Untangling the Web of Systemic Autoinflammatory Diseases

Table 1

Brief summary of clinical features of systemic autoinflammatory diseases.

Disease	Gene locus	Protein	Inheritance	Clinical features	Treatment
FMF	MEFV; 16p13.3	Pyrin (marenostrin)	AR	Fever, serositis, arthralgias or arthritides, erysipelas-like eruption on the legs, and systemic amyloidosis in untreated or noncompliant patients	Colchicine, anakinra, and canakinumab
MKD	MVK; 12q24	Mevalonate kinase	AR	Fever, polymorphous rash, arthralgias, abdominal pain, diarrhea, lymph node enlargement, splenomegaly, and aphthosis	NSAIDs, corticosteroids, anakinra, and anti-TNF-α agents
TRAPS	TNFRSF1A; 12p13	Tumor necrosis factor receptor 1	AD	Fever, migratory muscle and joint involvement, conjunctivitis, periorbital edema, arthralgias or arthritis, serosal involvement, corticosteroid responsiveness of inflammatory attacks, and risk of amyloidosis	Corticosteroids, etanercept, and anakinra
FCAS	NLRP3; 1q44	Cryopyrin	AD	Fever, cold-induced urticaria-like rash, conjunctivitis, and arthralgias	Anakinra, rilonacept, and canakinumab
MWS				Fever, urticaria-like rash, conjunctivitis and episcleritis, arthralgias, neurosensorial deafness, and amyloidosis
CINCAs				Subcontinuous fever, early-onset urticaria-like rash, clubbing, corneal clouding, anterior or posterior uveitis, papilledema, retinopathy with scarring, optic nerve atrophy, aseptic chronic meningitis, increased intracranial pressure, inner ear inflammation with neurosensorial deafness, deforming osteoarthritis involving large joints, bony overgrowth, joint contractures, severe growth retardation with facial dysmorphic features (frontal bossing and flattening of the nasal bridge), and amyloidosis
NLRP12-AD	NLRP12; 19q13	Monarch-1	AD	Fever, arthralgia, cold-induced urticaria-like rash, abdominal complaint, and risk of sensorineural deafness	Antihistamines, NSAIDs, anakinra, anti-TNF-α agents, and IL-6 receptor antagonists
BLAUs	NOD2 (CARD15); 16q12.1-13	NOD2	AD	Granulomatous dermatitis with ichthyosis-like changes, symmetrical granulomatous polyarthritis, recurrent granulomatous panuveitis, risk of cranial neuropathies, and intermittent fever	Corticosteroids, immunosuppressive agents, anti-TNF-α; agents, and thalidomide
PHIDs	SLC29A3; 10q22	hENT3	AR	Fever, pigmented skin lesions, hypertrichosis, insulin-dependent diabetes mellitus, pancreatic insufficiency, cardiomyopathy, lipodystrophy, scleroderma-like lesions, short stature, and delayed puberty	Etoposide?
NNS	PSMB8; 6p21	Inducible; subunit β of the proteasome	AR	Fever, long clubbed fingers and toes with joint contractures, lipomuscular atrophy, pernio-like rash in hands and feet, heliotrope rash on the eyelids, nodular skin lesions, basal ganglia calcification, and hepatosplenomegaly	Corticosteroids, anti-TNF-α agents, and anti-IL-1 agents
CANDLEs				Recurrent fever, arthralgia, purplish skin lesions, abnormal growth of lips, lipodystrophy, hypertrichosis, acanthosis nigricans, alopecia areata, nodular episcleritis, conjunctivitis, chondritis of the nose and ear, aseptic meningitis, and basal ganglia calcification	Corticosteroids, anti-TNF-α agents, IL-6 receptor; antagonists, and baricitinib
PAPAs	PSTPIP1; 15q24-q25.1	CD2BP1	AD	Pauciarticular pyogenic arthritis, osteocartilaginous erosions of joints, cystic acne, ulcerative lesions of lower limb extremities, and pyogenic abscesses	Corticosteroids, etancercept, infliximab, and anakinra
DIRA	IL1RN; 2q14.2	IL-1 receptor antagonist	AR	Neonatal multifocal osteomyelitis, periostitis with osteolytic lesions, pustulous, and ichthyosis skin rash	Anakinra and corticosteroids
DITRA	IL36R; 2q14	IL-36 receptor antagonist	AR	Fever, pustulous skin lesions on the palms and soles, glossitis, arthritis, severe bone pain, and asthenia	Corticosteroids, methotrexate, cyclosporine, anakinra, and acitretin
MAJEEDs	LPIN2; 18p11.31	Lipin-2	AR	Recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, neutrophilic dermatosis with palmoplantar pustulosis, or pyoderma gangrenosum	NSAIDs, corticosteroids, anakinra, and canakinumab
CRMO	Unknown, presumably; polygenetic trait		Currently; unknown	Osteomyelitis, bone pain with localized osteolysis, potential association with Sweet’s syndrome, acne, or inflammatory bowel disease, recurrent fever	NSAIDs, corticosteroids, bisphosphonates (pamidronate, neridronate), and anti-TNF-α agents (infliximab)

AD: autosomal dominant; AR: autosomal recessive; BLAUs: Blau syndrome; CANDLEs: chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature; CINCAs: chronic infantile neurologic cutaneous articular syndrome; CRMO: chronic recurrent multifocal osteomyelitis; DIRA: deficiency of the interleukin-1-receptor antagonist; DITRA: deficiency of the IL-36 receptor antagonist; FCAS: familial cold autoinflammatory syndrome; FMF: familial Mediterranean fever; MAJEEDs: Majeed syndrome; MKD: mevalonate kinase deficiency syndrome; MWS: Muckle-Wells syndrome; NLRP12-AD: NLRP12-associated autoinflammatory disorder; NNS: Nakajo-Nishimura syndrome; NSAIDs: nonsteroidal anti-inflammatory drugs; PAPAs: pyogenic arthritis, pyoderma gangrenosum, and acne syndrome; PHIDs: pigmentary hypertrichosis and nonautoimmune insulin-dependent diabetes mellitus syndrome; TRAPS: tumor necrosis factor receptor-associated periodic syndrome.