Comparison Chart

Click on a disease to learn more, and to see larger images. Use Symptom Search to look for certain disease features.

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
Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) – aka Marshall Syndrome Idiopathic Currently unknown. No genetic testing available. Currently unknown. Affects all races. [40] Unknown. PFAPA is the most common non-infectious recurrent fever disorder. [40] Periodic fevers and symptoms lasting 3-6 days, recurring every 21-28 days. Extremely predictable frequency of days between the onset flares in most cases. Patients are symptom-free between flares. No specific triggers have been identified–flares come at regular intervals, often monthly. [40] If there are any persistent symptoms between flares, evaluation for autoinflammatory periodic fever syndromes is essential. Early childhood, usually between 2-5 years of age. A few adult-onset cases are documented. Most teens outgrow it. [40] Aphthous ulcers (stomatitis), and pharyngitis with exudate, (but no infection) is a classic finding. [40] [41] Skin rashes are not typical, or a part of the PFAPA diagnostic criteria-if rashes occur with flares, or are persistent between flares, other autoinflammatory diseases should be considered. High fevers for 3-6 days, with chills and malaise. Some patients have headaches with flares. Other neurological symptoms are not noted. [41] Not noted. [40] [41] Not noted. [40] [41] Flares of fevers, stomatitis and pharyngitis are not associated with respiratory illness. [40] [41] Abdominal pain, and diarrhea are often present with flares. [40] [41] Cervical adenopathy or lymphadenopathy during flares. [40] [41] Arthralgias, fatigue and malaise. No permanent joint or bone issues noted, and patients are symptom-free between PFAPA flares. [40] [41] Not noted. [40] [41] Not noted. [40] [41] High: ESR, CRP, WBC during flares only. All normal labs when not flaring, or between flares. [40] [41] IgD may be elevated in patients with PFAPA (and these patients were negative for MVK mutations). [126] PFAPA symptoms overlaps with a number of other autoinflammatory periodic fever syndromes, so genetic testing and attention to clinical findings may be helpful.
Mevalonate Aciduria (MA), Mevalonate Kinase Deficiency-severe Mevalonate Kinase Deficiency (MKD) MVK Autosomal recessive. Mostly of Dutch descent, or Northern European. [1] Unknown, but very rare. <100 known patients worldwide. [11] 4-5 days. Recurrent flares with fevers every 2-3 weeks. Patients have chronic inflammation noted between flares. [11] Most present with symptoms at birth, or in early infancy. Most have facial features noted at birth. [11] Diffuse maculopapular or morbilliform rash. Some with petechiae or purpura present. A few with apthous ulcers. [1], [9], [11] Fevers with flares. Microcephaly, dolichocephaly, intellectual disability, cognitive and/or developmental delays, cerebellar ataxia, cerebellar atrophy and seizures (epilepsy) often develop over time. [11] Patients with Mevalonate Kinase Deficiencies can have flares triggered by vaccines. Uncommon–not believed to be caused by MA. [1] [9] [11] Uveitis, central cataracts, blue sclerae and tapetoretinal degeneration are often present, even in less severe cases. [11] Rare. [1] [11] Hepatomegaly, splenomegaly or hepatosplenomegaly. Cholestatic liver disease. Abdominal pain, vomiting and diarrhea with flares. [1] [9] [11] One case with hepatic fibrosis. [135] Splenomegaly, and/or lymphadenopathy are common. [1], [11] Congenital defects are often noted: microcephaly, dolichocephaly, wide irregular fontanels, low set and posteriorly rotated ears, downslanted palpebral fissures. Hypotonia, myopathy, arthralgia, arthritis and failure to thrive are common. [11] Not noted. [11] Not noted-unknown. [9] [11] Anemia, leukocytosis, thrombocytopenia. High: ESR, CRP, SAA, CK, IgD, IgA, IgE; chronically high Mevalonate aciduria. [1] [11]
Mevalonate Kinase Deficiency-mild/moderate, Hyperimmunoglobulinemia D with Periodic Fever Syndrome Mevalonate Kinase Deficiency (MKD) MVK Autosomal recessive. Some cases with only one mutation found. [33] Mostly of Dutch descent, or Northern European. [1] Unknown, but very rare. >200-300 known patients worldwide, (>300, when suspected cases are also included.) [12] 3-7 days duration. Recurrent bouts of fever and flares every 2-12 weeks. [1] [9] Some flares occur after vaccines. [9] >90% present with symptoms in infancy. [9] Diffuse maculopapular rash. Polymorphous rashes. Some with petechiae or purpura present. [1], [9] 50% with apthous ulcers or genital ulcers. [130] Porokeratosis of Mibelli in one patient, and disseminated superficial actinic porokeratosis (DSAP) in a few cases of patients of Asian ancestry. [136] Headaches and fevers with flares of symptoms are common. [1] [9] More severe neurological symptoms are rarely present in HIDS. [9] Uncommon – not believed to be caused by HIDS. [1] [9] Uncommon. [9] Some with conjunctivitis. [134] and there are a few patients with retinitis pigmentosa (RP). [136] Rare. [1] Some patients have developed severe respiratory infections. Higher risk for issues with S. pneumoniae infections. [78] Extreme pain, vomiting and diarrhea with flares. [1], [9] A few cases with colitis, including early-onset, and sometimes severe colitis in the neonatal period, with bloody diarrhea. [136]. Some with hepatomegaly, splenomegaly, hepatosplenomegaly, or other gastrointestinal issues. [78] Cervical lymphadenopathy with flares. [1] A few with splenomegaly. [78] A few patients have had macrophage activation syndrome (MAS.) [136] Arthralgias are common, symmetric polyarthritis is frequently noted. [1] Cutaneous vasculitis is common. Henoch-Schönlein purpura (HSP) is rare. [1] <5-10% – uncommon. [9] High: ESR, CRP, SAA with flares. Mevalonate aciduria noted during flares. [1] High IgD with IgA in 80% patients. IgD may be normal in infants and young children with HIDS. Note that there are other conditions where IgD may sometimes be elevated, (see also FMF, TRAPS, PFAPA on our chart) so this is not considered the most accurate diagnostic lab for MVK diseases.
Tumor Necrosis Factor (TNF) - Associated Periodic Syndrome (aka Familial Hibernian Fever) TNF-associated Autoinflammatory Diseases, Protein Folding TNFRSF1A Autosomal dominant. Spontaneous mutations, with some familial groups. [1] Affects all races. Second most common inherited SAID (after FMF). [1] Unknown. TRAPS affects 0.01:10,000 people in the European Union. [51] >1000 patients worldwide. [52] Days to weeks. An average flare lasts around three weeks. [1] [9] Most first attacks occur by 3 years of age, and almost all begin by 20 years of age. A few have symptoms start later in life. [9] Migrating rash with deep pain under the areas with the rash. Severe pain follows the rash path from the trunk outwards to the limbs. [9] Fevers lasting >3 days at over 38°C with flares. Some have headaches with flares of symptoms. [1] [9] Uncommon–not believed to be caused by TRAPS. [1] Conjunctivitis, and periorbital edema during flares. [1] [9] Common, including pleurisy. [1] Abdominal pain, peritonitis, diarrhea, and constipation with flares. Splenomegaly. [1] Splenomegaly is common; some have lymphadeopathy. [1] Intermittent or chronic arthritis in the large joints with muscle pain and swelling is common. [1] Henoch-Schönlein purpura (HSP), lymphocytic vasculitis. [1] 10-20% occurrence. Higher risk with a cysteine mutation. [9] High: ESR, CRP, SAA. Polymorphonuclear neutrophils (PMNs), polyclonalgammopathy, leukocytosis. [1] Elevated serum IgD levels10% to 13% of patients with TRAPS (elevated in some with other autoinflammatory diseases too, such as HIDS, MA, FMF, PFAPA) [128]
Familial Mediterranean Fever Pyrin-associated Autoinflammatory Diseases (PAAD) MEFV Autosomal recessive in the majority of patients. Some cases have gene-dosage-dependent autosomal dominant inheritance. [10] Turk, Armenian, Arab, Sephardic Jew, Italian. [1] FMF is the most common inherited periodic fever syndrome. In specific ethnic groups, the carrier frequency of MEFV variants is up to 1:5 people. [1] 12-72 hours. [1] [9] Recurrent fever and flares can occur weekly, or only a few times a year. Infancy, to under 20 years of age for the onset of the first symptoms. [9] Adult-onset is uncommon, but can occur. Erysipeloid (erysipelas-like) erythema on the ankle–foot–below knee region that lasts 2-3 days during flares of symptoms. [1] Fevers. Acute aseptic meningitis is rare and can occur during flares, but is never chronic. [1] Other neurological involvement is very rarely seen in FMF. Uncommon–not believed to be caused by a FMF disorder. [1] Very rare to uncommon. [1] 45% have pleuritis, painful respiration with flares. Some with pericarditis. [1] Sterile peritonitis, pain, and/or constipation with flares. Splenomegaly. [1] Some cases of inflammation causing appendicitis symptoms, but the appendix is inflamed, not infected. Splenomegaly is common. Some have lymphadenopathy. [1] Mono or polyarthritis, oligoarthritis and clubbing are common. Ankle arthralgias are common. Severe arthritis of the hip or ankle is rare. [1] Henoch-Schönlein purpura (HSP), polyarteritis nodosa (PAN). [1] Secondary Amyloidosis is common. >50% in untreated patients; it depends on genotype. [9] High: ESR, CRP, SAA between flares. Fibrinogen, leukocytosis present with flares. [1] M694V and some with V726A mutations have higher risk for elevated IgD, and higher risk of more notable FMF symptoms, especially arthritis. [127] Elevated serum IgD levels 10% to 13% of patients with FMF (and TRAPS) [128]

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