Table 1.

Monogenic autoinflammatory syndromes

General pathway	Disease	Gene	Affected protein	Mode of inheritance	Age of onset	Key clinical features	Treatment
Inflammasomopathies	FMF	MEFV	Pyrin	AR/AD	0–20 years	Peritonitis, joint attacks and joint pain	Colchicine/anti-IL-1
	PAAND	MEFV	Pyrin	AD	0–10 years	Neutrophilic dermatosis (pyoderma gangrenosum) arthralgia, myalgia	Anti-IL-1/anti-TNF
	PAPA	PSTPIP1	CD2 binding protein-1	AD	1–16 years	Juvenile-onset arthritis, painful ulcers and acne	Prednisone/anti-IL-1, anti-TNF
	MKD	MVK	Mevalonate kinase	AR	Variablea	Lymphadenopathy, abdominal pain, joint pain, diarrhoea, skin rashes and headache	NSAIDs/prednisone/anti-IL-1, anti-TNF
	NLRP3-AID (spectrum) CINCA/NOMID, MWS, FCAS	NLRP3	NLRP3	ADb	Variablea	Conjunctivitis, general malaise, headaches, rash, joint pain	Anti-IL-1
	NLRP12-AIDc	NLRP12	Monarch-1 protein	AD	Infancy	Skin rash, lymphadenopathy, aphthous ulcers, abdominal complaint	Anti-IL-1/corticosteroids
	NLRC4-AID	NLRC4	NLRC4	AD	Infancy	Infantile enterocolitis Macrophage activation syndrome	Anti-IL-1/anti-IL-18
	NLRP1-AIDc	NLRP1	NLRP1	AD	6 months–10 years	Dyskeratosis, arthritis	Acitretin, anti-IL-1
Interferonopathies	Aicardi–Goutières syndrome	TREX1 RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1	Exonuclease subunits of the RNase H2 endonuclease complex, control of dNTP pool	AD/AR	Infancy–childhood	Encephalopathy, hepatosplenomegaly, skin lesions	Symptomatic treatment JAK inhibition Reverse transcriptase inhibitors
	Proteasome-associated autoinflammatory syndrome (PRAAS), CANDLE	PSMB3, PSMB4, PSMB8, PSMB9, POMP	Proteasome	AR	Infancy	Skin eruptions, progressive lipodystrophy, hepatosplenomegaly, myositis,	Glucocorticoids JAK inhibition
	SAVI	TMEM173	Stimulator of interferon genes (STING)	AD	Infancy-childhood	Vasculopathy, skin lesions (leading to ulcers and necrosis), Raynaud phenomenon	JAK inhibition
Relopathies	A20 haploinsufficiency	TNFAIP3	NF-κB regulatory protein, A20	ADa (some cases unclear)	Variable	Oral, gastrointestinal and genital ulcers; arthralgia	Colchicine, systemic corticosteroids, anti-IL-1, anti-IL-6, anti-TNF
	Biallelic RIPK1 mutations	RIPK1	Receptor-interacting serine/threonine kinase 1	N/A	Infancy	Early-onset inflammatory bowel disease, and progressive polyarthritis	HSCT successful in one patient
	HOIL-1/HOIP deficiency	HOIL-1, HOIP	HOIP, HOIL-1 and SHARPIN (components of LUBAC)	AR	Infancy	Amylopectinosis, increased susceptibility to viral and bacterial infections	HSCT
	ORAS	OTULIN	Otulin (deubiquitinator protease)	AR	Infancy	Panniculitis, diarrhoea, swollen joints	Anti-TNF
	RELA (p65) haploinsufficiency	P65	REL-associated protein	AD	Variable	Abdominal pain, mucocutaneous ulceration vomiting, leukocytosis	Anti-TNF
Others	DADA2	CECR1	Adenosine deaminase 2	AR	Variable	Mottled rash (livedo reticularis) anaemia, joint pain, fatigue	Anti-TNF, bone marrow transplantation
	DIRAd	IL1RN	IL-1 Receptor antagonist	AR	Infancy	Painful joint swelling, pustular rash, hepatosplenomegaly	IL-1 blockade
	DITRA	IL36RN	IL-36 Receptor antagonist	AR	Infancy	Pustular psoriasis, asthenia	IL-1 blockade, anti-TNF
	TRAPSc	TNFRSF1A	TNF	AD	Variable	Skin rash, abdominal pain, myalgia	Corticosteroids, anti-IL-1/ anti-TNF
	NOD2- associated granulomatous disease, Blau syndromec	NOD2	NOD2 inflammasome	ADe	Infancy-childhood	Granulomatous dermatitis, arthritis, uveitis	Anti-TNF

Aside from apparent high fever, other key clinical features are stated.

Key references used to construct this table [38, 47, 72–77].

^aAge of onset depends on disease severity.

^bReports of sporadic cases as well.

^cThese diseases are included for informational purposes, but not discussed in the review. Readers are encouraged to research these pathways in literature.

^dFever is not a typical feature in this condition. AD: autosomal dominant; AID: associated inflammatory disease; AR: autosomal recessive; CAMPS: CARD14-mediated pustular psoriasis; CANDLE: chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome; CINCA: chronic infantile neurological, cutaneous and articular syndrome; DADA2: deficiency of adenosine deaminase 2; DIRA: deficiency of interleukin-1 receptor antagonist; DITRA: deficiency of the IL-36 receptor antagonist; FCAS2: familial cold autoinflammatory syndrome 2; HOIL-1L: haem-oxidized IRP2 ubiquitin ligase 1L; HOIP: HOIL-1 interacting protein; HSCT: haematopoietic stem cell transplantation; LUBAC: linear ubiquitin chain assembly complex; MKD: mevalonate kinase deficiency; MWS: Muckle–Wells syndrome; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; NOD2: Nucleotide-binding oligomerization domain-containing protein 2; NOMID: neonatal onset multisystem inflammatory disease; ORAS: ovarian tumor (OTU) deubiquitinase with linear linkage specificity (OTULIN)-related autoinflammatory syndrome; PAAND: pyrin-associated autoinflammation with neutrophilic dermatosis; PAPA: pyogenic arthritis, pyoderma gangrenosum and acne syndrome; RELA (p65): Transcription factor p65; SAVI: sting-associated vasculopathy with onset in infancy; SHARPIN: SHANK-associated RH-domain-interacting protein; TRAPS: TNF-associated periodic fever syndrome.