Periodic fever syndrome

Periodic Fever Syndrome Microchapters
Patient Information
Overview
Classification Familial Mediterranean fever Hyperimmunoglobulinemia D with recurrent fever TNF receptor associated periodic syndrome Cryopyrin-associated periodic syndrome Periodic fever, aphthous stomatitis, pharyngitis and adenitis Blau syndrome Pyogenic sterile arthritis, pyoderma gangrenosum, acne
Causes
Differential Diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: Autoinflammatory syndrome

Overview

The periodic fever syndromes (also known as autoinflammatory syndromes) are a set of genetic disorders in which the mechanisms which initiate and control inflammation are disturbed leading to uncontrolled inflammation throughout the body. The syndromes are diverse but tend to cause fever, joint pains, abdominal pains and may lead to chronic complications such as amyloidosis.

Causes

• Familial Mediterranean fever
• Hyperimmunoglobulinemia D with recurrent fever
• TNF receptor associated periodic syndrome (TRAPS)
• Cryopyrin-associated periodic syndrome (CAPS) which includes:
  • Muckle-Wells syndrome
  • Familial cold urticaria
  • Neonatal onset multisystem inflammatory disease
• Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA syndrome)
• Blau syndrome
• Pyogenic sterile arthritis, pyoderma gangrenosum, acne (PAPA syndrome)

Differential Diagnosis

• Periodic fever syndromes should be differentiated from each other.

Category of Disease	Diseases	Signs and symptoms														Laboratory findings
		Inheritance pattern	Fever duration	Frequency of attacks	Abdominal pain	Arthralgia/Arthritis	Chest pain	Skin rash	Myalgia/Body pain	Diarrhea/Vomiting	Neurologic manifestations	Conjunctivitis	Aphthous stomatitis	Lymphadenopathy	Splenomegaly	Complete blood count (CBC)	C- reactive protein (CRP)
																		Erythrocyte sedimentation rate (ESR)	Other findings	Genetic analysis
Autoinflammatory diseases	Familial mediterranean fever	Autosomal recessive/dominant	12-72 h	Weekly or 3-4 times/year	+	+	+	erysipelas-like erythema	+	+	Headache	-/+	-/+	-/+	+	Leukocytosis	↑	↑	High risk for amyloidosis	Mutation in MEFV gene
	Hyper IgD with recurrent fever	Autosomal recessive	3-7 days	Every 2-12 weeks	+	+	+	Diffuse maculopapular rash Polymorphous rash	+	+	Headache	-	+/-	+/-	+/-	Leukocytosis	↑	↑	Elevated srum level of IgD & IgA Chronic mevalonic aciduria	Mutation in MVK gene
	TNF receptor-associated periodic syndrome	Autosomal dominant	3-4 weeks	Variable	+	+	-	Migrating rash with deep pain under the areas with the rash Severe pain follows the rash path in a centrifugal pattern	-	-	Headache	+	-	+/-	+	Leukocytosis	↑	↑	Periorbital edema	Mutation in TNFRSF1A gene
	Muckle-Wells Syndrome	Autosomal dominant	2-3 days	More common during cold seasons	+	+	-	Urticaria-like rash	+	+	Headache	+	+	-	-	Leukocytosis	↑	↑	Cold-triggered attacks	Mutation in NLRP3 gene
	Familial cold urticaria	Autosomal dominant	12-24 hours, or longer	Common in cold seasons	-	+	-	Urticaria-like rash	-	-	Headache Mild hearing loss	+	+/-	-	-	Leukocytosis	↑	↑	Cold-triggered attacks	Mutation in NLRP3 gene
	Neonatal onset multisystem inflammatory disease	Autosomal dominant	Continuous	Common in cold seasons	+		+	Urticaria-like rash	+	+	Headache Aseptic meningitis Papilledema Seizure sensorineural hearing loss	+	+/-	Generalized lymphadenopathy	+	Leukocytosis	↑	↑	Intellectual disability Elevated levels of Immunoglobulins Cold-triggered attacks	Mutation in NLRP3 gene
	Pyogenic sterile arthritis, pyoderma gangrenosum, acne (Papa syndrome)	Autosomal dominant	Variable	Variable	+/-	Destructive arthritis	+/-	Pyoderma gangrenosum ulcerative lesions Severe cystic acne	+/-	+/-	-	-	-	-	-	Leukocytosis	↑	↑	High neutrophilic content of synovial fluid Negative cultures of bone and skin	Mutation in PSTPIP1 gene
	Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA)	Unkown	3-6 days	Every 21-28 days	+	+	-	-	+	+	-	-	+	Cervical lymphadenopathy	-	Leukocytosis	↑	↑	Culture negative exudative pharyngitis is a classic finding	Unknown
	Blau syndrome	Autosomal dominant	Intermittent or persistent daily fever	Variable	+/-	+	+/-	scaly plaques Non-caseating granulomatous dermatitis in Biopsy	+	+/-	Cranial neuropathies Visual problems in 80% Peripheral neuropathies	-	+	+/-	+	Leukocytosis	↑	↑	Ophthalmologic manifestations are common	Mutation in NOD2 gene

References

Stojanov S, Kastner DL. Familial autoinflammatory diseases: genetics, pathogenesis and treatment. Curr Opin Rheumatol. 2005 Sep;17(5):586-99. Review. PMID 16093838