Studies of the Natural History Pathogenesis and Outcome of Autoinflammatory Diseases Including Juvenile Dermatomyositis

  • STATUS
    Recruiting
  • participants needed
    5000
  • sponsor
    National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Updated on 4 August 2021
blood tests
deficiency
x-rays
il-1
skin disease
inflammatory disease
computerized tomography
dermatomyositis
skin inflammation

Summary

Purpose

The purpose of this protocol is 1. To comprehensively evaluate patients with autoinflammatory diseases clinically, genetically and immunologically at the autoinflammatory disease clinic at the NIH. 2. To follow patients with autoinflammatory Diseases that are genetically defined including Neonatal-Onset Multisystem Inflammatory Disease (NOMID), the most severe clinical phenotype of Cryopyrin-Associated Periodic Syndromes (CAPS), Deficiency of IL-1 Receptor Antagonist (DIRA), Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperatures (CANDLE), and STING-Associated Vasculopathy with onset in Infancy (SAVI), and those with genetically undefined autoinflammatory disorders to determine long-term disease outcomes. 3. To develop biomarkers that help us assess disease activity and response to treatment. 4. To assess the eligibility of affected patients for inclusion in ongoing and planned treatment protocols.

Goal: The goals of our studies are to understand the underlying immune dysregulation, to identify the genetic cause and to translate our findings into novel treatments that improve patients disease outcome.

Eligibility
  • Patients with known NOMID/CAPS, DIRA, CANDLE, SAVI, CRMO, Still's Disease, and with other yet undifferentiated autoinflammatory diseases.
  • Healthy adult and pediatric relatives.
  • Volunteers
Design

Participants will be evaluated at the NIH for 2-5 days. All participants will have a detailed medical history, physical exam, blood tests and other evaluations depending on the extend of their autoinflammatory disease.

Participants may also expect the following assessments:

  1. Clinical test that help assess organ damage and functional impact such as hearing vision, memory and learning tests.
  2. Imaging studies to characterize the organ involvement of the inflammatory disease including: X-rays, CT scans, special MRIs, bone scans.
  3. Laboratory evaluations including clinical markers of disease activity, research samples for genetic studies, and blood samples for cytokine/biomarker assessment, and gene expression profiling.<TAB>
  4. Completion of questionnaires to assess disease activity and quality of life.
  5. If indicated, other procedures may be administered that include: a lumbar puncture if CNS inflammation is suspected and a skin biopsy if skin inflammation is present. other gastrointestinal procedures as they are clinically indicated.
  6. Patients my have a research skin biopsy taken.

Participants may return for a single follow-up visits or for long term-follow up depending on their disease and willingness to be followed long-term.

Description

Autoinflammatory multisystem diseases are a group of diseases that are characterized by recurrent episodes of systemic inflammation as well as organ specific inflammation that can involve the skin, eyes, joints, bones, serosal surfaces, inner ear, and brain. The prominent role of IL-1 in the pathogenesis of these disorders has first become evident through the discovery of mutations in CIAS1 causing the cryopyrin-associated periodic syndromes (CAPS) including the most severe presentation Neonatal Onset Multisystem Inflammatory Disease (NOMID). Over the years we identified additional autoinflammatory diseases including DIRA (Deficiency of IL-1 Receptor Antagonist), a disease that is caused by mutations in IL1RN. Therapy with anakinra, the IL-1 receptor antagonist, can be life-saving. We also study additional rare diseases not IL-1 mediated including CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures) caused by mutations in proteasome components, and recently SAVI (STING associated vasculopathy with onset in infancy) caused by mutations in TMEM173, and juvenile dematomyositis (JDM) which shares some phenotypic features as well as an interferon (IFN) signature with SAVI and CANDLE. Many additional autoinflammatory phenotypes have no genetic causes, including autoinflammatory disorders that are not even clinically defined. Clinical conditions including the spectrum CRMO (Chronic Recurrent Multifocal Osteomyelitis), Still s disease, and Beh(SqrRoot)(Beta)et s disease (BD) with possible involvement of IL-1 dysregulation are also of interest.. In this research protocol we seek to comprehensively evaluate affected patients clinically, genetically, immunologically, and endocrinologically. In addition we intend to evaluate longterm outcomes and biomarkers over the time of observations. Eligibility for ongoing and planned treatment protocols will be determined by screening patients in this protocol. We plan to evaluate patients on a consultative basis for other autoinflammatory diseases for possible enrollment into this study.

Details
Condition Arthropathy, Dermatomyositis, Lymphadenopathy, Urticaria, CONNECTIVE TISSUE DISEASE, Cranioschisis, Dermatosis, Polymyositis, Hives (Urticaria), Dermatomyositis (Connective Tissue Disease), Congenital Skin Diseases, Polymyositis (Inflammatory Muscle Disease), Skin Conditions, Autoinflammatory Disease, Connective Tissue Diseases, juvenile dermatomyositis
Clinical Study IdentifierNCT00059748
SponsorNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Last Modified on4 August 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Patients with NOMID / CAPS or DIRA, CANDLE, SAVI, CRMO, Still's diseases, Behet's disease, JDM who are mutation positive for the disease or fulfill clinical criteria of the disease
Patients who have non-infectious osteolytic bone lesions
Patients who fulfill criteria for definite or probable Still s disease
Patients who fulfill criteria for definite or probable Behcet s disease
Patients who fulfill criteria for definite or probable JDM
Patients with other suspected autoinflammatory diseases
There is
years old or older
Patients or their legal guardians need to be able and willing to give informed consent and a pediatric patient needs to be willing to assent to the protocol whenever possible
No exclusion based on pregnancy status
Relatives of patients with autoinflammatory diseases or healthy volunteers may
be included for genetic testing. The genetic evaluations will be conducted in
collaboration with Dr. Fleisher s laboratory at the Clinical Center laboratory
and other groups. See genetics consent form. We may also collect blood for
serum and RNA analyses to establish a cohort of healthy controls that is
matched in age, gender and ethnicity to the study patients. Skin biopsies for
research may be requested from patients, patient relatives and healthy
volunteers

Exclusion Criteria

Active malignancy or any medical condition that in the opinion of the investigator would warrant exclusion
Inability to return for follow up visits
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Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

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If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

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