[A CASE OF CLINICALLY AMYOPATHIC DERMAMYOSITIS WITH INTERSTITIAL LUNG DISEASE SHOWING TWO DETERIORATIONS IN 4 YEARS].

We report the case of a 45-year-old man who was diagnosed with clinically amyopathic dermamyositis (CADM) and interstitial lung disease (ILD) after presenting with skin lesions typical of CADM and testing positive for anti-Melanoma Diferentiation-Associated gene 5 (anti-MDA5) anti-bodies. He was treated with a regimen including steroid pulse therapy, intravenous cyclophosphamide (IVCY), and calcineurin Inhibitor drug, which initially improved his ILD. However, three months post-treatment, the first deterioration of his conditions occurred, necessitating further administration of steroid pulse therapy and IVCY. After eight cycles of IVCY therapy, the serum levels of KL-6 and anti-MDA5 antibodies decreased, and reaching their lowest values. Nevertheless, two years and six months after the first observed deterioration, the second deterioration of his conditions occurred, leading to acute respiratory failure, treated again with steroid pulse therapy and IVCY. This treatment did not result in improvement of respiratory failure, therefore plasma exchange was attempted, which demonstrated a beneficial effect on the ILD for a short time. This case suggests that IVCY and plasma exchange might be effective therapeutic options for CADM with ILD.

Oral mucous membrane pemphigoid: updates in diagnosis and management.

Mucous membrane pemphigoid (MMP) is a rare, immune-mediated, vesiculobullous disease that predominantly affects the oral cavity and conjunctiva. In MMP, autoantibodies are directed against hemidesmosomal proteins in the basement membrane zone, most commonly BP180. Clinical signs and symptoms include gingival desquamation, erosions, and ulcerations. Differential diagnoses include other immune-mediated blistering diseases, such as bullous pemphigoid. Definitive diagnosis is reached through history taking, physical examination, tissue biopsy and/or serology testing. MMP, although not curable, is typically managed with topical or systemic corticosteroids, in addition to immunosuppressive therapies and biologic agents in recalcitrant cases. Untreated MMP can lead to life-threatening complications, such as blindness. As a condition that affects the oral cavity, it is important that dentists understand how to recognise, diagnose and manage the disease.

Prevalence and Associated Factors for Thyroid Dysfunction Among Patients On Targeted Therapy for Cancers: A Single-Center Study from Thailand.

Objective: This study aimed to explore the prevalence and associated factors of thyroid dysfunction among cancer patients treated with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). Methodology: A cross-sectional study was done in patients who received TKIs at Rajavithi Hospital in 2019. For patients treated with ICI, a retrospective chart review for patients seen in 2018 to 2019 was conducted. If there were abnormal thyroid function tests (TFT), thyroid autoantibodies were tested. Results: There were 144 patients on TKIs with a mean age of 56.0 years. Thyroid dysfunction was found in 14.6% of patients and most had subclinical hypothyroidism (n = 16, 11.1%). Imatinib (n = 11, 10.8%) and sunitinib (n = 4, 100%) were the 2 most common TKIs given to patients with thyroid dysfunction. Thyroid dysfunction was associated with male sex, chronic kidney disease and hepatitis B virus infection but not with previous thyroid disease and presence of thyroid autoantibodies.There were 18 patients who received ICIs. The mean age was 63.3 years. Twelve patients (66.7%) used programmed cell death protein-1 antibody (anti-PD1), mainly nivolumab. Thyroid dysfunction was found in 50%, which occurred at a median duration of 46 days. Most patients had overt hypothyroidism and 55.6% needed levothyroxine replacement. Conclusion: Thyroid dysfunctions from TKIs were mostly asymptomatic and mild in severity. Some types of TKIs might be associated with thyroid dysfunction. On the other hand, thyroid dysfunction from ICIs usually occurs within 6 months and requires levothyroxine replacement.

The selective inhibition of the Syk tyrosine kinase ameliorates experimental autoimmune arthritis.

Autoimmune arthritis - such as rheumatoid arthritis - affect a significant proportion of the population, which can cause everyday joint pain, decreased mobility and reduced quality of life. Despite having more and more therapeutic options available, there are still a lot of patients who cannot reach remission or low disease activity by current therapies. This causes an urgent need for the development of new treatment options. The Syk tyrosine kinase plays an essential role in B cell receptor, Fc receptor and integrin signaling. It has been shown that the hematopoietic cell-specific deletion of Syk resulted in a complete protection against autoantibody-induced experimental arthritis. This prompted us to test the effect of entospletinib, a second generation, Syk-selective inhibitor, which has a tolerable safety profile according to hematological clinical trials, in experimental autoimmune arthritis. We found that entospletinib dose-dependently decreased the macroscopic signs of joint inflammation, while it did not affect the health status of the animals. In line with these findings, local neutrophil accumulation and cytokine levels were reduced compared to the vehicle-treated group, while macrophage accumulation and synovial fibroblast numbers were not significantly altered. Meanwhile, entospletinib dose-dependently decreased the cell responses of immune complex- or integrin ligand-activated neutrophils. Overall, we found that selective Syk inhibition by entospletinib reduced the activity of autoantibody-induced experimental arthritis, which seems to be based mainly on the effect of the inhibitor on neutrophil functions. Our data raise the possibility that entospletinib could be a good drug candidate in the treatment of human autoimmune arthritis.

Clinical features and outcomes of patients with muscle-specific kinase antibody-positive myasthenia gravis in Japan.

This study included 51 patients with muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) from a Japanese multicenter survey to examine clinical features and outcomes. Median onset age was 37 years and female predominance was observed. All patients developed generalized symptoms and almost all (50/51) patients had bulbar symptoms. About half of the patients met the criteria for refractory MG. The refractory group had a lower age of onset, higher severity scores, and higher maximum daily doses of oral prednisolone compared to the nonrefractory group. The outcomes for MuSK-MG patients in Japan are not favorable, indicating the need for more aggressive treatment.

[Report of two cases of anti-LGI1 autoimmune encephalitis in Mexico]. / Reporte de dos casos de encefalitis autoinmune anti-LGI1 en México.

Background: Anti-LGI1 encephalitis is characterized by a pattern of inflammation that predominantly affects the limbic system It is part of the autoimmune encephalitis that attack neuronal surface antigens. It is characterized by the triad of subacute dementia, faciobrachial dystonic crises, and hyponatremia, presenting an excellent response to immunotherapy. The aim of this article is to describe the clinical evolution and functional outcome at 6 months of two patients with anti-LGI1 encephalitis using clinical cases. Clinical cases: Case 1: 62-year-old man with 8-week symptoms manifested by changes in mood, disorientation, and focal motor seizures. Case 2 A 72-year-old woman with a 5-month evolution of rapidly progressive dementia, hyponatremia and bitemporal hyperintensities on MRI. In both, due to clinical suspicion, acute dual immunotherapy with steroid and immunoglobulin was given with substantial improvement. Subsequently, the existence of anti-LGI1 antibodies in cerebrospinal fluid was confirmed. Although both patients received a dose of rituximab during their hospitalization, only the patient in the first case continued biannual doses of rituximab. The second patient was not initially considered to continue long-term immunomodulatory treatment and experienced a relapse. Conclusions: These clinical vignettes present the reader with the classic characteristics of this disease. This can facilitate its recognition and timely initiation of treatment, improving the functional prognosis of patients.

Introducción: la encefalitis anti-LGI1 se caracteriza por un patrón de inflamación que afecta de forma predominante al sistema límbico. Forma parte de las encefalitis autoinmunes que atacan a antígenos de superficie neuronal. Se caracteriza por la tríada de demencia subaguda, crisis distónicas faciobraquiales e hiponatremia, presentando una respuesta excelente a la inmunoterapia. El objetivo de este trabajo es describir por casos clínicos la evolución clínica y resultado funcional a 6 meses de dos pacientes con encefalitis anti-LGI1. Casos clínicos: caso 1: hombre de 62 años con cuadro de 8 semanas, manifestado por cambios en el estado de ánimo, desorientación y crisis focales motoras. Caso 2: mujer de 72 años con una evolución de 5 meses de demencia rápidamente progresiva, hiponatremia e hiperintensidades bitemporales en RMN. En ambos, ante la sospecha clínica, se otorgó inmunoterapia dual aguda con esteroide e inmunoglobulina con mejoría sustancial, posteriormente se corroboró la existencia de anticuerpos anti-LGI1 en líquido cefalorraquídeo. Pese a que ambos pacientes recibieron una dosis de rituximab durante su hospitalización, solo el primer caso continuó dosis semestrales de rituximab. El segundo no fue considerado inicialmente para continuar con tratamiento inmunomodulador a largo plazo y presentó una recaída. Conclusiones: estos casos, presentan al lector las características clásicas de esta enfermedad. Esto puede facilitar su reconocimiento y la instauración oportuna del tratamiento, mejorando el pronóstico funcional de los pacientes.

Atypical form of Goodpasture's disease.

Goodpasture's disease and anti-glomerular basement membrane nephritis (anti-GBM nephritis) are rare autoimmune small vessel vasculitis predominantly affecting young men. Goodpasture's disease plays an important part in differential diagnosis of pulmonary - renal syndrome. The evidence of circulating autoantibodies, a typical histological appearance of the kidney biopsy with finding of the crescent glomerulonephritis and clinical presentation of nephritic syndrome play an important role in diagnosis. Our case report describes a case of a young male with anti-GBM nephritis that presents as rapidly progressive glomerulonephritis (RPGN) with progression to dialysis-dependent renal failure. The atypical sign of the case was development of nephrotic syndrome with volume-dependent hypertension. The case was complicated by heparin-induced thrombocytopenia. During combined immunosuppressive therapy with plasmapheresis, the condition of the patient has stabilized. However, renal function did not recover. This previously fatal disease has nowadays a very good survival rate because of immunosuppresion therapy, plasmapheresis and hemodialysis.

Autoimmune Axonal Neuropathies.

OBJECTIVE: This article reviews autoimmune axonal neuropathies, their characteristic clinical features, disease and antibody associations, appropriate ancillary testing, treatment, and prognosis. LATEST DEVELOPMENTS: In 2021, the American College of Rheumatology and the Vasculitis Foundation released new summary guidelines for the treatment of antineutrophil cytoplasmic autoantibody-associated vasculitides. In addition, novel autoantibodies have been recently identified; they are often paraneoplastic and associated with axonal neuropathies. ESSENTIAL POINTS: Recognition of autoimmune axonal neuropathies is important because of the potential for effective treatment to either reverse deficits or slow the progression of disease. It is necessary to properly assess for associations with other systemic disorders (eg, systemic vasculitis, connective tissue disease, neoplasm) so that adequate treatment for both neurologic and non-neurologic aspects of the disease can be initiated.

[Clinically amyopathic dermatomyositis : a rare entity associated with acute and severe interstitial lung disease]. / La dermatomyosite amyopathique : une entité rare associée à une pneumopathie interstitielle fulminante.

Dermatomyositis is a rare disease of unknown etiology characterized by a severe inflammatory myopathy associated with a cutaneous syndrome. Dermatomyositis is associated with multisystemic disorders mostly represented by cardiac, pulmonary and articular involvements, which are particularly associated with a bad prognosis. We report a case of a 50-year-old patient suffering from dermatomyositis associated with an interstitial lung disease with a particularly fast and pejorative clinical evolution. The anti-Melanoma Differentiation-Associated gene 5 (anti-MDA5) antibodies are frequently associated with a severe and rapidly progressive lung disease without myositis named «amyopathic dermatomyositis¼. High blood levels of anti-MDA5 were found in our patient. Despite maximal immunosuppressive treatment and supportive care, he died 3 months after the diagnosis. Patients may present different antibodies that correspond to distinct clinical phenotypes of dermatomyositis. The anti-MDA5 is known to be a marker of clinically amyopathic dermatomyositis (CADM) associated with a rapidly progressive interstitial lung disease. Moreover, blood level of anti-MDA5 antibody predicts the response to treatment and survival in CADM.

La dermatomyosite est une maladie rare, d'étiologie inconnue, caractérisée par une myopathie inflammatoire associée à un syndrome cutané typique. Outre l'atteinte musculaire et cutanée, la dermatomyosite peut se manifester par des atteintes organiques, notamment pulmonaires, cardiaques et articulaires qui contribuent à la sévérité de la maladie. Nous rapportons le cas d'un patient âgé de 50 ans atteint d'une dermatomyosite compliquée d'une pneumopathie interstitielle d'évolution clinique particulièrement rapide et péjorative. Le patient présentait des anticorps anti-MDA5 (anti-Melanoma Differentiation-Associated gene 5), anticorps associés assez fréquemment à une atteinte pulmonaire sévère et rapidement progressive, ainsi qu'à une présentation particulière de la maladie appelée «dermatomyosite amyopathique¼. Malgré un traitement immunosuppresseur intensif, l'état pulmonaire du patient s'est rapidement aggravé, entraînant son décès par insuffisance respiratoire trois mois après le diagnostic. Cette histoire clinique illustre le fait que les patients atteints de dermatomyosite peuvent présenter différents anticorps qui correspondent à des phénotypes cliniques distincts. L'association entre anticorps anti-MDA5 et la pathologie pulmonaire interstitielle justifie qu'un screening des anticorps anti-MDA5 soit réalisé chez les patients porteurs d'une dermatomyosite. De plus, le titrage sanguin des anti-MDA5 est un facteur pronostique de la réponse au traitement et de la survie.

Histology and clinical correlations in autoimmune hepatitis, primary biliary cholangitis, and autoimmune hepatitis-primary biliary cholangitis overlap syndrome.

OBJECTIVES: The diagnosis of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and AIH-PBC overlap syndrome (OS) relies on their histologic features and clinical findings. In this study, we aimed to identify specific morphologic features of these diseases and evaluate their clinical correlation. METHODS: We included initial biopsies from untreated patients with AIH (n = 14), PBC (n = 10), and OS (n = 7). Histologic features of the portal tract, portal-lobular interface, and hepatic lobule, fibrosis, as well as clinical data including serology, autoantibodies, treatment, and prognosis were reviewed and analyzed. RESULTS: Our results showed that several histologic features differed significantly between AIH and PBC (p < 0.05). Among these features, OS cases were more likely to present with bile duct-centered processes (presence of bile duct damage while absence of inflammation gradient from bile duct to interface, plasma cell cluster and pericentral inflammation) unlike those seen in AIH (p < 0.05), and interface-centered processes (unequivocal interface hepatitis, ductular reaction, and periportal fibrosis) which were not seen in PBC (p < 0.05). We observed a significant correlation between transaminase levels and lobular inflammation, including numbers of lymphocyte, plasma cell and eosinophil. Our study also found that anti-smooth muscle antibody positivity was associated with interface hepatitis (p < 0.01), while antimitochondrial antibody positivity was associated with duct damage (including ductopenia) and granulomas (p < 0.05). CONCLUSION: Our results highlight distinctive morphological features between AIH and PBC. The possibility of overlap syndrome should be considered when encountering AIH with bile duct-centered processes or PBC with interface-centered processes in morphology and correlation with autoantibodies.

Preexisting autoantibodies as predictor of immune related adverse events (irAEs) for advanced solid tumors treated with immune checkpoint inhibitors (ICIs).

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are now standard of care in many cancers. They can generate immune-related adverse events (irAEs), but no biomarkers are available to identify patients who are more likely to develop irAEs. We assess the association between pre-existing autoantibodies and occurrence of irAEs. PATIENTS AND METHODS: We prospectively collected data from consecutive patients receiving ICIs for advanced cancers, in a single center between May 2015 and July 2021. Autoantibodies testing was performed before ICIs initiation including AntiNeutrophil Cytoplasmic Antibodies, Antinuclear Antibodies, Rheumatoid Factor anti-Thyroid Peroxidase and anti-Thyroglobulin. We analyzed the associations of pre-existing autoantibodies with onset, severity, time to irAEs and with survival outcomes. RESULTS: Of the 221 patients included, most had renal cell carcinoma (n = 99; 45%) or lung carcinoma (n = 90; 41%). Grade ≥2 irAEs were more frequent among patients with pre-existing autoantibodies: 64 (50%) vs. 20 (22%) patients (Odds-Ratio= 3.5 [95% CI=1.8-6.8]; p < 0.001) in the positive vs negative group, respectively. irAEs occurred earlier in the positive group with a median time interval between ICI initiation and irAE of 13 weeks (IQR = 8.8-21.6) vs. 28.5 weeks (IQR=10.6-55.1) in the negative group (p = 0.01). Twelve patients (9.4%) experienced multiple (≥2) irAEs in the positive group vs. 2 (2%) in the negative group (OR = 4.5 [95% CI: 0.98-36], p = 0.04). After a median follow-up of 25 months, median PFS and OS were significantly longer among patients experiencing irAE (p = 0.00034 and p = 0.016, respectively). CONCLUSION: The presence of pre-existing autoantibodies is significantly associated with the occurrence of grade ≥2 irAEs, with earlier and multiple irAEs in patients treated with ICIs.

Dermatomyositis: a comprehensive review of clinical manifestations, serological features, and therapeutic approaches.

Dermatomyositis (DM) is an autoimmune disorder, which belongs to a group of rare autoimmune dermatoses characterized by different skin features and variable muscle involvement. We recognize four main variants of DM: classic DM, clinically amyopathic DM, paraneoplastic DM, and juvenile DM. Clinically, patients show several skin features, but heliotrope rash, and violaceous papules located at the interphalangeal or metacarpophalangeal joints (Gottron's papules) are the most frequently observed. Together with skin features, patients show muscle involvement, most commonly with symmetrical weakness of the proximal muscles. DM belongs to the facultative paraneoplastic dermatoses and a wide range of solid or hematologic malignancies can be detected in DM patients. Serologically, a wide range of autoantibodies can be detected in patients with DM. Indeed, distinct serotypes can be related to specific phenotypes with specific clinical features, carrying a different risk for systemic involvement and for malignancies. Systemic corticosteroids are still considered the first-line approach, but several steroid-sparing agents, such as methotrexate, azathioprine or mycophenolate mofetil, have been reported as effective in treating DM. Furthermore, new class of drugs, such as monoclonal antibodies, purified immunoglobulins or Janus kinase inhibitors are becoming more relevant in the clinical practice or are currently under investigation. In this work, we aim to offer a clinical overview of the diagnostic workout, the characteristics of DM variants, the role of autoantibodies in DM, and the management of this life-threatening systemic disorder.

Predictive value of CXCL10 for the occurrence of immune-related adverse events in patient with renal cell carcinoma.

Immune checkpoint inhibitors (ICIs) have recently improved the prognosis of various cancers. By contrast, some immune-related adverse events (irAEs) caused by ICIs are fatal and have become problematic. The pathogenesis of irAEs remains unknown and must be elucidated to establish biomarkers. This study investigated plasma cytokine, chemokine, and anti-CD74 autoantibody levels in patients with renal cell carcinoma (RCC) and analyzed their association with irAEs. In a discovery cohort of 13 patients, plasma levels of chemokine (C-X-C motif) ligand (CXCL) 1, IL-17A, IL-1ß, IL-6, IL-8, CXCL10, MCP-1, and TNFα were measured at baseline and post-dose 1. Only CXCL10, at post-dose 1 but not at baseline, was significantly associated with grade 2 or higher irAEs (P = 0.0413). Plasma CXCL10 levels were then measured at baseline and post-dose 1 in an extended cohort of 43 patients with RCC who received ICI-based treatment. Higher plasma CXCL10 levels both at baseline and post-dose1 were significantly associated with the occurrence of grade 2 or higher irAEs (P = 0.0246 and 0.0137, respectively). Plasma CXCL13 levels, which we measured in a previous study, were significantly higher in patients with grade 2 or higher irAEs at baseline but not at post-dose 1 (P = 0.0037 and 0.052, respectively). No significant association between plasma anti-CD74 autoantibody level and both irAE pneumonitis and any grade 2 or higher irAE was observed. In conclusion, plasma CXCL10 is significantly associated with the occurrence of irAEs in patients with RCC treated with ICIs. CXCL10 is a potential predictive and on-treatment biomarker for irAEs.

A feline model of spontaneously occurring autoimmune limbic encephalitis.

Autoimmune encephalitis (AE) is an important cause of encephalitis in humans and occurs at a similar rate to infectious encephalitis. It is frequently associated with antibodies against the extracellular domain of neuronal proteins. Among human AE, that with antibodies against leucine-rich glioma-inactivated 1 (LGI1) is one of the most prevalent forms, and was recently described in cats with limbic encephalitis (LE). In this study, we describe a large cohort (n = 32) of cats with AE, tested positive for voltage gated potassium channel (VGKC)-antibodies, of which 26 (81%) harboured LGI1-antibodies. We delineate their clinical and paraclinical features as well as long-term outcomes up to 5 years. Similar to human cases, most cats with LGI1-antibodies had a history of focal seizures (83%), clustering in the majority (88%), with interictal behavioural changes (73%). Among feline AE patients, there was no seizure type or other clinical characteristic that could distinguish LGI1-antibody positive from negative cats, unlike the pathognomic faciobrachial dystonic seizures seen in humans. Although six cats were euthanased in the first year for epilepsy-associated reasons, those attaining at least 1-year survival had good seizure control and quality of life with appropriate veterinary care and medication. Acute-phase immunotherapy (prednisolone) was given to the most severely unwell cases and its effect is retrospectively evaluated in 10 cats. Our data show LGI1-antibodies are an important cause of feline encephalitis, sharing many features with human AE. Further research should examine optimal therapeutic management strategies and the cause of LE in seronegative cats, building on paradigms established in the counterpart human disease.

Differentially expressed genes in systemic sclerosis: Towards predictive medicine with new molecular tools for clinicians.

Systemic sclerosis (SSc) is a rare and chronic autoimmune disease characterized by a pathogenic triad of immune dysregulation, vasculopathy, and progressive fibrosis. Clinical tools commonly used to assess patients, including the modified Rodnan skin score, difference between limited or diffuse forms of skin involvement, presence of lung, heart or kidney involvement, or of various autoantibodies, are important prognostic factors, but still fail to reflect the large heterogeneity of the disease. SSc treatment options are diverse, ranging from conventional drugs to autologous hematopoietic stem cell transplantation, and predicting response is challenging. Genome-wide technologies, such as high throughput microarray analyses and RNA sequencing, allow accurate, unbiased, and broad assessment of alterations in expression levels of multiple genes. In recent years, many studies have shown robust changes in the gene expression profiles of SSc patients compared to healthy controls, mainly in skin tissues and peripheral blood cells. The objective analysis of molecular patterns in SSc is a powerful tool that can further classify SSc patients with similar clinical phenotypes and help predict response to therapy. In this review, we describe the journey from the first discovery of differentially expressed genes to the identification of enriched pathways and intrinsic subsets identified in SSc, using machine learning algorithms. Finally, we discuss the use of these new tools to predict the efficacy of various treatments, including stem cell transplantation. We suggest that the use of RNA gene expression-based classifications according to molecular subsets may bring us one step closer to precision medicine in Systemic Sclerosis.

Antitumor Immune Mechanisms of the Anti-Complement Factor H Antibody GT103.

Development of novel therapeutic antibodies that not only kill tumor cells but modulate the adaptive immune response has the potential to produce long term anticancer immunity and a durable clinical response. We previously reported the discovery of anti-complement factor H (CFH) autoantibodies in patients with lung cancer that were associated with early-stage disease and exceptional outcomes. The human mAb GT103, produced from a single CFH autoantibody-expressing B cell of a patient with lung cancer, recognizes a conformationally distinct epitope on tumor cells, kills tumor cells, and inhibits tumor growth in animal studies. Recent experiments have shown that GT103 restructures the tumor microenvironment and initiates a robust antitumoral adaptive immune response. The current study further elucidates several mechanisms by which GT103 kills tumor cells and drives the immune program. Here we show GT103 has specificity for tumor cells without binding to native soluble CFH or normal tissues. GT103 causes complement C3 split product deposition on tumor cells in vitro and in vivo, triggers antibody-dependent cellular phagocytosis, and increases translocation of the danger-associated molecular pattern molecule calreticulin to the plasma membrane. We also demonstrate that GT103 causes B-cell activation in vitro and in vivo, and that GT103 antitumor activity in vivo is B-cell dependent. The complex mechanism of GT103, a tumor-specific antibody that kills tumor cells and stimulates an immune response, supports further development of this human-derived antibody as a novel therapeutic option for patients with lung cancer.

Efgartigimod Alfa in Generalised Myasthenia Gravis: A Profile of Its Use.

Intravenous efgartigimod alfa (also known as efgartigimod alfa-fcab in the USA; Vyvgart®) is the first neonatal Fc receptor antagonist approved in several countries worldwide, including the USA and EU for the treatment of generalised myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) antibody positive, and in Japan for the treatment of gMG regardless of antibody status. In the double-blind, placebo-controlled phase 3 ADAPT trial in patients with gMG, efgartigimod alfa significantly and rapidly reduced disease burden and improved muscle strength and quality of life compared with placebo. The clinical benefits of efgartigimod alfa were durable and reproducible. Furthermore, in an interim analysis of the ongoing open-label phase 3 ADAPT+ extension trial, efgartigimod alfa provided consistent clinically meaningful improvements in patients with gMG. Efgartigimod alfa was generally well tolerated, with most adverse events being mild to moderate in severity.

Generalised myasthenia gravis (gMG) is a chronic, autoimmune neuromuscular disorder that can significantly impair quality of life. Several novel targeted therapeutic approaches have emerged to provide faster onset of action compared with conventional immunosuppressive therapy, favourable tolerability profile and the potential for a sustained disease control for patients with gMG. Intravenous efgartigimod alfa (also known as efgartigimod alfa-fcab in the USA; Vyvgart^®) is the first neonatal Fc receptor antagonist approved in several countries worldwide, including the USA and EU for the treatment of gMG in adults who are anti-acetylcholine receptor (AChR) antibody positive, and in Japan for the treatment of gMG regardless of antibody status. In the pivotal clinical trial in patients with gMG, efgartigimod alfa rapidly reduced disease burden and improved muscle strength and quality of life. The beneficial effects of efgartigimod alfa occurred early and were durable and reproducible. Longer term, efgartigimod alfa provided consistent clinically meaningful improvements in patients with gMG. Efgartigimod alfa is generally well tolerated, with most adverse events being mild to moderate in severity. Thus, efgartigimod alfa is a novel, effective and generally well-tolerated treatment option for patients with gMG.

A Case of Statin-Associated Autoimmune Myopathy: Management and Treatment.

Elevated lipid panels are associated with an increased risk of cardiovascular disease. Management of heart disease with lipid lowering agents play a vital role in medicine. Statins are one group of medications that are widely utilized in the medical field to decrease the risk of atherosclerotic disease. Statins work by inhibiting the hepatic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Although statins are one of the most effective drugs for secondary and primary prevention of heart disease, they are not without risks and side effects such as hepatotoxicity and myopathy. We present a case of a male patient who developed progressively worsening muscle weakness and elevated muscle enzyme markers upon initiation of a statin. His symptoms persisted despite a trial of an alternative statin and subsequent discontinuation of all statin medications. A multitude of possible etiologies were considered and ranged from infectious, autoimmune, cancerous, to congenital in nature. Environmental factors, such as exposure to medications or toxins, were also considered as one of the possible precipitating factors. The association between his statin consumption and muscle weakness were not easily apparent at first. He required further workup including physical examination, electromyography, panel of myositis antibodies, and muscle biopsy. After clinical suspicion and elevated antibodies to HMGCR beyond the normal limit, he was discovered to have statin-associated autoimmune myopathy. The patient improved with the treatment of immunosuppressive agent's prednisone and methotrexate.

Association Between Rheumatic Autoantibodies and Immune-Related Adverse Events.

BACKGROUND: Side effects of immune checkpoint inhibitors (ICIs), called immune-related adverse events (irAEs), closely resemble primary autoimmune or rheumatic diseases. We aimed to understand the clinical utility of rheumatic autoantibodies (rhAbs) for diagnosing irAEs. PATIENTS AND METHODS: Patients without pre-existing autoimmune disease (pAID) who had cancer treated with ICI(s) treatment from 1/1/2011 to 12/21/2020 and a rhAb checked were retrospectively identified. Logistic regression assessed associations between autoantibodies and irAEs, cancer outcome, and survival. Specificity, sensitivity, and positive/negative predictive values (PPV, NPV) were estimated for key rhAbs and ICI-arthritis. Kaplan-Meier analyzed objective response rate (ORR) and overall survival (OS). RESULTS: A total of 2662 patients were treated with≥1 ICIs. One hundred and thirty-five without pAID had ≥ 1 rhAb tested. Of which 70/135(52%) were female; median age at cancer diagnosis was 62 years with most common cancers: melanoma (23%) or non-small cell lung cancer (21%), 96/135 (75%) were anti-PD1/PDL1 treated. Eighty had a rhAb ordered before ICI, 96 after ICI, and 12 before and after. Eighty-two (61%) experienced an irAE, 33 (24%) with rheumatic-irAE. Pre-ICI RF showed significant association with rheumatic-irAEs (OR = 25, 95% CI, 1.52-410.86, P = .024). Pre- and post-ICI RF yielded high specificity for ICI-arthritis (93% and 78%), as did pre- and post-ICI CCP (100% and 91%). Pre-ICI RF carried 93% NPV and pre-ICI CCP had 89% PPV for ICI-arthritis. No variables were significantly correlated with ORR. Any-type irAE, rheumatic-irAE and ICI-arthritis were all associated with better OS (P = .000, P = .028, P = .019). CONCLUSIONS: Pre-ICI RF was associated with higher odds of rheumatic-irAEs. IrAEs had better OS; therefore, clinical contextualization for rhAbs is critical to prevent unnecessary withholding of lifesaving ICI for fear of irAEs.

[Anti-MDA5 dermatomyositis. Literature review]. / Dermatomiositis anti-MDA5. Revisión de la literatura.

Dermatomyositis positive anti-melanoma differentiation-associated gene 5 (anti-MDA5 DM) is a rare disease that represents less than 2%. The prevalence of anti-MDA5 DM ranges from 7 to 60%, with higher prevalence in Asian (11-60%) and women. The clinical picture may be variable and is accompanied by the typical features of dermatomyositis, such as periorbital heliotrope (blue-purple) rash with edema, erythematous rash on the face, or the anterior chest (in a V-sign), and back and shoulders (in a shawl sign), violaceous papules or plaques located on the dorsal part of the metacarpophalangeal or interphalangeal joints, which are pathognomonic by definition; yet, one of the most striking signs is the painful ulceration skin that is found in 82% of cases, which is deep and in punching holes or showing hyperkeratotic crusts. For diagnosis is necessary the typical DM rashes (Gottron's papules or Gottron's sign and heliotrope rash), along with either an "interface dermatitis" skin pathology or evidence of myositis or a MSA (myositis-specific autoantibodies). Immunoprecipitation is the gold standard method to detect MSA. Combinations of glucocorticoids and immunosuppressants are used for treatment; besides, it is necessary the detection of rapidly progressive interstitial disease (RP-ILD) with a high-resolution CT because of its high association with fatal prognosis.

La dermatomiositis positiva contra el gen 5 asociado a la diferenciación de melanoma (DM anti-MDA5) es una enfermedad rara que representa menos del 2%. La prevalencia de DM anti-MDA5 varía de 7 a 60%, con mayor prevalencia en asiáticos (11-60%) y mujeres. El cuadro clínico es muy variado y se acompaña por las características típicas de dermatomiositis, como la eritema en heliotropo, con edema, exantema eritematoso en la cara o la parte anterior del tórax (signo de V) y en la espalda y los hombros (signo del chal), las pápulas de Gottron en la parte dorsal de las articulaciones metacarpofalángicas o interfalángicas, que son patognomónicas por definición, pero uno de los signos más llamativos es la ulceración cutánea dolorosa que se encuentra hasta en un 82% de los casos, es profunda y en sacabocados muestran costras hiperqueratósicas. Para el diagnóstico son necesarias las erupciones típicas de la DM (pápulas de Gottron o signo de Gottron y erupción de heliotropo), junto con una patología cutánea de "dermatitis de interfase" o evidencia de miositis o un MSA (autoanticuerpos específicos de miositis). La inmunoprecipitación es el método de referencia para detectar MSA. Para su tratamiento se usan combinaciones de glucocorticoides e inmunosupresores; ademas, es necesaria la detección de enfermedad intersticial rápidamente progresiva (RP-ILD) con tomografía computarizada de alta resolución por su alta asociación con un pronóstico fatal.