• INCLUSION CRITERIA - AFFECTED PARTICIPANTS:
  1. Be 3 to 99 years old for participants who will be seen at the NIH CC; be 0 (newborn) to 99 years old for participants who will submit mail-in samples. (Participants younger than 3 years will not be seen at the NIH CC.)
  2. Is willing to allow storage of biological specimens for future use in medical research.
  3. Is willing to allow genetic testing on collected biological samples.
  4. Has a primary care or other physician who will manage all health conditions related or unrelated to the study objectives.
  5. Fulfills one of the following criteria:
     • Has a known disease-causing genetic mutation associated with NOMID/CAPS, DIRA, CANDLE, SAVI, or NLRC4-MAS.
     • Has clinical signs or symptoms not explained by any other disorder (eg, infections, malignancies) and are consistent with a possible IL-1 mediated autoinflammatory disease. Participants must meet both of the following criteria:
       • Clinical characteristics strongly consistent with an IL-1 mediated autoinflammatory disease per the following criteria and at the discretion of the principal investigator (PI). Individuals must have a past or present history of one of the following to be considered for study enrollment:
         • Recurrent fever that has gone undiagnosed after reasonable attempts, and that is consistent with the conditions under study in this protocol
         • Neutrophilic urticaria, pustular dermatitis, erysipelas-like erythema, or urticarial rash
         • Epiphyseal and/or patella enlargement, periostitis, myalgias, arthralgias, arthritis, or recurrent multifocal aseptic osteomyelitis
         • Sensorineural hearing loss
         • Chronic aseptic meningitis or CNS vasculitis
         • Conjunctivitis, episcleritis, uveitis, papilledema, pleuritis, pericarditis, aseptic peritonitis, early onset enterocolitis, hepatosplenomegaly, or lymphadenopathies
       • Laboratory characteristics strongly consistent with an IL-1mediated autoinflammatory disease per the following criteria. Individuals must havepast or present history of evidence of systemic inflammation (eg, elevation of C-reactive protein [CRP] and/or erythrocyte sedimentation rate [ESR], anemia, thrombocytosis).
     • Has clinical signs or symptoms not explained by any other disorder (eg, infections, malignancies) and are consistent with a possible IFN-mediated, autoinflammatory disease.1,36 Participants must meet both of the following criteria:
       • Clinical characteristics strongly consistent with an IFN-mediated autoinflammatory disease per the following criteria and at the discretion of the PI. Individuals must have a past or present history of one of the following to be considered for study enrollment:
         • Recurrent fevers that has gone undiagnosed after reasonable attempts, and that is consistent with the conditions under study in this protocol
         • Panniculitis, ischemic ulcerative skin lesions, chilblain lesions, or livedo reticularis
         • Lipodystrophy
         • Myositis, arthralgias, arthritis, or joint contractures
         • Basal ganglia calcifications or white matter CNS disease
         • Interstitial lung disease, lung fibrosis, or pulmonary hypertension
         • Conjunctivitis, episcleritis, cortical blindness, glaucoma, papilledema, or hepatosplenomegaly
         • Laboratory characteristics strongly consistent with an IFN-mediated autoinflammatory disease per the following criteria. Individuals must have past or present history one or more of the following to be considered for study enrollment:
         • Evidence of systemic inflammation (eg, ESR or CRP)
         • Cytopenias (eg. leukopenia, anemia, or thrombocytopenia)
         • Dyslipidemia or insulin resistance
         • Abnormal liver function test, creatinine kinase (CK), or LDH
     • Has clinical signs or symptoms consistent with an undifferentiated autoinflammatory disease (including but not limited to dysregulation in other proinflammatory cytokines such as IL-17, TNF, IL-18, and others). Participants must meet one of the following criteria:
       • Clinical characteristics strongly consistent with an undifferentiated autoinflammatory disease. Individuals must have a past or present history of one of the clinical and one of the laboratory characteristics mentioned above to be considered for study enrollment.
       • Individuals with defined organ inflammation associated with past or current evidence of systemic inflammation.
  6. Alternatively to #5, be currently enrolled as an affected participant on NIAMS study 03-AR-0173.

INCLUSION CRITERIA - UNAFFECTED RELATIVES OF AFFECTED PARTICIPANTS:

1. Be 3 to 99 years old for participants who will be seen at the NIH CC; be 0 (newborn) to 99 years old for participants who will submit mail-in samples.
2. Be related by blood to an affected participant.
3. Is willing to allow storage of biological samples for future use in medical research.
4. Is willing to allow genetic testing on collected biological samples.
5. Does not fulfill any of inclusion criterion #5 for affected participants.

INCLUSION CRITERIA - HEALTHY VOLUNTEERS:

1. Be at least 18 years old.
2. Not be related to an affected participant.
3. s willing to allow storage of biological samples for future use in medical research.
4. Is willing to allow genetic testing on collected biological samples.
5. Does not fulfill any of inclusion criterion #5 for affected participants.

EXCLUSION CRITERIA:

1. Presence of conditions that, in the judgment of the investigator, may put the participant at undue risk or make them unsuitable for participation in the study.
2. Oncological evaluation suggestive of lymphoma or leukemia.