• Resumen
  • Sinónimos
  • Signos y Síntomas
  • Causas y Herencia
  • Frecuencia
  • Enfermedades con síntomas similares
  • Diagnóstico
  • Tratamiento
  • Investigaciones
  • Referencias
  • Programas & Recursos
  • Informe completo

Antisynthetase Syndrome

Imprimir

Última actualización: 1/24/23
Años publicados: 2018, 2023


Reconocimiento

NORD gratefully acknowledges Frederick W. Miller, MD, PhD, Scientist Emeritus, National Institutes of Health, former Chief, Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, for assistance in the preparation of this report.


Resumen

Antisynthetase syndrome is a rare, chronic disorder that can affect multiple systems of the body. The disorder is immune-mediated, which means there is inflammation resulting from abnormal functioning of the immune system and the presence of specific autoantibodies that target specific proteins in the body. The symptoms and severity of the disorder can vary greatly among affected individuals. Common symptoms include inflammation of the muscles (myositis), inflammation of several joints (polyarthritis), interstitial lung disease and thickening and cracking (fissuring) and discoloration of the skin of the fingers, called mechanic’s hands). Some individuals develop pain and numbness or a prickly feeling in the fingers and toes in response to cold (Raynaud phenomenon). During a Raynaud episode, the fingers or toes may turn white or blue.

Affected individuals can also have nonspecific symptoms like fatigue, unexplained fevers and unintended weight loss. The exact, underlying cause is not fully understood, but some genetic and environmental risk factors have been identified. Antisynthetase syndrome sometimes occurs along with other conditions such as uncommon inflammatory muscle diseases like dermatomyositis or polymyositis.

  • Sección siguiente >
  • < Sección anterior
  • Sección siguiente >

Sinónimos

  • anti-synthetase syndrome
  • AS syndrome
  • ASSD
  • < Sección anterior
  • Sección siguiente >
  • < Sección anterior
  • Sección siguiente >

Signos y Síntomas

The signs and symptoms can vary greatly from one person to another. Every person is unique and how the disorder will affect them can be very different. Symptoms can develop rapidly. Affected individuals will usually not have all of the symptoms discussed below. For example, some affected individuals will have little muscle involvement, but prominent signs of lung disease. Muscle disease, interstitial lung disease and arthritis are generally considered the three main symptoms of this disorder (the classic triad), but they may not develop at the same time.

Antisynthetase syndrome can affect the muscles. Muscle inflammation (myositis), muscle pain (myalgia) and muscle stiffness is common. These abnormalities can lead to muscle weakness. Inflammation of several joints of the body (polyarthritis) may also occur. Polyarthritis is associated with pain and stiffness of the affected joints. The surrounding bone is usually not affected (non-erosive arthritis).

Some individuals develop interstitial lung disease, which is characterized by progressive inflammation and scarring of the lungs, particularly of the tissue and space around the tiny air sacs, or alveoli. This area is called the interstitium. This can lead to shortness of breath and coughing. In some instances, progressive damage to the lungs can lead to respiratory insufficiency (when the lungs cannot deliver sufficient levels of oxygen to the body) requiring oxygen treatment and, eventually, life-threatening respiratory failure.

Nonspecific symptoms can also occur including unexplained fevers, fatigue, loss of appetite, unintended weight loss, difficulty swallowing (dysphagia) and skin rashes including a heliotropic rash, a distinctive reddish-purple rash on the upper eyelid or across the cheeks and bridge of the nose in a ‘butterfly’ pattern.

  • < Sección anterior
  • Sección siguiente >
  • < Sección anterior
  • Sección siguiente >

Causas y Herencia

The exact cause of antisynthetase syndrome is not fully understood. Affected individuals have autoantibodies. Antibodies are part of the immune system; they are specialized proteins that target foreign or invading organisms. Autoantibodies are antibodies that mistakenly attack healthy tissue. In antisynthetase syndrome, affected individuals have autoantibodies that target certain enzymes in the body called aminoacyl-tRNA synthetases. Enzymes are specialized proteins that help to bring about specific biochemical reactions in the body and aminoacyl-tRNA synthetases help to regulate the production of other proteins and are important for the overall health and function of the body. Researches do not know why these autoantibodies target aminoacyl-tRNA synthetases. Not every person who develops these autoantibodies will go on to develop symptoms of antisynthetase syndrome.

The exact role these autoantibodies play in the development of antisynthetase syndrome is not fully understood. The autoantibodies that have identified in this disorder include anti-Jo1, anti-EJ, anti-OJ, anti-PL7, anti-PL12, anti-SC, anti-KS, anti-JS, anti-HA, anti-YRS, anti-tryptophanyl and anti-Zo, and each of these target a different aminoacyl-tRNA synthetase. Anti-Jo1 is the most common autoantibody in individuals with antisynthetase syndrome.

Some autoantibodies are more likely to be associated with specific symptoms. Muscle disease occurs more often with anti-Jo1 or anti-PL7. Interstitial lung disease occurs more often with anti-PL7, anti-PL12, anti-KS and anti-OJ autoantibodies. Some individuals with anti-OJ autoantibodies have developed severe muscle weakness.

These autoantibodies are believed to be produced after a ‘triggering’ event such as a viral infection or exposure to certain drugs. When the immune system responds to these triggering events, something goes wrong, and these autoantibodies are created that could then damage healthy tissue.

Some affected individuals may have a genetic predisposition to developing antisynthetase syndrome. A genetic predisposition means that a person may carry a gene or genes for a particular condition, but the condition will not develop unless other factors help to trigger the disease. Most likely, antisynthetase syndrome is a multifactorial disease, in which multiple factors including immune, genetic and environmental ones are necessary for the development of the disorder.

  • < Sección anterior
  • Sección siguiente >
  • < Sección anterior
  • Sección siguiente >

Frecuencia

Antisynthetase syndrome is a rare disorder that affects females twice as often as males. Age of onset can range from the late teens to the elderly, with a mean average of the 50s. The exact incidence or prevalence of the disorder is unknown. Because rare disorders often go undiagnosed or misdiagnosed, determining the true frequency of antisynthetase syndrome in the general population is difficult.

  • < Sección anterior
  • Sección siguiente >
  • < Sección anterior
  • Sección siguiente >

Diagnóstico

A diagnosis of antisynthetase syndrome is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and tests that confirm the presence of autoantibodies against the one of the aminoacyl-tRNA synthetase enzymes.

 

Clinical Testing and Workup

Blood tests can reveal the presence of autoantibodies against one of the aminoacyl-tRNA synthetase enzymes. Every person who has one of these autoantibodies does not, necessarily, develop antisynthetase syndrome. There are published criteria that have been proposed to help with diagnosis. However, these criteria are not universally accepted, and some physicians think some people may have antisynthetase syndrome even if they do not meet the requirements for diagnosis under these guidelines. Based on some of the guidelines, affected individuals must also have two major criteria or one major criterion, or two minor criteria of the disorder. The two major criteria are interstitial lung disease and muscle disease. Minor criteria are arthritis, Raynaud phenomenon or thickening and cracking of the skin of the hands (mechanic’s hands).

Blood tests can also reveal elevated levels of creatine kinase or aldolase, which are muscle enzymes. When these muscle enzymes are elevated, it is a sign of muscle damage. This is not specific to antisynthetase syndrome, and is a sign of many different types of muscle disease.

A specialized imaging technique called high resolution computerized tomography (CT) scanning may be used to detect and evaluate lung disease. During CT scanning, a computer and x-rays are used to create cross-sectional images of certain tissue structures. High resolution CT scanning involves specific techniques that enhance or improve the resolution of the images. Pulmonary function tests may be administered to determine how well or poorly the lungs are working.

Specialized testing that records electrical activity in skeletal muscle at rest and during muscle contraction (electromyography [EMG]) may be performed to determine the health of the muscles.

  • < Sección anterior
  • Sección siguiente >
  • < Sección anterior
  • Sección siguiente >

Tratamiento

Treatment
The treatment of antisynthetase syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. General internists, specialists in the diagnosis and treatment of lung diseases (pulmonologists), specialists in the diagnosis and treatment of skeletal and muscle diseases (rheumatologists, neurologists, or orthopedists), specialists in the diagnosis and treatment of immunological diseases (immunologists) and other healthcare professionals may need to plan an affected person’s treatment systematically and comprehensively. Psychosocial support for the entire family is essential as well.

There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with antisynthetase syndrome.

Affected individuals may be treated with drugs that help to reduce inflammation called corticosteroids or drugs that suppress the activity of the immune system (immunosuppressive drugs). The effectiveness of these treatments and the amount of time an individual must remain on these medications will vary.

A drug called hydroxychloroquine has been used to treat skin symptoms.

Physical therapy is recommended to help to treat muscle disease by increasing muscle strength and reducing muscle wasting.

  • < Sección anterior
  • Sección siguiente >
  • < Sección anterior
  • Sección siguiente >

Investigaciones

Some of the drugs that have been used to treat affected individuals include azathioprine, methotrexate, cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil or rituximab. More research is necessary to determine the long-term safety and effectiveness of these medications for the treatment of antisynthetase syndrome.

Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/

For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

  • < Sección anterior
  • Sección siguiente >
  • < Sección anterior
  • Sección siguiente >

Referencias

JOURNAL ARTICLES
Zanframundo G, Faghihi-Kashani S, Scire CA, et al. Defining anti-synthetase syndrome: a systematic literature review. Clin Exp Rheumatol. 2022 Feb;40(2):309-319. https://pubmed.ncbi.nlm.nih.gov/35225224/

Meyer A, Lannes B, Goetz J, et al. Inflammatory myopathies: a new landscape. Joint Bone Spine. 2018;85:23-33. https://www.ncbi.nlm.nih.gov/pubmed/28343013

Gonzalez-Gay MA, Montecucco C, Selva-O’Callaghan A, et al. Timing of onset affects arthritis presentation pattern in antisynthetase syndrome. Clin Exp Rheumatol. 2018;36:44-49. https://www.ncbi.nlm.nih.gov/pubmed/28770709

Castaneda S, Cavagna L, Gonzalez-Gay MA, AENEAS (American-European Network of Antisynthetase Syndrome) collaborative groups members. Comments on the “2017 Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies and Their Major Subgroups.” Points of Concern. Arthritis Rheumatol. 2018;[Epub ahead of print].

Noguchi E, Uruha A, Suzuki S, et al. Skeletal muscle involvement in antisynthetase syndrome. JAMA Neurol. 2017;74:992-999. https://www.ncbi.nlm.nih.gov/pubmed/28586844

Bartoloni E, Gonzazlez-Gay MA, Scire C, et al. Clinical follow-up predictors of disease pattern change in anti-Jo1 positive anti-synthetase syndrome: results from a multicenter, international and retrospective study. Autoimmune Rev. 2017;16:253-257. https://www.ncbi.nlm.nih.gov/pubmed/28147261

Witt LJ, Curran JJ, Strek ME. The diagnosis and treatment of antisynthetase syndrome. Clin Pulm Med. 2016;23:218-226. https://www.ncbi.nlm.nih.gov/pubmed/27594777

Zamora AC, Hoskote SS, Abascal-Bolado B, et al. Clinical features and outcomes of interstitial lung disease in anti-Jo-1 positive antisynthetase syndrome. Respir Med. 2016;118:39-45. https://pubmed.ncbi.nlm.nih.gov/27578469/

Mahler M, Miller FW, Fritzler MJ. Idiopathic inflammatory myopathies and the anti-synthetase syndrome: a comprehensive review. Autoimmun Rev. 2014;13:367-371. https://www.ncbi.nlm.nih.gov/pubmed/24424190

Sem M, Molberg O, Lund MB, Gran JT. Rituximab treatment of the anti-synthetase syndrome: a retrospective case series. Rheumatology (Oxford). 2009;48:968-971. https://www.ncbi.nlm.nih.gov/pubmed/19531628

INTERNET
Miller ML, Vleugels RA. Clinical manifestations of dermatomyositis and polymyositis in adults. UpToDate, Inc. May 4, 2022. Available at: https://www.uptodate.com/contents/clinical-manifestations-of-dermatomyositis-and-polymyositis-in-adults Accessed Jan 19, 2023.

Genetic and Rare Disease Information Center. Antisynthetase Syndrome. Nov 8, 2021. Available at: https://rarediseases.info.nih.gov/diseases/735/antisynthetase-syndrome#ref_9478 Accessed Jan 19, 2023.

Benveniste O. Antisynthetase Syndrome. Orphanet. Feb 2021.Available at: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=81 Accessed Jan 19, 2023.

The Myositis Association. What is Antisynthetase syndrome? Available at: https://www.myositis.org/learn-about-myositis/faqs/539-what-is-antisynthetase-syndrome Accessed Jan 19, 2023.

American Thoracic Society. Interstitial Lung Disease. Available at: https://www.thoracic.org/statements/insterstitial-lung-disease.php Accessed Jan 19, 2023.

  • < Sección anterior
  • Sección siguiente >

Programas & Recursos

Programas de asistencia RareCare®

Programas de Asistencia Adicional

Programa de Asistencia MedicAlert

NORD y la Fundación MedicAlert se han asociado en un nuevo programa para brindar protección a pacientes con enfermedades raras en situaciones de emergencia.

Aprende más https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/

Programa de Apoyo Educativo de Enfermedades Raras

Asegurarse de que los pacientes y los cuidadores estén equipados con las herramientas que necesitan para vivir su mejor vida mientras manejan su condición rara es una parte vital de la misión de NORD.

Aprende más https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/

Programa de descanso para cuidadores raros

Este programa de asistencia, primero en su tipo, está diseñado para los cuidadores de un niño o adulto diagnosticado con un trastorno raro.

Aprende más https://rarediseases.org/patient-assistance-programs/caregiver-respite/

Organizaciones de pacientes


National Organization for Rare Disorders