Comparison Chart

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Acronym Name SAID group Gene Inheritance Ethnicity Frequency Timing of symptoms Age of onset Skin cutaneous Neurologic Auditory Ophthalamic Cardiopulmonary Abdominal Lymphatic Joints bones muscles cartilage Vasculitis Amyloidosis Abnormal labs
Neonatal Onset Multisystem Autoinflammatory Disease - aka Chronic Infantile Neurological Cutaneous Articular Syndrome (NLRP3-AID-severe) Cryopyrin Associated Periodic Syndromes (CAPS) NLRP3-associated Autoinflammatory Diseases (NLRP3-AID) NLRP3 Autosomal dominant. Most cases are due to spontaneous mutations. Very few familial cases. [1] Any­, present in all races. [1] Estimated frequency 1:1 million, mostly due to spontaneous genetic mutations. [5] Continuous, with increased symptoms and fever during flares. [1] Chronic inflammation noted between flares. Neonatal/early infancy. Rash, symptoms, and abnormal labs are often present at birth. [1], [6] Ever-present, urticaria-like rash with increased neutrophils at the eccrine coils. Rash increases with flares. Some patients have cold-induced flares in addition to constant symptoms. [1] [4] A few with apthous ulcers. Negative ice cube test. Headaches, fever, fatigue, chronic aseptic meningitis, and elevated or high intracranial pressure (ICP). Papilledema is common. Many have mental delay and/or cognitive delay, impairments, or intellectual disability. A few have seizures. Strokes are rare. [6] Many have increased sensorineural hearing loss, starting in infancy/early childhood. [1], [6] Papilledema, uveitis, iritis, conjunctivitis. Some with retinal scarring, corneal haze or vision loss. [6], [26] Some may have a pericardial effusion, or pericarditis. [1] Some patients have hepatomegaly, splenomegaly, or hepatosplenomegaly. Nausea, vomiting and abdominal pain with flares, or with elevated intracranial pressure (ICP). [6] Splenomegaly. Many have generalized lymphadenopathy. [1] Joint pain, knee valgus or varus, limb length differences are common. Some have frontal bossing of the forehead, saddleback nose, contractures, and/or have clubbing of the fingers. [1] Short stature, growth delays, failure to thrive, arthritis, and osteopenia are often noted.[1],[26] <50% of patients knees or joints have bony overgrowth (usually on the patella) with chondrocytes that are not well differentiated, plus abnormal enchondral bone formation (no inflammatory cells), along with the premature fusion of physis. [79]. Vasculitis rarely develops. [1] Elevated SAA. Secondary amyloidosis in <2% pts. [1], [6] Chronically high: ESR, CRP, SAA, anemia, granulocytic leukocytosis. Many patients have elevated IgG, IgA and IgM [1], [6]
Familial Cold Autoinflammatory Syndrome (NLRP3-AID-mild) Cryopyrin Associated Periodic Syndromes (CAPS) NLRP3-associated Autoinflammatory Diseases (NLRP3-AID) NLRP3 Autosomal dominant. Many large family groups spanning generations. Some patients with spontaneous mutations. [1] Affects all races, but many are of European descent. [1] 1:1 million, or more. In USA 300+ diagnosed – most cases are from large family groups. [2], [5] Frequency of CAPS in France is 1:360,000. [55] 12-24 hours, or longer. Onset of fever and flares is often 1-3 hours after exposure to cold or cooling temperatures. [1] Infancy, but a few present with symptoms later in childhood or adolescence. [1] Cold-induced, urticaria-like rash with increased neutrophils at the eccrine coils. [4] Almost daily rash that increases with flares. [1] Ice cube test negative. A few with apthous ulcers. Some have headaches and fatigue with fever after cold exposure. It is unknown if there are any other effects on the central nervous system (CNS) at this time. [1] Some patients have mild hearing loss – not currently known if it‘s from CAPS inflammation. [1] Conjunctivitis (non-infectious) during flares. [1] Not noted. [1] Uncommon. [1] Not noted. [1] Arthralgia, stiffness and swelling with flares. [1] Not noted. [1] Elevated serum amyloid (SAA). Secondary amyloidosis in some patients. [1], [9] High: ESR, CRP, SAA. Leukocytosis with flares. [1]
Muckle-Wells Syndrome (NLRP3-AID-moderate) Cryopyrin Associated Periodic Syndromes (CAPS) NLRP3-associated Autoinflammatory Disease (NLRP3-AID) NLRP3 Autosomal dominant. Spontaneous mutations, and some family groups with MWS spanning generations. [1] Affects all races, but many are of European descent. [1] 1:1 million, but it may be more frequent. Some large family groups. [5] Frequency of CAPS in France is 1:360,000. [55] Often lasts 2-3 days. Random onset–flares of fever and symptoms are often triggered by cold or cooling temperature. [1] Infancy, but a few present with symptoms later in childhood or adolescence. [1] Urticaria-like rash with increased neutrophils at the eccrine coils. Rash and flares can be cold-induced, or from unknown triggers. [4] Most have a daily rash that increases with flares. [1] A few have apthous ulcers. Negative ice cube test. Some have headaches, fatigue with fever and flares. It is uncommon to have many other central nervous system symptoms. [1] A few patients have a MWS/NOMID crossover of symptoms. Many have increased sensorineural hearing loss, starting in adolescence. [1] Conjunctivitis (non-infectious) during flares,[1] or corneal haze. [26] MWS/NOMID crossover patients may have more eye involvement. Rare. [1] Some have abdominal pain with flares or other gastrointestinal issues. [1] Rarely noted. [1] Arthralgia, recurrent arthritis, stiffness and swelling with flares. [1] Not noted. [1] Elevated serum amyloid (SAA). >25 % with secondary amyloidosis. [1], [9] High: ESR, CRP, SAA. Leukocytosis with flares. [1]

Main authors:

Karen Durrant RN, BSN–President of The Autoinflammatory Alliance (autoinflammatory.org), & Dr Juan Ignacio Aróstegui MD–Immunologist at the CDB Hospital Clínic in Barcelona, Spain & Director of La Unidad de Enfermedades Autoinflamatorias (autoinflamatorias.com)

Acknowledgements: A special thanks to the many medical doctors who have helped to make voluntary suggestions in regards to the original comparative chart, and suggestions for our new Autoinflammatory Search Database: Dr Juan Ignacio Aróstegui, Dr Hal Hoffman, Dr Raphaela Goldbach-Mansky, Dr Scott Canna, Dr Anna Simon, Dr Polly Ferguson, Dr Rebecca Marsh, Dr Daniel Kastner, Dr Luca Cantarini, Dr Véronique Hentgen, Dr Nico M. Wulffraat, Dr Kieron Leslie, Dr Lori Broderick, Dr Mikail Kostik, Dr Beata Wolska, Dr Joost Frenkel, Dr Dan Kastner, Dr Helen Lachmann, Dr Jonathan Hausmann, Dr Phillip Kahn, Dr Israel Andrews, and to all that have been using our materials to educate others about autoinflammatory diseases worldwide.

Thank you to Black Peacock SE, especially David Schwieler, Tommy Westerberg and Lotti Ungerth Fastmarken for all your amazing work on this database. Also to Nathan Durrant and Jennifer Tousseau for all your help on this, the original chart, and many projects. Our deepest thanks to all of The Autoinflammatory Alliance Board of Directors, & to all the patients & families who have supplied images for this chart, & support for the Autoinflammatory Alliance. You are our greatest inspiration and strength!

Great thanks to all of the doctors from the International Society of Systemic Auto-Inflammatory Diseases (ISSAID) for their research & dedication to patients with autoinflammatory diseases, plus the opportunity to present the original chart in a poster session at the Autoinflammation 2013 Congress. Thanks for the inspiration for this chart also go to: The Translational Autoinflammatory Disease Section at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) & The National Human Genome Research Institute at the National Institutes of Health (NIH); The Spanish Society of Pediatric Rheumatology (SERPE) & La Unidad de Enfermedades Autoinflamatorias; The French Centre de Référence des Maladies Auto-inflammatoires (CeRéMAI) & Le Club Rhumatismes et Inflamations; Dermatology Online Atlas. (DermIS Dermatology Information System), the Pediatric Rheumatology European Society (PReS),European League Against Rheumatism(EULAR), PRINTO, the EUROFEVER Project, the SHARE Consortium, The National Amyloidosis Centre, UK, The Interuniversity autoinflammation workgroup & Nijmegen center for Immunodeficiency and Autoinflammation (NCIA) of the Radboud Nijmegen University Medical Center, Nijmegen, The Netherlands, The American College of Rheumatology (ACR), CARRA, FAVOR & the many other research centers and doctors around the world.

Disclosure: All of the doctors involved in the authorship, review, editing and creation of this chart voluntarily donated their help for this educational reference, & received no financial compensation. Karen Durrant, RN has only received reimbursement only for for out-of-pocket travel costs from SOBI to attend a few meetings as a patient representative, but has received no personal financial compensation from any pharmaceutical company.

Swedish Orphan Biovitrum AB (Sobi), of Stockholm, Sweden provided the Autoinflammatory Alliance with an unrestricted grant in 2014 to support the development of this Autoinflammatory Search Database to help to educate medical professionals, and a future collection of disease-specific websites for patients. This grant, along with donated funds from the general public and patient community has helped to make this monumental project a reality, and we are so thankful!

Novartis Pharmaceuticals Canada Inc. provided The NOMID Alliance (now known as the Autoinflammatory Alliance) with an unrestricted grant in 2012 to help with the initial development & printing costs for the first comparative chart in print. An unrestricted grant from Swedish Orphan Biovitrum AB (Sobi) in 2013 supported many projects, including: the printing of the final comparative chart that we distributed at the 2013 ACR meeting, and 2014 PRYSM meeting, in addition to mailings to doctors worldwide. The NOMID Alliance has received a number of unrestricted grants at various times from Regeneron, Novartis & Sobi for grant-specific projects.

List of abbreviations:

Autoinflammatory Chart References