Table I.
Clinical features, molecular basis, histologic and laboratory findings of autoinflammatory syndromes
| Disease | Skin and nail findings | Systemic manifestations | Length of fevers |
Histology | Gene/protein | Laboratory findings |
|---|---|---|---|---|---|---|
| CAPS (AD) | Urticaria-like eruptions | Fevers, distal arthralgia, neurologic symptoms, eye disease, amyloidosis | Daily | Perivascular, interstitial, or perieccrine neutrophilic infiltrate |
NLRP3/CIAS1 Cryopyrin |
Leukocyte count (↑), CRP, ESR, and SAA (↑), creatinine (↑), IL-1ß (↑) |
| PAPA syndrome (AD) | Pyoderma gangrenosum, acne | Pyogenic arthritis | Variable | – |
PSTPIP1 PSTPIP1 |
CRP and ESR (↑), gammaglobulin (↓); IL-1ß and TNF-alfa (↑); joint culture (often –) |
| Blau syndrome (AD) | Densely populated, erythematous papular eruptions | Fevers, polyarthritis (±camptodactyly), eye disorders;granulomatous kidney, liver, lung, and CNS disease | Variable | Noncaseating granulomata | CARD15 CARD15 | ESR (↑), ACE (↑), IgA and IgG (↑); IL-1ß (↑) |
| TRAPS (AD) | Erysipelas-like macules and patches overlying myalgia | Fevers, focal myalgia, abdominal pain, conjunctivitis, periorbital edema, LAD | 7-21 d | Perivascular and interstitial lymphocytic infiltrate |
TNFRSF1A TNF receptor |
CRP and ESR (↑), haptoglobin, fibrinogen, and ferritin (↑) |
| HIDS (AR) | Intermittent erythematous macules or morbilliform papular eruptions | Fevers, arthralgia, severe abdominal pain, LAD, splenomegaly, amyloidosis | 1-2 d | Perivascular IgD and C3 complex deposits |
MVK Mevalonate kinase |
IgD and IgA (↑), IL-1ß and TNF-alfa (↑);urine mevalonic acid (↑) |
| FMF syndrome (AR) | Acral erysipelas-like erythema and purpuric lesions | Periodic fevers, synovitis, serositis, HSP, polyarteritis nodosa, protracted febrile myalgia, amyloidosis | 1-3 d | Perivascular lymphocytes, neutrophils, and histiocytes |
MEFV Pyrin |
CRP and ESR (↑), SAA (↑), creatinine (↑); IL-1ß and TNF-alfa (↑) |
| DIRA syndrome (likely AR) | Generalized pustulosis, nail changes (±) | Periostitis, osteomyelitis, hepatosplenomegaly, radiographic skeletal abnormalities | Variable | Neutrophilic infiltrate with hyperkeratosis, follicular pustules |
IL1RN IL-1 antagonist |
IL-1ß (↑);bone-tissue culture (often –) |
| CANDLE syndrome (likely AR) | Annular violaceous plaques | Fevers, edematous eyelids, progressive facial lipodystrophy, arthralgia, and delayed physical development | Daily | Perivascular and interstitial neutrophilic infiltrate |
PSMB8 PSMB8 |
ESR and hepatic transaminases (↑) |
| SAPHO syndrome | Palmoplantar pustulosis (±psoriasis), severe acne | Chronic synchondrosis inflammation, osteosclerosis, hypertrophic osteitis, and synovitis | Variable | – | – | CRP and ESR (↑); IL-1ß and TNF-alfa (↑); skin culture for Staphylococcus aureus and Propionibacterium acnes (often +) |
| Schnitzler syndrome | Nonpruritic urticarial plaques | Fevers, arthritis, hyperostosis, osteosclerosis, IgM gammopathy | – | Perivascular lymphocytes, histiocytes, and neutrophils | – | CRP and ESR (↑); IL-1ß, IL-6, and IL-18 (↑) |
| SOJIA | Morbilliform erythematous macules and papules | Spiking fevers, polyarticular arthritis | Daily | Perivascular and interstitial neutrophils and lymphocytes | – | IL-1ß, IL-6, and IL-18 (↑) |
ACE, Angiotensin-converting enzyme; AD, autosomal dominant; AR, autosomal recessive; CANDLE, chronic atypical neutrophilic dermatitis with lipodystrophy and elevated temperature; CAPS, cryopyrin-associated periodic syndrome; CARD, caspase-recruiting domain; CARD15, caspase-recruiting domain 15; CIAS1, cold-induced autoinflammatory syndrome 1; CNS, central nervous system; CRP, C-reactive protein; DIRA, deficiency of interleukin-1 receptor antagonist; ESR, erythrocyte sedimentation rate; FMF, familial Mediterranean fever; HIDS, hyper-IgD syndrome; HSP, Henoch-Schönlein purpura; IL, interleukin; IL1RN, interleukin 1 receptor antagonist; LAD, lymphadenopathy; MEFV, mediterrean fever; MVK, mevalonate kinase; NLRP, nucleotide-binding domain leucine-rich repeat-containing protein; NLRP3, nucleotide-binding domain leucine-rich repeat-containing protein 3; PAPA, pyogenic arthritis, pyoderma gangrenosum, and acne; PSMB8, proteasome subunit ß type 8; PSTPIP1, proline-serine-threonine phosphatase interacting protein 1; SAA, serum amyloid A; SAPHO, synovitis, acne, pustulosis, hyperostosis, and osteitis; SOJIA, systemic-onset juvenile idiopathic arthritis; TNF, tumor necrosis factor; TNFRSF1A, tumor necrosis factor receptor superfamily, member 1A; TRAPS, tumor necrosis factor receptor—associated periodic syndrome.