Fever syndromes, hereditary, periodic (overview)A68.9
Synonym(s)
DefinitionThis section has been translated automatically.
ClassificationThis section has been translated automatically.
Clinic and genetics now allow a more precise differentiation. A distinction is made according to inheritance:
- Sporadically inherited:
- Autosomal recessive inherited clinical pictures:
- Familial Mediterranean fever (Familial Mediterranean fever/FMF)
- Hyper-IgD syndrome (HIDS).
- Autosomal-dominantly inherited diseases:
- Tumor necrosis factor receptor-associated periodic syndrome (TRAPS)
- Muckle-Wells syndrome (MWS )
- Familial cold urticaria (FCAS)
- Cryopyrin-associated periodic syndrome (CAPS): severe form of FCAS.
- Chronic infantile neurological cutaneous and articular syndrome (CINCA syndrome).
EtiopathogenesisThis section has been translated automatically.
Depending on the disease, the following genetic causes can be detected (diagnosis-determining):
- FMF: Mutations in the MEFV gene (Mediterranean fever gene; gene locus: 16p13.3).
- HIDS: Mutations in the MVK gene (mevalonate kinase gene; gene locus: 12q24)
- TRAPS: Mutations in the TNFRSF1A gene (TNF receptor superfamily 1A gene/gene locus: 12p13.2)
- Familial cold urticaria: mutations in the NLRP3 gene (alias CIAS1 gene/Cold-induced autoinflammatory syndrome gene/gene locus: 1q44).
- CAPS/cryopyrin-associated periodic syndrome (mutations in the NLRP3 gene/alias CIAS1 gene/Cold-induced autoinflammatory syndrome gene/gene locus: 1q44).
- Chronic infantile neurological cutaneous articular syndrome (mutations in the NLRP3 gene /alias CIAS1 gene/Cold-induced autoinflammatory syndrome gene/gene locus: 1q44)
The resulting functional changes in the proteins encoded by these genes, i.e. the pyrin in FMF, the mevalonate kinase in HIDS, the p55 TNF receptor in TRAPS, the cryopyrin in familial cold urticaria and chronic infantile neurological cutaneous articular syndrome, lead to uncontrolled activation of the inflammasomes and ultimately to unphysiologically increased cytokine release with the consecutive clinical symptoms.
Clinical featuresThis section has been translated automatically.
The clinical dermatological symptoms of hereditary periodic fever syndromes can be summarized under the clinical term "neutrophilic urticarial dermatosis". Clinically, in the active phases of the disease, there are 2.0 cm large, also larger, less itchy (rather burning) pale red spots, urticarial, flat papules or plaques that persist for about 24 hours or longer. The skin changes are always accompanied by a disturbance of the AZ, fever, joint complaints, neutrophilic leukocytosis and an increase in acute phase proteins (see the respective clinical pictures below).
DiagnosisThis section has been translated automatically.
Molecular genetic detection of mutations of the MEFV gene (FMF), MVK gene (HIDS) or the TNFRSF1A gene (TRAPS).
Differential diagnosisThis section has been translated automatically.
TherapyThis section has been translated automatically.
TablesThis section has been translated automatically.
|
Familial Mediterranean fever |
Hyper-IgD syndrome |
TRAPS |
Muckle-Wells syndrome |
CINCA syndrome |
Familial cold urticaria |
PFAPA syndrome |
Ethnicities |
Eastern Mediterranean |
Caucasian |
Caucasian |
all |
all |
all |
all |
Age of first manifestation |
< 10 J. |
< 1 J. |
< 20 J. |
neonatal |
< 1 J. |
adolescence |
< 5 J. |
Duration of fever |
1-3 days |
3-7 days |
> 1 week |
> 1 week |
|
1-2 days |
3-6 days |
Skin symptoms |
Erysipelas-like |
maculo-papular |
migratory, painful |
urticarial, urticarial vasculitis |
maculo-papular, also urticarial |
urticaria |
aphthae |
arthritis |
+++ |
+++ |
+ |
++ |
+ |
+ |
- |
Diagnosis |
- |
Serum IgD |
< TNF TYPE 1 |
- |
- |
Exposure to cold |
- |
therapy |
colchicine |
Corticosteroids |
NSAR; Etanercept |
NSAIDS |
NSAR; corticosteroids |
Corticosteroids; Ø cold |
Tonsillectomy |
amyloid |
Yes |
no |
yes yes |
yes |
yes |
yes |
yes |
Note(s)This section has been translated automatically.
LiteratureThis section has been translated automatically.
- Booshehri LM et al (2019) CAPS and NLRP3. J Clin Immunol 39:277-286.
- Braun-Falco M et al (2011) Skin involvement in autoinflammatory syndromes. JDDG 9: 232 - 245
- Cordero MD et al. (2018) Gain of function mutation and inflammasome driven diseases in human and mouse models. J Autoimmun 91:13-22.
- Dode C et al. (2003) TNFRSF1A-associated periodic syndrome (TRAPS), Muckle-Wells syndrome (MWS) and renal amyloidosis. J Nephrol 16: 435-437
- Grateau G (2003) Periodic fevers: from genetics to clinical medicine. Arch Pediatr 10: 379-384
- Gusdorf L et al. (2018) Neutrophilic urticarial dermatosis: A review. Ann Dermatol Venereol 145:735-740.
- Hachulla E (2003) Systemic urticarias. Ann Dermatol Venereol 130: 53-68
- Houten SM et al. (2003) Isoprenoid biosynthesis in hereditary periodic fever syndromes and inflammation. Cell Mol Life Sci 60: 1118-1134
- Levy R et al. (2015) Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever Registry". Annals of the Rheumatic Diseases 74: 2043-2049.
- Moltrasio C et al. ( 2022) NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: From cryopyrin function to targeted therapies. Front Immunol 13:1007705.
- Parikh SR et al. (2003) Utility of tonsillectomy in 2 patients with the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. Arch Otolaryngol Head Neck Surg 129: 670-673
- Piram M et al. (2014) Validation of the auto-inflammatory diseases activity index (AIDAI) for hereditary recurrent fever syndromes. Ann Rheum Dis 73:2168-2173.
- Romano M et al. (2022) The 2021 EULAR/American College of Rheumatology points to consider for diagnosis, management and monitoring of the interleukin-1 mediated autoinflammatory diseases: cryopyrin-associated periodic syndromes, tumor necrosis factor receptor-associated periodic syndrome, mevalonate kinase deficiency, and deficiency of the interleukin-1 receptor antagonist. Ann Rheum Dis 81:907-921.