Pharmacologic Treatment of Anti-MDA5 Rapidly Progressive Interstitial Lung Disease.

Purpose of the Review: Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders. The presence of different autoantibodies allows clinicians to define distinct phenotypes. Antibodies against the melanoma differentiation-associated protein 5 gene, also called anti-MDA5 antibodies, are associated with a characteristic phenotype, the clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease. This review aims to analyze the different pharmacological options for the treatment of rapidly progressive interstitial lung disease in patients with anti-MDA5 antibodies. Recent Findings: Evidence-based therapeutic recommendations suggest that the best initial approach to treat these patients is an early combination of immunosuppressive drugs including either glucocorticoids and calcineurin inhibitors or a triple therapy adding intravenous cyclophosphamide. Tofacitinib, a Janus kinase inhibitor, could be useful according to recent reports. High ferritin plasma levels, generalized worsening of pulmonary infiltrates, and ground-glass opacities should be considered predictive factors of a bad outcome. In this scenario, clinicians should consider rescue therapies such as therapeutic plasma exchange, polymyxin-B hemoperfusion, veno-venous extracorporeal membrane oxygenation, or even lung transplantation. Summary: Combined immunosuppressive treatment should be considered the first-line therapy for patients with anti-MDA5 rapidly progressive interstitial lung disease. Aggressive rescue therapies may be useful in refractory patients.

Recommendations for the treatment of anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated rapidly progressive interstitial lung disease.

OBJECTIVES: The study aimed to develop evidence-based recommendations for the treatment of rapidly progressive interstitial lung disease (RPILD) associated with the anti-Melanoma Differentiation-Associated Gene 5-positive dermatomyositis (DM) syndrome. METHODS: The task force comprised an expert panel of specialists in rheumatology, intensive care medicine, pulmonology, immunology, and internal medicine. The study was carried out in two phases: identifying key areas in the management of DM-RPILD syndrome and developing a set of recommendations based on a review of the available scientific evidence. Four specific questions focused on different treatment options were identified. Relevant publications in English, Spanish or French up to April 2018 were searched systematically for each topic using PubMed (MEDLINE), EMBASE, and Cochrane Library (Wiley Online). The experts used evidence obtained from these studies to develop recommendations. RESULTS: A total of 134 studies met eligibility criteria and formed the evidentiary basis for the recommendations regarding immunosuppressive therapy and complementary treatments. Overall, there was general agreement on the initial use of combined immunosuppressive therapy. Combination of high-dose glucocorticoids and calcineurin antagonists with or without cyclophosphamide is the first choice. In the case of calcineurin antagonist contraindication or treatment failure, switching or adding other immunosuppressants may be individualized. Plasmapheresis, polymyxin B hemoperfusion and/or intravenous immunoglobulins may be used as rescue options. ECMO should be considered in life-threatening situations while waiting for a clinical response or as a bridge to lung transplant. CONCLUSIONS: Thirteen recommendations regarding the treatment of the anti-MDA5 positive DM-RPILD were developed using research-based evidence and expert opinion.

Prevalence of HHV-8 in systemic autoimmune diseases.

BACKGROUND: Epidemiological data suggest that some viruses may be linked to the development of autoimmunity. OBJECTIVES: The objective of this work was to determine the presence of HHV-8 viral DNA in whole blood from patients suffering from different systemic autoimmune diseases (SAD). We also aimed at testing the prevalence of patients showing antibodies against an HHV-8 orfK8.1 peptide. STUDY DESIGN: Two hundred and eighty SAD patients and 50 healthy blood donor controls were included. Molecular analyses were performed by nested PCR from DNA obtained from whole blood and an enzyme immunoassay was developed in order to test for the presence of antibodies directed against a synthetic peptide derived from the HHV-8 orfK8.1 protein. RESULTS: Only 2 out of the 280 samples analyzed yielded the specific HHV-8 PCR product. Antibodies against orfK8.1 were detected in 2 SLE patients, 1 patient suffering from Sjögren's syndrome and 2 patients with vasculitis. CONCLUSIONS: We conclude that HHV-8 is usually not present in blood neither from autoimmune patients nor from healthy controls. Furthermore, HHV-8 antibodies against the HHV-8 orfK8.1 peptide were rarely detected. It leads us to infer that HHV-8 is not involved on the development of these disorders. It does not rule out the possibility that other environmental and microbiological triggers may account for their etiopathogenesis.

The diagnosis and classification of polymyositis.

Polymyositis is classified as a separate entity among idiopathic inflammatory myopathies but it is considered as the least common since it is an exclusion diagnosis. This myopathy usually presents with subacute-chronic symmetric proximal limb weakness, although some extramuscular manifestations are common. Creatine kinase values may be increased up to 50-fold in active disease. Muscle biopsy is characterized by endomysial inflammatory infiltrate consisting predominantly of CD8+ T cells that invade healthy muscle fibres expressing the MHC-I antigen. Although serum autoantibodies, EMG and imaging techniques can help in diagnosis, muscle histopathology is a pivotal value. The clinical picture together with the pathological findings confers the also called PM pattern. A broad differential diagnosis is needed before concluding a diagnosis of pure PM. Sporadic inclusion-body myositis, toxic, endocrine and metabolic myopathies as well as muscular dystrophies are the major categories to be ruled out. Finally, a diagnostic algorithm for suspected cases of PM is also proposed.

Eosinophilic myositis: an updated review.

Eosinophilia-associated myopathies are clinically and pathologically heterogeneous conditions characterized by the presence of peripheral and/or muscle eosinophilia. There are at least three distinct subtypes: focal eosinophilic myositis, eosinophilic polymyositis, and eosinophilic perimyositis. Infiltrating eosinophils are not always identified in conventional muscle histologic examination, but the eosinophil major basic protein, whose extracellular diffusion is considered a hallmark of eosinophilic cytotoxicity, is usually detected by immunostaining in muscle biopsy. Whereas focal eosinophilic myositis seems to be a benign and isolated condition, and perimyositis is usually related with the inflammatory infiltrate due to fasciitis, eosinophilic polymyositis can be associated with muscular dystrophy or be a feature of multiorgan hypereosinophilic syndrome. Muscle biopsy remains the cornerstone for the diagnosis. Parasitic infections, connective tissue disorders, hematologic and non-hematologic malignancies, drugs, and toxic substances are the main etiologic agents of eosinophilia-associated myopathy. However, in some cases, no known etiologic factor is identified, and these are considered idiopathic. Glucocorticoids are the mainstay therapy in idiopathic forms. Imatinib and mepolizumab, a humanized anti-interleukin 5 monoclonal antibody, may be useful in patients with eosinophilic myositis as part of a hypereosinophilic syndrome.

Diagnosis and classification of eosinophilic fasciitis.

Eosinophilic fasciitis (EF) is a rare scleroderma-like syndrome with an unknown etiology and pathogenesis that should be considered an immune-allergic disorder. Painful swelling with progressive induration and thickening of the skin and soft tissues of the limbs and trunk are the clinical hallmarks of the disease. Peripheral blood eosinophilia, hypergammaglobulinemia, and elevated erythrocyte sedimentation rate are the main laboratory findings. Full-thickness wedge biopsy of the clinically affected skin showing inflammation and thickening of deep fascia is essential to establish the diagnosis. The differential diagnosis includes systemic sclerosis and other scleroderma subsets such as morphea, and epidemic fasciitis syndromes caused by toxic agents such as the myalgia-eosinophilia syndrome and toxic oil syndrome. Peripheral T cell lymphomas should also be ruled out. The diagnosis of EF can be established by clinical, laboratory and histological findings, but universally accepted international diagnostic criteria are lacking. Corticosteroids are efficacious and remain the standard therapy for EF, although some patients may improve spontaneously.

[Primary Sjögren's syndrome: clinical and immunological characteristics of 114 patients]. / Síndrome de Sjögren primario: características clínicas e inmunológicas de 114 pacientes.

BACKGROUND: To analyze the clinical and immunological characteristics of a series of 114 patients with primary Sjögren's syndrome (PSS), and to evaluate the different diagnostic criteria and the association to lymphoproliferative disorders. PATIENTS AND METHOD: We included 114 patients (108 female and 6 male) with a diagnosis of PSS. All patients fulfilled the 1993 European Community criteria for the diagnosis of PSS and 76 patients fulfilled the San Diego Criteria. RESULTS: Mean age was 51 years with a mean follow-up of 7.3 years. The commonest clinical manifestation at onset (70%) was xerostomia/xerophtalmia (sicca syndrome). Extra glandular involvement was articular in 42% of cases, neurologic (35%), respiratory (21%) and hepatic (13%). Eleven patients (9%) developed vasculitis, and three (2%) developed a lympho-proliferative disorder. No statistically significant differences regarding symptoms at onset, frequency of glandular or extra glandular manifestations and severity of disease were observed between the two diagnostic criteria groups. HCV infection was associated with vasculitis (p < 0.001; OR: 20.6; CI 95%, 3.2-129) and lymphoproliferative disorders (p < 0.001). CONCLUSIONS: The clinical evolution of PSS does not vary when using different diagnostic criteria (San Diego and European Community criteria). A subset of patients with vasculitis and lymphoproliferative diseases is found to have an associated HCV infection.

[Comorbidity, hospitalization, and drug use for non-exacerbated chronic disease in the elderly population]. / Comorbilidad, ingreso hospitalario y consumo de fármacos por enfermedad crónica no reagudizada en población anciana.

OBJECTIVES: To evaluate the prevalence of comorbidity among elderly hospitalized patients and its influence on discharge diagnosis and medication due to non-exacerbated chronic disease (NECD). To evaluate the impact of hospital admission on the use of drugs due to NECD since admission to the month of discharge. METHODS: A study was made of 85 patients aged 65 years or older collected during two consecutive months. The study protocol consisted of a questionnaire on comorbidity, study of drug consume, discharge diagnosis and follow-up for one month post discharge. RESULTS: Patients had a mean of 6.4 chronic diseases; significant differences were observed regarding discharge report (mean: 2.1). The number of drugs due to NECD prior to admission (mean: 2.9), at discharge (1.5) and one month after discharge (1.9) showed significant differences between those prior to admission, at discharge, and one month after discharge (p < 0.0001). Hospital admission involved a decrease (p < 0.0001) in the number of patients with polypharmacy criteria (more than four drugs), which persisted one month after discharge (p < 0.01), and in the prescription of polyvitaminic compounds, nonsteroid antiinflammatory drugs, antiaggregants, peripheral vasodilators and antacids (p < 0.03). CONCLUSIONS: A relevant under-reporting of chronic diseases in the discharge report, particularly of those without exacerbations, as well as quantitative (decrease) and qualitative changes in the prescription due to NECD, maintained by the general practitioner one month after discharge. A higher awareness regarding chronic disease is necessary, as well as chronic disease is necessary, as well as establishing communication channels between Primary and Specialized Care.

Raynaud's phenomenon and positive antinuclear antibodies in a malignancy.

Both Raynaud's phenomenon and the presence of antinuclear antibodies are uncommon features of malignant disease and the association of both with a malignancy extremely rare. The case is reported of a 78 year old woman who presented with Raynaud's phenomenon and positive antinuclear antibodies related to adenocarcinoma of unknown primary site.