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.
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
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. 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, 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
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
- 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