Studies of the Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID / CAPS, DIRA, CANDLE, SAVI, CRMO, Still's Disease, Behcet's Disease, and Other Undifferentiated Autoinflammatory Diseases)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) ) Identifier:
First received: May 5, 2003
Last updated: September 29, 2015
Last verified: May 2015


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.


  • 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


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.

Nervous System Anomalies

Study Type: Observational
Official Title: Studies of the Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, SAVI, CRMO, Still s Disease, Behcet s Disease, and Other Undifferentiated Autoinflammatory Diseases)

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 99999999
Study Start Date: April 2003
Detailed 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). We recently identified a new autoinflammatory disease 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 including CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures), the spectrum CRMO (Chronic Recurrent Multifocal Osteomyelitis), Still s disease, and Beh(SqrRoot)(Beta)et s disease (BD) all of which may involve dysregulation of IL-1. In this research protocol we seek to comprehensively evaluate affected patients clinically, genetically, immunologically, and endocrinologically. In addition we intend to evaluate long term outcome and biomarkers. 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.


Ages Eligible for Study:   3 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

Subjects with known or suspected diagnosis of NOMID/CAPS, DIRA, CRMO, Still's disease, Behcet's disease, and other autoinflammatory diseases will be evaluated either at the outpatient or inpatient unit of the Clinical Center as indicated.

  • Patients with NOMID/CAPS or DIRA, 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 with other suspected autoinflammatory diseases

There is:

  • No age limit
  • 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.

Relatives of patients with autoinflammatory diseases or healthy volunteers may be included for genetic testing in collaboration with Dr. Daniel Kastner's laboratory. 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.


Active malignancy or any medical condition that in the opinion of the investigator would warrant exclusion

Inability to provide consent

Inability to return for follow up visits

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00059748

Contact: Robert A Colbert, M.D. (301) 443-8935

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Principal Investigator: Robert A Colbert, M.D. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  More Information

Additional Information:
Additional publications automatically indexed to this study by Identifier (NCT Number):

Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) ) Identifier: NCT00059748     History of Changes
Other Study ID Numbers: 030173, 03-AR-0173
Study First Received: May 5, 2003
Last Updated: September 29, 2015
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Central Nervous System Abnormalities
Neonatal Onset Multisystem Imflammatory

Additional relevant MeSH terms:
Joint Diseases
Nervous System Malformations
Congenital Abnormalities
Hypersensitivity, Immediate
Immune System Diseases
Musculoskeletal Diseases
Nervous System Diseases
Skin Diseases
Skin Diseases, Vascular processed this record on October 06, 2015