Study and Treatment of Inflammatory Muscle Diseases

• INCLUSION CRITERIA:

All eligible patients are invited to participate in this protocol. Patients are adults and minors, aged 16 or higher, with possible idiopathic muscle disease (suspected or confirmed). Since both men and women are affected with the disease, both sexes will be studied. All ethnic and racial groups are at risk and will be included. Pregnant women and women who intend to become pregnant during the study will be eligible since this disease affects both segments of the population. This protocol proposes responsible inclusion of pregnant women and the justification for this derives in part from the fact that women (who are suffering from autoimmune and rheumatic diseases) lack data from which to make informed decisions about health care during pregnancy.

INCLUSION OF PREGNANT WOMEN:

The majority of patients with autoimmune disease are women and of these individuals, the majority are of childbearing age. Furthermore, pregnancy is a risk factor for fluctuations in autoimmune disease activity, including organ- and life- threatening flares. The majority of our study population is comprised of women. The exclusion of women who become pregnant from systemic study by way of our natural history protocol, threatens both the well-being of the individual women (owing to the standard of care provision of the protocol) and the systematic discovery of pregnancy-specific data concerning the immunopathological basis of autoimmune disease. Skewed understanding from a restricted natural history study may leave vulnerable groups open to disproportionate harm owing to inequities in research. In other words, automatic disqualification due to pregnancy denies women agency in the issue of gender equity for access to research and in addition the systematic exclusion of pregnant women prevents generalizability of information to help under-resourced and marginalized populations, nationwide.

In summary,

• The cost of exclusion of pregnant women with myositis 1) insufficient evidence concerning how to manage such disease for the population, and 2) lack of access to the best myositis specific advice for individuals enrolled in the protocol who are unlikely to have access to specialty care outside of the NIH
• The cost of exclusion in research with regard to fetal safety derives from the fact that preeclampsia, eclampsia, preterm birth and miscarriage are higher in women who do not have access to subspecialty care. In this situation, reticence on the part of nonspecialists to treat active autoimmune disease during pregnancy or lack of access to appropriate treatment may lead to harm to women and their fetuses.
• The pregnant body possesses a unique hormonal and immunological environment. Similarly, it metabolizes medications in a manner different from non-pregnant women, let alone men. Hence, there is no reasonable path towards generating important biomedical knowledge other than to include pregnant women in this protocol.

The tension between protection by exclusion and the presumption of inclusion in research protocols has been specifically addressed by the US Institute of Medicine (now National Academy of Medicine) and the Task Force on Research Specific to Pregnant Women and Lactating Women to advise the Secretary of Health and Human Services regarding gaps in knowledge and research on safe and effective therapies for pregnant and lactating women, and both have both weighed in as favoring the presumption of inclusion (https://www.nichd.nih.gov/about/advisory/PRGLAC). Our study falls in line with these position papers since it is responsible (it benefits, patients and their fetuses and provides relevant data to the population at large) and because it is low risk (it is standard of care, only, and does not invoke experimental interventions).

Healthy volunteers will be eligible only if they are adults aged 18 or older and only if they are willing to provide informed consent. There is no benefit to the healthy volunteers; however their inclusion will provide invaluable information in comparison to the patients for the purpose of research. Recruitment of healthy volunteers has been completed.

Participation of NIH Staff or family members of study team members

NIH staff and family members of study team members may be enrolled in this study as this population meets the study entry criteria. Neither participation nor refusal to participate as a subject in the research will have an effect, either beneficial or adverse, on the participant s employment or position at NIH.

Every effort will be made to protect participant information, but such information may be available in medical records and may be available to authorized users outside of the study team in both an identifiable an unidentifiable manner.

The NIH Information Sheet on NIH Staff Research Participation will be made available. Please see section for consent of NIH Staff.

EXCLUSION CRITERIA:

• Children (age less than 16 years) are excluded
• Subjects with severe active infection (such as requiring intravenous antibiotics) or other co-morbidities that in the opinion of the investigator would warrant exclusion.
• Subjects or their legal guardians who are unable or unwilling to give informed consent/assent.