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)

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief 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.

Condition or disease
Urticaria; Arthropathy; Lymphadenopathy; Nervous System Anomalies

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). 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. 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.

Study Design

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Observational
Estimated Enrollment :	99999999 participants
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)
Study Start Date :	April 30, 2003

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	3 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

• INCLUSION CRITERIA:
• Patients with NOMID / CAPS or DIRA, CANDLE, SAVI, 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 to the protocol whenever possible.

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 provide consent
• Inability to return for follow up visits

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Robert A Colbert, M.D.	(301) 443-8935	colbertr@mail.nih.gov

Locations

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 Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 prpl@cc.nih.gov

Sponsors and Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Investigators

Principal Investigator:	Robert A Colbert, M.D.	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications:

Han S, Lin YC, Wu T, Salgado AD, Mexhitaj I, Wuest SC, Romm E, Ohayon J, Goldbach-Mansky R, Vanderver A, Marques A, Toro C, Williamson P, Cortese I, Bielekova B. Comprehensive immunophenotyping of cerebrospinal fluid cells in patients with neuroimmunological diseases. J Immunol. 2014 Mar 15;192(6):2551-63. doi: 10.4049/jimmunol.1302884. Epub 2014 Feb 7.

Sibley C, Yazici Y, Tascilar K, Khan N, Bata Y, Yazici H, Goldbach-Mansky R, Hatemi G. Behçet syndrome manifestations and activity in the United States versus Turkey -- a cross-sectional cohort comparison. J Rheumatol. 2014 Jul;41(7):1379-84. doi: 10.3899/jrheum.131227. Epub 2014 Jun 15.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rodriguez-Smith J, Lin YC, Tsai WL, Kim H, Montealegre-Sanchez G, Chapelle D, Huang Y, Sibley CH, Gadina M, Wesley R, Bielekova B, Goldbach-Mansky R. Cerebrospinal Fluid Cytokines Correlate With Aseptic Meningitis and Blood-Brain Barrier Function in Neonatal-Onset Multisystem Inflammatory Disease: Central Nervous System Biomarkers in Neonatal-Onset Multisystem Inflammatory Disease Correlate With Central Nervous System Inflammation. Arthritis Rheumatol. 2017 Jun;69(6):1325-1336. doi: 10.1002/art.40055. Epub 2017 May 10.

Chang Z, Spong CY, Jesus AA, Davis MA, Plass N, Stone DL, Chapelle D, Hoffmann P, Kastner DL, Barron K, Goldbach-Mansky RT, Stratton P. Anakinra use during pregnancy in patients with cryopyrin-associated periodic syndromes (CAPS). Arthritis Rheumatol. 2014 Nov;66(11):3227-32.

Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE, Sanchez GAM, Tenbrock K, Wittkowski H, Jones OY, Kuehn HS, Lee CR, DiMattia MA, Cowen EW, Gonzalez B, Palmer I, DiGiovanna JJ, Biancotto A, Kim H, Tsai WL, Trier AM, Huang Y, Stone DL, Hill S, Kim HJ, Hilaire CS, Gurprasad S, Plass N, Chapelle D, Horkayne-Szakaly I, Foell D, Barysenka A, Candotti F, Holland SM, Hughes JD, Mehmet H, Issekutz AC, Raffeld M, McElwee J, Fontana JR, Minniti CP, Moir S, Kastner DL, Gadina M, Steven AC, Wingfield PT, Brooks SR, Rosenzweig SD, Fleisher TA, Deng Z, Boehm M, Paller AS, Goldbach-Mansky R. Activated STING in a vascular and pulmonary syndrome. N Engl J Med. 2014 Aug 7;371(6):507-518. doi: 10.1056/NEJMoa1312625. Epub 2014 Jul 16.

Aksentijevich I, Masters SL, Ferguson PJ, Dancey P, Frenkel J, van Royen-Kerkhoff A, Laxer R, Tedgård U, Cowen EW, Pham TH, Booty M, Estes JD, Sandler NG, Plass N, Stone DL, Turner ML, Hill S, Butman JA, Schneider R, Babyn P, El-Shanti HI, Pope E, Barron K, Bing X, Laurence A, Lee CC, Chapelle D, Clarke GI, Ohson K, Nicholson M, Gadina M, Yang B, Korman BD, Gregersen PK, van Hagen PM, Hak AE, Huizing M, Rahman P, Douek DC, Remmers EF, Kastner DL, Goldbach-Mansky R. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med. 2009 Jun 4;360(23):2426-37. doi: 10.1056/NEJMoa0807865.

Responsible Party:	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ClinicalTrials.gov Identifier:	NCT00059748 History of Changes
Other Study ID Numbers:	030173; 03-AR-0173
First Posted:	May 6, 2003
Last Update Posted:	April 2, 2018
Last Verified:	January 9, 2018

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) ):

Central Nervous System Abnormalities; Arthropathy; Urticaria; Papilledema	Autoinflammation; Neonatal Onset Multisystem Imflammatory; Disease; NOMID

Additional relevant MeSH terms:

Hereditary Autoinflammatory Diseases; Urticaria; Joint Diseases; Lymphadenopathy; Behcet Syndrome; Nervous System Malformations; Skin Diseases, Vascular; Skin Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Musculoskeletal Diseases; Lymphatic Diseases; Mouth Diseases	Stomatognathic Diseases; Uveitis, Anterior; Panuveitis; Uveitis; Uveal Diseases; Eye Diseases; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Nervous System Diseases; Congenital Abnormalities