Presentation
Acronym PFMC Disclaimer Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. [uniprot.org]
Symptoms present at birth, and continuous. [102] Symptoms may be present at birth or early infancy. [102] Purpuric rash presenting at birth or in infancy. Vasculitis noted on skin biopsy. [autoinflammatory-search.org]
Pyrin is a protein normally present in the inflammasome. The mutated pyrin protein is thought to cause inappropriate activation of the inflammasome, leading to release of the pro-inflammatory cytokine IL-1β. [en.wikipedia.org]
Patients presenting with TRAPS commonly have northern European ancestry. [emedicine.medscape.com]
The hereditary periodic fever syndromes are autoinflammatory diseases that mostly present in childhood and are characterized by recurrent, self-limiting, seemingly unprovoked episodes of fever and systemic inflammation that occur in the absence of autoantibody [oxfordmedicine.com]
Entire Body System
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Fever
Symptoms of Periodic fever, menstrual cycle-dependent Clinical features : Imported from Human Phenotype Ontology (HPO) Abnormality of metabolism/homeostasis Fever Abnormality of prenatal development or birth Recurrent spontaneous abortion Similar Topic [familydiagnosis.com]
Format Definition A condition characterized by recurrent fevers up to 40 degrees Celsius associated with the luteal phase of the menstrual cycle. Women show menstrual cycle-dependent physiologic changes in relation to sex hormone levels. [uniprot.org]
[from OMIM ] Fever MedGen UID: 5169 • Concept ID: C0015967 • Sign or Symptom A condition characterized by an abnormally high body temperature. [ncbi.nlm.nih.gov]
Recurrent and periodic fever overview Unlike a fever of unknown origin, recurrent and periodic fevers occur regularly in repeated cycles or intermittently over a period of time. [mdedge.com]
The most common fever syndrome PFAPA does not have a genetic test, but ruling out fever syndromes that can have similar symptoms, such as HIDS, CAPS, FMF, Behcet-like familial autoinflammatory syndrome (HA20) and TRAPS is important when diagnosing PFAPA [saidsupport.org]
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Inflammation
Because ovulation triggers a significant change in the hormonal milieu that is similar to local inflammation, a 0.5 to 1.0 degree Celsius increase in basal body temperature after ovulation is commonly associated with progesterone secretion and is believed [ncbi.nlm.nih.gov]
Attacks are accompanied by blood test abnormalities showing inflammation, including high white cells, and a very high C-reactive protein (CRP). [ucl.ac.uk]
Rarely, children have recurrent pericarditis (inflammation of the outer layer of the heart), myositis (muscle inflammation), meningitis (inflammation of the membrane surrounding the brain and spinal cord) and orchitis (testicular inflammation). [my.clevelandclinic.org]
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Weakness
C4025651 • Finding Overproduction of the hormone of cortisol by the adrenal cortex, resulting in a characteristic combination of clinical symptoms termed Cushing syndrome, with truncal obesity, a round, full face, striae atrophicae and acne, muscle weakness [ncbi.nlm.nih.gov]
A few have autoantibodies, or weak positive autoantibodies, such as: Lupus anticoagulant, anti dsDNA, anticardiolipin, RNP, ANA, Some also have HLA-B51, or HLA-B15, or HLA-B39/B44 noted. [autoinflammatory-search.org]
Dosage reduction is recommended in patients who develop weakness or GI symptoms (anorexia, diarrhea, nausea, vomiting) related to drug therapy. [emedicine.medscape.com]
In rare cases, it may cause muscle weakness. The blood count (white and red blood cells and platelets) may decrease occasionally, but recovers with dose reduction. Children taking colchicine grow normally. [my.clevelandclinic.org]
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Anorexia
Dosage reduction is recommended in patients who develop weakness or GI symptoms (anorexia, diarrhea, nausea, vomiting) related to drug therapy. [emedicine.medscape.com]
Nausea, abdominal pain, anorexia, diarrhea (may be bloody). [43] Splenomegaly; lymphadenopathy. [43] 45% have arthralgias and/or arthritis–often the knees and/or ankles, but other joints can be affected. [autoinflammatory-search.org]
256000 603647 Autosomal recessive; Mitochondrial BDNF 11p14.1 {Obsessive-compulsive disorder, protection against} 164230 113505 Autosomal dominant BDNF 11p14.1 Central hypoventilation syndrome, congenital 209880 113505 Autosomal dominant BDNF 11p14.1 {Anorexia [mnglabs.com]
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Hyperthermia
[…] idiopathic generalized, susceptibility to, 6} 611942 607904 CACNA1H 16p13.3 {Epilepsy, childhood absence, susceptibility to, 6} 611942 607904 CACNA1H 16p13.3 Hyperaldosteronism, familial, type IV 617027 607904 Autosomal dominant CACNA1S 1q32.1 {Malignant hyperthermia [mnglabs.com]
Respiratoric
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Pneumonia
Onset [64] Frequent sinusitis or pneumonia, and respiratory infections. Concurrent autoimmune diseases. [64] [65] Onset in infancy-under 6 months of age. [autoinflammatory-search.org]
[…] differential diagnoses is long and includes the following, based on the initial presentation: Abdominal pain, lower quadrant predominant: Acute appendicitis, porphyria, hereditary angioedema, pancreatitis (with hypertriglyceridemia) Chest pain/pleurisy: Pneumonia [emedicine.medscape.com]
Musculoskeletal
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Muscle Weakness
weakness, and other features. [ncbi.nlm.nih.gov]
In rare cases, it may cause muscle weakness. The blood count (white and red blood cells and platelets) may decrease occasionally, but recovers with dose reduction. Children taking colchicine grow normally. [my.clevelandclinic.org]
Some patients have a headache with the onset of the rash and fever, plus asthenia (muscle weakness) and tachycardia. [58] [61] Not noted. [58] [61] [62] Not noted. [58] [61] [62] Tachycardia. [autoinflammatory-search.org]
Neurologic
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Headache
Migraine MedGen UID: 57451 • Concept ID: C0149931 • Disease or Syndrome Migraine is a chronic neurological disorder characterized by episodic attacks of headache and associated symptoms. [ncbi.nlm.nih.gov]
Severe headache occurs particularly in children, and rarely, in young boys, there can be pain and swelling of the testicles. [ucl.ac.uk]
Some patients have headaches with flares. [autoinflammatory-search.org]
Episodes are often heralded by chills and headache, a rising fever, abdominal pain, nausea, and vomiting. [emedicine.medscape.com]
About two-thirds of patients report headache, sore throat and/or mouth ulcers, and more than three quarters report swelling of the lymph nodes. About half experience abdominal pain or nausea. [mdedge.com]
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Paresis
[…] disease, recessive intermediate, A 608340 606598 Autosomal recessive GDAP1 8q21.11 Charcot-Marie-Tooth disease, axonal, type 2K 607831 606598 Autosomal dominant; Autosomal recessive GDAP1 8q21.11 Charcot-Marie-Tooth disease, axonal, with vocal cord paresis [mnglabs.com]
Treatment
It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice . [uniprot.org]
The mainstay of management is long term treatment with low doses of a tablet called colchicine. Continuous treatment with colchicine prevents or substantially reduces symptoms of FMF in at least 95%. [ucl.ac.uk]
Best management of PFAPA: steroids vs tonsillectomy vs IL-1 blockade vs no treatment. Use of colchicine for treatment or prophylaxis in FMF patients with one identified non-M694mutation or mild presentation. [clinicaladvisor.com]
What are the treatments for TRAPS? There is still no proven definitive treatment to prevent or cure the disease. [my.clevelandclinic.org]
Ilaris is already approved as a treatment for another Periodic Fever Syndrome condition – Cryopyrin-Associated Periodic Syndromes, as well as Systemic Juvenile Idiopathic Arthritis. For more information visit Novartis.com. [empr.com]
Prognosis
Prognosis Pain during ovulation does not have any dangerous consequences. External resources American College of Obstetricians and Gynecologists P.O. [drugs.com]
Unlike other PFSs, NOMID follows a chronic course with significant complications, poor overall prognosis and shortened lifespan if untreated (by IL-1 blockade therapy.) [clinicaladvisor.com]
To date few periodic syndromes remain of unknown origin like PFAPA syndrome (periodic fever, aphtous stomatitis, pharyngitis and adenitis), characterized by periodic fever attacks with early onset, of non-infective origin, with benign prognosis in the [ijponline.biomedcentral.com]
A review conducted by Ben-Chetrit and Touitou 4 attempted to explain the origin of FMF in countries far from the Middle East and to ascertain whether the disorder in these non-Mediterranean countries differed in manifestation and prognosis. [nature.com]
The prognosis depends on the development of amyloidosis. More aggressive therapy may be indicated in patients with a positive family history of amyloidosis. [emedicine.medscape.com]
Etiology
Although familial cases of PFAPA have been reported, the syndrome’s etiology isn’t fully understood. She began with a review of fever definition and pathogenesis, and used a series of case studies to introduce various fever syndromes. [mdedge.com]
Etiology of elevated serum IgD and also IgA (in 70%) recurrent fevers from decreased MVK activity not fully understood, but includes increased inflammasome activation and IL-1beta overproduction. [clinicaladvisor.com]
Periodic fevers are characterized by seemingly unprovoked, recurrent attacks of fever and severe inflammation in the absence of infectious or autoimmune etiology. [link.springer.com]
Epidemiology
Relevant External Links for HTR1A Genetic Association Database (GAD) HTR1A Human Genome Epidemiology (HuGE) Navigator HTR1A Atlas of Genetics and Cytogenetics in Oncology and Haematology: HTR1A No data available for Genatlas for HTR1A Gene A genetic variant [genecards.org]
Epidemiology: FMF: Most common inherited PFS. Predominantly affects people living in the Mediterranean region. Incidence: 1-3/10 5 in Turkey, Armenia, North Africa, Arab countries, and Italy; rare elsewhere. [clinicaladvisor.com]
Epidemiological data about inflammatory diseases are poor; generally they are quite rare diseases. No gender prevalence has been described; only some reports recorded mild predominance in males for FMF [ 6 ]. [ijponline.biomedcentral.com]
HISTORICAL EPIDEMIOLOGY Although FMF has been reported in a variety of ethnic groups, the condition primarily affects populations of the Mediterranean basin: Arabs, Armenians, Turks, Greeks, Italians, Persians, and North African Jews (Morocco, Algeria [nature.com]
Pathophysiology
Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease*. Annu Rev Immunol 2009;27(1):621–68 Stojanov S, Kastner DL (2005). "Familial autoinflammatory diseases: genetics, pathogenesis and treatment". [en.wikipedia.org]
Furthermore, disease entities based on criteria, like the PFAPA syndrome, might conceal different diseases from a pathophysiological perspective. [link.springer.com]
Patients treated with anakinra, an IL-1 receptor antagonist, exhibited rapid clinical and immunological response and improved skeletal lesions. [81] Otulipenia A growing body of research indicates that the ubiquitin pathway is important in the pathophysiology [emedicine.medscape.com]
Prevention
Prevention It usually is not necessary to prevent this mild, short-lived pain syndrome. Birth control pills prevent ovulation and can be used to prevent mid-cycle pain. [drugs.com]
We hope that early treatment may prevent development of complications of CAPS such as deafness and eye damage. [ucl.ac.uk]
In this way, episodes can usually be prevented (in 60 percent of patients completely prevented, in 33 percent partially prevented, and in about 5 percent colchicine is not effective) and amyloidosis can be prevented in 100 percent of patients. [my.clevelandclinic.org]
Colchicine prevents renal amyloidosis in FMF, but not in HIDS, TRAPS or CAPS. [clinicaladvisor.com]
MANAGEMENT AND TREATMENT Treatment of FMF is centered on prevention of painful attacks and the development of amyloidosis. [nature.com]