Comparison Chart of Systemic Autoinflammatory Diseases …

1 SLC29A3 relatedCryopyrin-Associated Periodic Syndromes (CAPS)GranulomatousInflammatory Bone DiseasesProtein FoldingIdiopathicProteasome Macrophage Activation DiseasesMevalonate Kinase DeficienciesPyrinPyogenic DiseasesMonarch-1 (Primary) Familial Hemophagocytic Lymphohistiocy-tosis aka Familial ErythrophagocyticLymphohistiocytosisPRF1 , STX11, STXBP2, MUNC13-4 , RAB27A X link: SH2D1A, BIRC4 Autosomal recessive,but if X-linked: inheri-tance is all races. 80% of African Americans, & 20% of pts. w/European decent have PRF1 ,481 HLH affects 1:50,000 people often > 39 C 1-2 times/day for >2 weeks, most often occurring in the evening w/arthralgia, rash & other ,48 Onset <1yr: often by 6 months early childhood. Some in utero or late childhood. A few adult-onset ,48,4940% w/transient maculopapular, nodular or purpuric skin rashes during bouts of high fever. ,48 High fevers. Increased CSF protein. High ICP. Multifocal inflammation of the gray & white matter, intracranial bleeding, generalized atrophy or brain edema, seizures &/or : ESR, CRP, triglycer-ides, LFTs, soluble CD25, ferritin.

2 Low: platelets, fibrinogen. Low NK cell cytotoxic function, neutropenia, risk for respiratory infections triggering fevers, Systemic inflam-mation & MAS. Hemophago-cytosis spleen/lymph nodes. Enlarged liver &/or disease is common. High risk of death from multi-organ failure in 2+ months if in the bone marrow. Delayed closure of the bones of the skull in infants, bulg-ing fontanel often noted. Neck stiffness, abnormal muscle tone, impaired muscle coordination, ,49 Not ,48,49 Not ,48,49 Blindness due to CNS ,48,49 Generalized purpuric ma-cules in Familial HLH. (Arch Dermatol. 2002;138(9):1208-1212)All Cited References & Full Image Credits are Listed on the Back Side of this Chart is an educational reference to increase awareness about Autoinflammatory document is not intended to replace professional medical care, diag-nosis and/or treatment by a qualified specialist. It is to be used only for non-commercial, educational purposes. 2013 The NOMID Alliance. Main authors: Karen Durrant RN, BSN President of The NOMID Alliance, & Dr Juan Ignacio Ar stegui MD Immunologist at the CDB Hospital Cl nic in Barcelona, Spain & Director of La Unidad de Enfermedades Autoinflamatorias ( )Acknowledgements: A special thanks to the many medical doctors who have helped to make voluntary suggestions in regards to this reference Chart : Dr Juan Ignacio Ar stegui, Dr Hal Hoffman, Dr Raphaela Goldbach-Mansky, Dr Anna Simon, Dr Polly Ferguson, Dr Rebecca Marsh, Dr Daniel Kastner, Dr Luca Cantarini, Dr V ronique Hentgen, Dr Nico M.

3 Wulffraat, Dr Kieron Leslie & Dr Lori Broderick. Thank you Nathan Durrant for donating your graphic design services. Our deepest thanks to The NOMID Alliance Board of Directors, & to all the patients & families who have supplied images for this Chart , & support for The NOMID Alliance. You are our greatest inspiration and strength! A special 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 this 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 R f rence des Maladies Auto-inflammatoires (CeR MAI) & Le Club Rhumatismes et Inflamations; Der-matology Online Atlas.

4 (DermIS Dermatology Information System), the Pediatric Rheumatology European Society (PReS), PRINTO, the EUROFEVER Project, EULAR, CARRA & the many other research centers and doctors around the world. Thanks to The American College of Rheumatology (ACR) for their efforts & for our non-profit rate booth at ACR 2013 Annual : 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. Novartis Pharmaceuticals Canada Inc. provided The NOMID Alliance with an unrestricted grant in 2012 to help with the initial development & printing costs for this Chart . A generous unrestricted grant from Swedish Orphan Biovitrum AB (Sobi) in 2013 is currently supporting many projects, including: the printing of this Chart for the ACR meeting, patient picnics in 2014, & an educational grant for our injection tips guide for families, and some other projects that will be developed in 2014.

5 The NOMID Alliance has received a number of unrestricted grants at various times from Regeneron, Novartis & Sobi for grant-specific projects. Karen Durrant has received reimbursement 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 NOMID Alliance is a 501(c)(3) non-profit organization dedicated to improving aware- ness, care and treatment for patients with CAPS or other Autoinflammatory Box 590354 San Francisco, CA 94159 ACE: Angiotensin-converting enzyme (lab test)ADA2: Adenosine deaminase 2 ANCA+ Vasculitis: Granulomatosis w/polyangiitis (GPA); Wegener sARDS: Acute Respiratory Distress SyndromeCD14+ monocytes: Cluster of differentiation 14 positive monocytesCD19: B-lymphocyte antigen CD19-aka Cluster of Differentiation 19CD25: Soluble interleukin-2-receptorCNS: Central Nervous System (involving the brain, spinal cord)CRP: C-reactive protein (lab test); DIC: Disseminated intravascular coagulationESR: Erythrocyte sedimentation rate (lab test).

6 Westergren ESRGI: Gastrointestinal (organs in the abdomen)HSP: Henoch Sch nlein purpura, anaphylactoid purpuraICP: Intracranial pressureIDDM: Insulin-Dependent Diabetes MellitusLFTs: Liver function tests (lab test): AST, ALT, GGT, ALK Phos, BilirubinNK cells: Natural killer cellsPMNs: Polymorphonuclear leukocytes (on lab tests w/ WBC count)pt.: abbreviation for the word patient PTT: Partial thromboplastin time (lab test)SAA: Serum amyloid A protein (lab test)TSH: Thyroid-stimulating hormone (lab test); thyrotropinw/: abbreviation for the word with WBC: White Blood Count (lab test)List of abbreviations:Beh ets DiseaseTumour Necrosis Factor (TNF)- Associated Periodic Sydrome aka Familial Hiber-nian Fever* SchnitzlerSyndromePeriodic Fever, Aphthous Stoma-titis, Pharyngitis, & Cervical Ad-e n i t i s ( P F A PA ) aka Marshall SyndromeChronic Atypical Neutrophilic Dermatosis w/ Lipodystrophy & Elevated Temper-ature aka Nakajo-Nishimura SyndromeAdult-OnsetStills Disease aka Adult Still s, Wissler-Fanconi SyndromeFamilial Psoriasis(PSORS2) akaCARD14-MediatedPustular PsoriasisPyogenic Sterile Arthritis,Pyoderma Gangrenosum, & Acne SyndromeFamilial Mediterranean Fever*Familial ColdAutoinflammatorySyndrome*Muckle-Well sSyndrome*Neonatal-OnsetMultisystemAutoi nflammatoryDisease aka Chronic Infantile Neurological Cutaneous Articular Syndrome (CINCA)*Deficiency ofInterleukin-1 (IL-1 ) Receptor Antagonist (DIRA)

7 Aka Osteomyelitis, Sterile Multifocal w/Periostitis PustulosisMajeed Syndrome aka Chronic Recur-rent Multifocal Osteo-myelitis, Congenital Dyserythropoietic Anemia, & Neutro-philic DermatosisHyperimmuno-globulinemia D with PeriodicFever Syndrome (HIDS)*MevalonateAciduria (MA)(Mevalonate Kinase Deficiencies, such as HIDS & MA are also referred to as MKD)Chronic Recurrent MultifocalOsteomyelitis aka Synovitis, Acne, Pustulosis, Hyperosto-sis, Osteitis SyndromeJuvenile Systemic Granulomatosis aka Blau syndrome, Pediatric Granuloma-tous Arthritis (PGA), Early Onset Sarcoido-sis, or Jabs SyndromeNLRP12-Associat-ed Periodic Fever Syndrome aka Familal Cold Autoin-flammatory Syndrome 2, or Guadaloupe Periodic FeverSystemic-Onset Juvenile IdiopathicArthritis aka Still s, Systemic Juvenile Idiopathic Arthritis NLRP3 Autosomal mutations,few familial present in all all races, but many are of European all races, but many are of European mutations,some familial familial groups, some spontaneous w/increased symptoms & fever during Chronic inflammation noted between flares.

8 1:1 million, or more. In USA 300+ diagnosed most cases are from large family ,51:1 million, maybe more. Some large family Frequency of CAPS in France is 1:360, frequency 1:1 million, mostly due to spontaneous genetic hours, or of fever & flares is often 1-3 hours after exposure to cold or cooling lasts 2-3 onset flares of fever & symptoms are often triggered by cold or cooling infancy. Rash, symptoms, & abnormal labs are often present at ,6 Infancy, but a few present w/symptoms later in childhood or induced urticaria-like rash w/increased neutrophils at the ec-crine Almost daily rash that increases rash w/increased neutrophils at the eccrine Most w/daily rash that increases Urticaria-like rash w/increased neutrophils at the eccrine coils. Rash increases have headaches, fatigue w/fever after cold if there are notable CNS affects at this have headaches, fatigue w/fever & to have many other CNS A few pts. have MWS/NOMID crossover of , fever, fatigue, chronic aseptic meningitis, & high CNS pressure (ICP).

9 Many with mental &/or cogni-tive impairments. Papille-dema is have increased sensorineural hearing loss, from ,6 Many have increased sensorineural hearing loss, starting in pts have mild hearing loss not cur-rently known if it s from CAPS (non-infectious) during (non-infectious) during flares,1 or corneal MWS/NOMID crossover pts. may have more eye , uveitis, iritis, conjunctivitis. Some w/retinal scarring, corneal haze or vision ,26 Some have clubbing of fingers. Some cases of pericardial effusions, have abdominal pain w/flares or other gastrointestinal , vomiting & abdominal pain w/flares, or w/high CNS pts. with enlarged liver and/or spleen, many have enlarged lymph pain, knee valgus or varus. Some w/frontal bossing, saddleback nose, contractures, <50% of patients knees have bony overgrowth. Short stature, growth delays failure to thrive, arthritis, & osteopenia ,26 Arthralgias, recurrent arthritis, stiffness & swelling with Arthralgias, stiffness & swelling with Not serum amy-loid (SAA).

10 Secondary amyloidosis in some ,9 Elevated SAA. >25 % w/secondary ,9 Elevated SAA. Second-ary amyloidosis in <2% ,6 High: ESR, CRP, SAA. Leukocytosis with : ESR, CRP, SAA. Leukocytosis,with high: ESR, CRP, SAA, anemia, granulocyte ,6 MEFVA utosomal cases are gene-dosage-dependent autosomal , Armenian, Arab,Sephardic Jew, Most common inherited periodic fever specific ethnic groups, the carrier frequency of MEFV vari-ants is up to 1:5 ,9 Recurrent fever & flares can occur weekly, or only a few times a , to under 20 years of age for the first erythema on the ankle foot be-low knee region lasts 2-3 days during flares of Acute aseptic meningitis is rare & can occur during flares, but is never Other neurological involve-ment is very rarely seen in not be-lieved to be caused by a FMF rare to have pleuritis, pain-ful respiration, peritonitis, pain, and/or constipation with spleen iscommon, some have enlarged lymph , oligoarthritis & clubbing are common.