Table 1.

Brief summary of the hereditary monogenic autoinflammatory diseases.

	Gene Locus	Protein	Inheritance	Main Manifestations and Complications	Available Treatments
FMF	MEFV 16p13.3	PYRIN or marenostrin	AR	serositis, limb pain or transient arthritis, erysipelas-like eruption on the legs, nonspecific skin manifestations (like urticaria, angioedema, erythema nodosum, vasculitis), risk of amyloidosis	Colchicine, canakinumab, anakinra
TRAPS	TNFRSF1A 12p13	TNFRSF1A, TNF receptor	AD	severe migrating muscle pain, arthralgia or arthritis, serositis, painful orbital edema, painful conjunctivitis, risk of amyloidosis	Canakinumab, anakinra, corticosteroids
FCAS	NLRP3 1q44	CRYOPYRIN	AD	cold-induced urticaria-like rashes, conjunctivitis, arthralgia	Anakinra, rilonacept, canakinumab
MWS				cold-induced urticaria-like rash, conjunctivitis, episcleritis, arthralgia, neurosensorial deafness, risk of amyloidosis
CINCA				migrating non-itchy urticaria-like rash, uveitis, papilledema, deforming arthritis involving large joints, aseptic chronic meningopathy, retinal dystrophy, neurosensorial deafness, risk of amyloidosis
MKD	MVK 12q24	MEVALONATE KINASE	AR	fatigue, painful generalized lymph node enlargement, vomiting, diarrhea, abdominal pain, arthralgia, skin rashes of varying severity, oral and/or genital aphthosis, splenomegaly during flares	Anti-inflammatory drugs, corticosteroids, anakinra ‘on demand’, canakinumab
PAPA	PSTPIP1 15q24–25	PSTPIP1 (proline-serine- threonine phosphatase interacting protein 1)	AD	sterile pyogenic arthritis, pyoderma gangrenosum, severe acne, skin abscesses, recurrent non-healing sterile ulcers	Corticosteroids, infliximab, anakinra, immunosuppressive agents
MS	LPIN2 18p11.31	LIPIN2 (phosphatidate phosphatase)	AR	recurrent multifocal osteomyelitis, neutrophilic dermatosis, dyserythropoietic anemia	Corticosteroids, bisphosphonates, TNF-α inhibitors, IL-1 antagonists (anakinra)
DIRA	IL1RN 2q14.1	IL1RN (interleukin-1 receptor antagonist)	AR	sterile multifocal osteomyelitis starting in the neonatal period, skin pustulosis, osteitis	Anakinra
BS	NOD2 (CARD15) 16q12.1–13	NOD2 (nucleotide binding oligomerization domain containing 2)	AD	non-erosive granulomatous polyarthritis (‘boggy synovitis’ with painless effusion and cyst-like swelling of joints), granulomatous panuveitis, skin granulomatous rash	Corticosteroids, TNF-α inhibitors (infliximab), IL-1 antagonists, JAK inhibitors (tofacitinib)
DITRA	IL36RN 2q14.1	IL36RN (interleukin-36 receptor antagonist)	AR	severe pustular psoriasis (generalized or limited to the distal part of limbs)	TNF-α inhibitors (adalimumab), IL-12/23 antagonists, IL-17 antagonists
CAMPS	CARD14 17q25.3	CARD14 (caspase recruitment domain- containing protein 14)	AD	psoriasis in a wide range of phenotypes	Methotrexate, corticosteroids, cyclosporine, phototherapy, acitretin, vitamin D analogs, TNF-α inhibitors, IL-12/23 antagonists, IL-17 antagonists
ORAS	OTULIN 5p15.2	OTULIN (deubiquitinase)	AR	fever starting in the neonatal period, neutrophilic dermatosis associated with panniculitis, growth retardation	TNF-α inhibitors
HA20	TNFAIP3 6q23.3	TNFAIP3 (tumor necrosis factor alpha-induced protein 3, A20)	AD	recurrent mucosal ulcerations of the oral cavity, gastrointestinal tube and urogenital tract, skin rashes, polyarthritis, uveitis, vasculitides, recurrent fevers, association with different autoimmune disorders (systemic lupus erythematosus, psoriatic arthritis, juvenile idiopathic arthritis, autoimmune hepatitis and Hashimoto thyroiditis)	TNF-α inhibitors, colchicine
FCAS2	NLRP12 19q13.42	NLRP12 (nucleotide- binding oligomerization domain, leucine rich repeat and pyrin domain containing 12)	AD	cold-induced rashes, joint pain, abdominal pain, sensorineural deafness, headache	Anakinra, TNF-α inhibitors, IL-6 antagonists (tocilizumab)
PRAAS	PSMB8	PSMB8 (proteasome 20s subunit beta 8)	AR	chronic atypical neutrophilic dermatosis, lipodystrophy, erythema nodosum-like panniculitis, abnormal growth of lips, muscular weakness and atrophy, severe joint contractures, basal ganglia calcifications, ear and nose chondritis, aseptic meningitis, conjunctivitis, hepatosplenomegaly, lymph node enlargement, arthralgia	Corticosteroids, immunosuppressive agents, anakinra, IL-6 antagonists (tocilizumab), TNF-α inhibitors, dapsone, JAK inhibitors (baricitinib)
SAVI	STING1 (TMEM173) 5q31.2	STING1 (stimulator of interferon genes protein 1)	AD	vasculopathy causing severe skin lesions on face, ears, nose and digits, resulting in ulcerations, necrosis or amputations, chronic interstitial lung disease	JAK inhibitors (ruxolitinib)
AGS	TREX1, RNASEH2B, RNASEH2C, RNASEH2A, SAMHD1, ADAR, IFIH1 3p21.31, 13q14.3, 11q13.1, 19p13.13, 20q11.23, 1q21.3, 2q24.2	Enzymes involved in the duplication, repair and recombination of nucleic acids	AR (AD for IFIH1)	leukoencephalopathy (mimicking transplacental infections), calcifications in cerebral and basal ganglia, dystonia, microcephaly, cognitive impairment, abnormal eye movements, glaucoma, livedo reticularis, digital chilblain lesions on hands and feet, hepatosplenomegaly, jaundice, silent positivity of autoantibodies	No cure is available, corticosteroids and intravenous immunoglobulin may control systemic and organ inflammation

FMF: familial Mediterranean fever; TRAPS: tumor necrosis factor receptor-associated periodic syndrome (autosomal dominant familial periodic fever); FCAS: familial cold-induced autoinflammatory syndrome; MWS: Muckle-Wells syndrome; CINCA s.: chronic infantile neurologic cutaneous articular syndrome; MKD: mevalonate kinase deficiency (hyper-IgD syndrome); PAPA s.: pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome; MS: Majeed syndrome; DIRA: deficiency of IL-1 receptor antagonist; BS: Blau syndrome; DITRA: deficiency of the interleukin-36 receptor antagonist; CAMPS: CARD14-mediated psoriasis; HA20: haploinsufficiency of A20; ORAS: OTULIN-related autoinflammatory syndrome; FCAS2: familial cold autoinflammatory syndrome 2 (NLRP12-associated autoinflammatory disorder); PRAAS: proteasome-associated autoinflammatory syndrome; SAVI: STING-associated vasculopathy with onset in infancy; AGS: Aicardi-Goutières syndrome. AR: autosomic recessive; AD: autosomic dominant; TNF: tumor necrosis factor; IL-1: interleukin-1; JAK: Janus kinase.