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)
| Status: | Recruiting |
|---|---|
| Conditions: | Skin and Soft Tissue Infections, Lymphoma, Neurology, Orthopedic, Endocrine, Dermatology |
| Therapuetic Areas: | Dermatology / Plastic Surgery, Endocrinology, Neurology, Oncology, Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | Any - 100 |
| Updated: | 4/6/2019 |
| Start Date: | April 30, 2003 |
| Contact: | Robert A Colbert, M.D. |
| Email: | colbertr@mail.nih.gov |
| Phone: | (301) 443-8935 |
Studies of Natural History, Pathogenesis, and Outcomes in Autoimmune and Inflammatory Diseases Including Juvenile Dermatomyositis
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.
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.
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.
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.
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.
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.
- 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:
- 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.
- 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
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
Click here to add this to my saved trials
