Clinical Reasoning: An 82-Year-Old Woman With Subacute Ophthalmoparesis and Ataxia.

We present the case of an 82-year-old woman with subacute altered mental status, oculomotor disturbances, and ataxia. On examination, she exhibited bilateral ptosis, complete horizontal ophthalmoplegia, and limited vertical eye movements during upgaze associated with prominent truncal ataxia. Cerebral MRI showed a mild hyperintensity on T2 and fluid-attenuated inversion recovery sequences in the posterior brainstem extending to the upper cervical cord, without gadolinium enhancement. Clinical and radiologic features suggested an encephalomyelitis with prominent brainstem involvement. We summarize the comprehensive differential diagnosis in patients with subacute brainstem encephalitis, which includes infectious paraneoplastic syndromes and inflammatory disorders. This case highlights the relevance of performing a wide methodical screening for malignancy in case of negative initial workup.

Krebs von den Lungen-6 glycoprotein circulating levels are not useful as prognostic marker in COVID-19 pneumonia: A large prospective cohort study.

Coronavirus disease 2019 (COVID-19) has rapidly expanded worldwide. Currently, there are no biomarkers to predict respiratory worsening in patients with mild to moderate COVID-19 pneumonia. Small studies explored the use of Krebs von de Lungen-6 circulating serum levels (sKL-6) as a prognostic biomarker of the worsening of COVID-19 pneumonia. We aimed at a large study to determine the prognostic value of sKL-6 in predicting evolving trends in COVID-19. We prospectively analyzed the characteristics of 836 patients with COVID-19 with mild lung disease on admission. sKL-6 was obtained in all patients at least at baseline and compared among patients with or without respiratory worsening. The receiver operating characteristic curve was used to find the optimal cutoff level. A total of 159 (19%) patients developed respiratory worsening during hospitalization. Baseline sKL-6 levels were not higher in patients who had respiratory worsening (median {IQR} 315.5 {209-469} vs. 306 {214-423} U/ml p = 0.38). The last sKL-6 and the change between baseline and last sKL-6 were higher in the respiratory worsening group (p = 0.02 and p < 0.0001, respectively). The best sKL-6 cutoff point for respiratory worsening was 497 U/ml (area under the curve 0.52; 23% sensitivity and 85% specificity). sKL-6 was not found to be an independent predictor of respiratory worsening. A conditional inference tree (CTREE) was not useful to discriminate patients at risk of worsening. We found that sKL-6 had a low sensibility to predict respiratory worsening in patients with mild-moderate COVID-19 pneumonia and may not be of use to assess the risk of present respiratory worsening in inpatients with COVID-19 pneumonia.

Anti-Cortactin Autoantibodies Are Associated With Key Clinical Features in Adult Myositis But Are Rarely Present in Juvenile Myositis.

OBJECTIVE: To define the prevalence and clinical phenotype of anti-cortactin autoantibodies in adult and juvenile myositis. METHODS: In this longitudinal cohort study, anti-cortactin autoantibody titers were assessed by enzyme-linked immunosorbent assay in 670 adult myositis patients and 343 juvenile myositis patients as well as in 202 adult healthy controls and 90 juvenile healthy controls. The prevalence of anti-cortactin autoantibodies was compared among groups. Clinical features of patients with and those without anti-cortactin autoantibodies were also compared. RESULTS: Anti-cortactin autoantibodies were more common in adult dermatomyositis (DM) patients (15%; P = 0.005), particularly those with coexisting anti-Mi-2 autoantibodies (24%; P = 0.03) or anti-NXP-2 autoantibodies (23%; P = 0.04). In adult myositis, anti-cortactin was associated with DM skin involvement (62% of patients with anti-cortactin versus 38% of patients without anti-cortactin; P = 0.03), dysphagia (36% versus 17%; P = 0.02) and coexisting anti-Ro 52 autoantibodies (47% versus 26%; P = 0.001) or anti-NT5c1a autoantibodies (59% versus 33%; P = 0.001). Moreover, the titers of anti-cortactin antibodies were higher in patients with interstitial lung disease (0.15 versus 0.12 arbitrary units; P = 0.03). The prevalence of anti-cortactin autoantibodies was not different in juvenile myositis patients (2%) or in any juvenile myositis subgroup compared to juvenile healthy controls (4%). Nonetheless, juvenile myositis patients with these autoantibodies had a higher prevalence of "mechanic's hands" (25% versus 7%; P = 0.03), a higher number of hospitalizations (2.9 versus 1.3; P = 0.04), and lower peak creatine kinase values (368 versus 818 IU/liter; P = 0.02) than those without anti-cortactin. CONCLUSION: The prevalence of anti-cortactin autoantibodies is increased in adult DM patients with coexisting anti-Mi-2 or anti-NXP-2 autoantibodies. In adults, anti-cortactin autoantibodies are associated with dysphagia and interstitial lung disease.

The indirect immunofluorescence assay autoantibody profiles of myositis patients without known myositis-specific autoantibodies.

OBJECTIVES: The indirect immunofluorescence assay (IIFA) is used to screen for the presence of autoantibodies. Our objective was to determine the prevalence and clinical features of IIFA positive myositis patients without known myositis-specific autoantibodies (MSA). METHODS: Sera from healthy comparators (HC) and patients with dermatomyositis (DM), inclusion body myositis (IBM), and polymyositis (PM) with no detectable MSA were tested by IIFA on HEp-2 cells. The pattern of positivity was classified according to the International Consensus on Antinuclear Antibody Patterns. The prevalence and frequency of each IIFA pattern were compared between the different groups. RESULTS: Sera from 100 HC, 71 DM, 53 IBM, and 69 PM subjects were included in the study. The IIFA was positive in 35% HC compared to 66% DM (p<0.001), 49% IBM, and 64% (p<0.001) PM sera. Among IIFA positive sera, the staining was moderate or intense in 43% HC compared to 79% DM (p<0.001) but just 54% IBM, and 52% PM sera. IIFA positivity was predominantly nuclear in all groups (all >69%). The most common pattern in myositis patients was fine speckled with no differences between groups. In general, IIFA positive and negative DM patients showed similar clinical features and disease activity. CONCLUSIONS: Half of MSA-negative DM patients have moderate/strong IIFA positivity, predominantly with a fine speckled pattern. In contrast, MSA-negative PM, IBM, and healthy comparators are more often weakly positive for IIFA. These findings suggest that unidentified autoantibodies are more likely to exist in DM patients than in the other myositis groups.

Anti-HMGCR Specificity of HALIP: A Confirmatory Study.

A distinctive new indirect immunofluorescence pattern in liver tissue has been associated with anti-HMGCR autoantibodies. It is known as HALIP (HMGCR Associated Liver Immunofluorescence Pattern). In this study, we furthered the original studies to demonstrate the association of anti-HMGCR antibodies with the HALIP. Human anti-HMGCR antibodies from patients' sera were purified and incubated with rat triple tissue (kidney/stomach/liver). A characteristic HALIP was observed. Additionally, a colocalization assay of human anti-HMGCR antibodies with rabbit polyclonal anti-HMGCR antibodies showed colocalization of both immunofluorescence patterns. This study confirms that the HALIP is due to human anti-HMGCR antibodies.

Anti-TIF-1γ Antibody Detection Using a Commercial Kit vs In-House Immunoblot: Usefulness in Clinical Practice.

Objectives: Anti-TIF-1γ autoantibody detection is important for cancer screening in patients with dermatomyositis. The gold standard for anti-TIF-1γ detection, immunoprecipitation, is only available from a few specialized laboratories worldwide, so commercial ELISA/immunoblot tests have emerged in recent years. To analyze their usefulness in diagnosing cancer-associated dermatomyositis, we compared Euroimmun Euroline profile with our previously validated in-house immunoblot assay with human recombinant TIF-1γ. Methods: We included 308 adult patients from Hospital de la Santa Creu I Sant Pau and Vall Hebrón Hospital (Barcelona, Spain) tested for anti-TIF-1γ autoantibodies using the Euroline profile and an in-house immunoblot assay. Results: A total of 27 anti-TIF-1γ were detected by the Euroline and 12 by the in-house assay. Fair agreement was observed between Euroline and the in-house immunoblot Cohen's kappa 0.3163. Expected prevalence of anti-TIF-1γ autoantibodies was observed for the two methods for dermatomyositis and undifferentiated connective tissue diseases, but unexpectedly high prevalence of anti-TIF-1γ autoantibodies was detected by Euroline compared to the in-house immunoblot for other diseases (16.5% Euroline vs 0.8% in-house immunoblot, p<0.01). The in-house IB compared to Euroline more reliably detected cancer in patients with DM with anti-TIF-1γ antibodies (p=0.0014 vs p=0.0502 for in-house immunoblot vs Euroline). Conclusion: We recommend using a second validated method to confirm Euroline-detected anti-TIF-1γ antibodies when the dermatomyositis diagnosis is not definitive. Furthermore, in the context of definite DM diagnosis with negative anti-TIF-1γ antibodies by Euroline and no other myositis specific antibody, is also recommendable to confirm by a second validated method.