via an extradural approach was performed, and the dose of ITCZ was increased to 24 mg/kg/day. The resulting serum concentration of the hydroxy ITCZ was 4753 ng/ml, and the outcome of this case has been favorable. These results suggest that a high blood level of the hydroxy ITCZ (more than 4500 ng/ml) is a prerequisite for the successful treatment of intracranial aspergillosis and that the combination treatment of ITCZ with AMPH-B would be preferred. The concomitant use of steroid and/or surgical decompression should be considered, if the invasiveness is not well-controlled in spite of intensive medical therapy.

[A case of childhood multiple sclerosis presented with meningitis and multiple silent plaques].

A 13-year-old girl presented herself with right optic neuritis and pleocytosis in the cerebrospinal fluid (CSF) in May 2000. Although her vision gradually improved after steroid therapy, the right optic neuritis relapsed a month later, and MRIs of the brain showed multiple high-signal intensity areas in the white matter of the right frontal and parietal lobes on T2-weighted and FLAIR images. She developed nuchal pain, low-grade fever, and general malaise in January 2002. Mononuclear pleocytosis and an elevation of myelin basic protein level were noted in CSF (33/microliter, 17.7 ng/ml, respectively). In addition to the plaque-like lesions seen in June 2000, MRI at this time showed an increase in the number of plaques in the medulla, pons, bilateral cerebellar peduncles and cerebellum. We thus considered this case as MS presenting with no focal neurological deficits but meningitis and asymptomatic MRI lesions. The past history of relapsed optic neuritis is supportive and compatible with that diagnosis. One might assume that the case belongs to that of relapsed type acute disseminated encephalomyelitis (ADEM). However, the cardinal pictures of the case are those of relapsing optic neuritis and multiple asymptomatic plaques despite clinical remission. Some atypical features like meningitis may predominate in clinical presentations of child MS, since immune response in child may differ from that of adult.

[Dramatic but temporary improvements in a case of CNS intravascular malignant lymphomatosis].

A 54-year-old man with a past history of gastric malignant lymphoma treated by the total gastrectomy and the chemotherapy, developed bilateral sudden deafness one year later. Two years after the gastrectomy he became abruptly paraplegic with sensory impairments of the lower extremities and neurogenic bladder. Serum LDH and soluble IL-2 receptor were high in titers (552 U/l and 1,090 U/l, normal range 145-519). Although the imaging studies of the spinal cord were negative, the myelopathic symptoms resolved dramatically after a course of pulse dose methylprednisolone therapy. However, he soon developed an abnormal behavior and mental deterioration in 3 weeks. The MRIs of the brain revealed abnormal signals compatible with multiple cerebral infarctions. As intravascular malignant lymphomatosis (IML) was suspected because of the laboratory and MRI findings, biopsies of the skin, the bone marrow, the muscle and the lymph node were carried out, without evidence of lymphoma. The brain biopsy ultimately confirmed the presence of IML. The patient remarkably responded to biweekly CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) therapy in terms of regaining the mental alertness and improved hearing. However, the CHOP therapy was prematurely interrupted prior to completion because of infective arthritis. The relapse soon ensued, and he died 6 months after admission. This case was of interest because a solid gastric lymphoma appears to have transformed into the form of intravascular lymphomatosis without mass formations or leukemic changes. Although the neurological symptoms in association with IML are thought to be the results of ischemic events, this case illustrates a remarkable reversibility of the symptoms. This implies that the cerebral symptoms are not necessarily the results of typical ischemic infarction, but due to relative ischemia because of chiefly capillary-venous occlusion by lymphoma cells. The majority of the symptoms is thus attributable to the functional impairment. Therefore, the therapeutic intervention may dramatically improve the symptoms due to IML.

[A case of recurrent bacterial meningitis by delayed cerebrospinal fluid (CSF) leakage due to a head trauma].

A 42-year-old man was admitted due to recurrent bacterial meningitis, as he had been treated here for bacterial meningitis three years prior to the current event. He had a remote history of head injury that he had almost forgotten, and his laboratory data showed no immunodeficiency state. 111In-DTPA cisternography showed an abnormal radioactive accumulation in the frontal lobe adjacent to the left frontal sinus at 23 hours after intrathecal injection, and MPR CT images revealed the left frontal sinus bone fracture. These findings indicated that he had a head injury by which a delayed CSF fistula has been formed. He was surgically treated for a CSF leakage. Although a combination therapy of ABPC and CTRX was efficacious for this patient, this regimen may not be ideal, as meningitis by PRSP has been increasing in incidence. Pneumococcal meningitis, once not a difficult infection to treat, could be a difficult one, as resistant strains to ABPC and CTRX have been more common.