Periodic Fever Syndrome

Define periodic fever syndrome

The condition in which patient suffers from recurring episodic fever along with inflammatory symptoms without the presence of allergy, infection, cancer, immunodeficiency is termed as a periodic fever syndrome. This condition is categorized as auto-inflammatory syndromes.

The characteristic features of the periodic fever syndrome include three or more than three episodic feverish attack within a six-month period with an interval of at least seven days without a resultant of medical illness. It is also observed that episodic interval may follow regular or irregular intervals.

The syndromes can be distinctive as it is considered that due to the defective genetic factor is involved in creating the periodic fever syndrome. It has been also observed that periodic fever syndrome is often associated with family history and the condition is termed as Familial Mediterranean Fever (FMF). The Familial Mediterranean Fever (FMF) is one of the most general periodic fever syndrome, which is carried forward due to hereditary defect.

Besides of Familial Mediterranean Fever, periodic fever syndrome also includes Systemic lupus erythematosus, juvenile arthritis or Vasculitis. (1,2,3)

Types of hereditary periodic fever syndromes

There are two types of the hereditary periodic fever syndromes, which include:

• Autosomal recessive
• Autosomal dominant

Autosomal recessive periodic fever syndromes

• The defective genetic mutation which is the key feature of the Autosomal recessive periodic fever syndromes involve both the parents by collecting one copy abnormal gene receive from each parent. Therefore, two copies of the abnormal gene are required to create the autosomal recessive periodic fever syndromes. The nature of both the genes may be same (homozygotes), but abnormal genetic mutation differs (heterozygotes). It is also necessary to mention that the parents act as asymptomatic carriers of the genetic defect. Familial Mediterranean fever (FMF) and Hyperimmunoglobulinaemia D syndrome (HIDS) are examples of autosomal recessive periodic fever syndromes.

Autosomal dominant periodic fever syndromes

In this condition, single copy of the defective gene needs to create symptoms and signs of an autosomal dominant periodic fever syndrome. This inherited condition arises due to the involvement of an affected parent, in rare case, the disease arises due to an impulsive mutation in the affected child. (3)

Symptoms

The symptoms of the periodic fever syndrome depend upon the type of the periodic fever syndrome. But one common clinical feature includes the recurring incidences of fever in the nonexistence of infection, malignancy or autoimmune disease. The episodic fever attacks vary from individual to individual, which may vary from 24 hours interval to 10 years interval. The duration of the attack also differs and it may extend from 1 hour to virtually continue for long duration depends upon the type of the syndrome. The body temperature rise from a slight elevation to marked augmentation, which can reach over 40 degrees Celsius. The fever attack may start after birth in case of early onset, whereas it may also possible to develop of the middle age for delayed onset.

In general included symptoms are:

• Definite rash syndrome,
• Joint pain and inflammation,
• Pain in abdomen
• Muscle pain
• Lethargy
• Malaise

The periodic fever syndrome can affect the quality of life, mainly if fever hits are recitative or periodic fever syndrome leads to joint or neurological complication. Even fatal complications can be arise if periodic fever syndromes come along with systemic deposition of amyloid in the body (amyloidosis). [1,3,4]

What causes the disease?

The type of periodic fever analysis is very important for detection the cause. The most common type of periodic fever syndrome is FMF, which is caused due to genetic disorders. The identified gene is the MEFV gene. The abnormal mutation of MEFV gene affects the pyrin protein, which possess a specific role in regulating inflammation. Defective mutation cause uncontrollable inflammatory symptoms along with episodic fever attacks.  Incidence of trauma, infection, menstrual cycle, or stress may provoke the episodic attacks. [1]

Diagnosis

Following differential diagnostic tests are performed:

• Physical examination along with consideration of infections, allergies, malignancy, immunodeficiencies and autoimmune diseases are needed to analyze and excluded the possibility.
• Family history analysis
• Gaslini score helps to identify the hereditary or non- hereditary involvement
• Blood test result with a high level of IgDhelps to detect the Hyperimmunoglobulinaemia D syndrome (HID).
• Genetic testing of the MEFV, TNFRSF1A and MVK genes also conduct for identification of defective gene mutation. (3)

Treatment

Usually it has been observed that periodic fever syndrome without having the specific reason, periodic fever syndromes are self-limiting and after a months to years the syndrome goes away in this own way.

Analgesic, anti-inflammatory drugs or even systemic corticosteroids are prescribed for symptomatic relief from the acute hits of inherited periodic fever syndromes. The antipyretic drugs like paracetamol or aspirin are unable to control the raising body temperature.

Some of the periodic fever syndrome like FMF cannot be alleviated, but it can be manageable with colchicine, which has to take the patient for lifelong. It has been observed that 60% of the patients are totally prevented, whereas 33% of patients are partially benefitted with colchicine, but 5% patients are ineffective against colchicine use. Colchicine is also effective to prevent amyloidosis.

But associated risk for amyloidosis may arrive or episodic attack immediately started with missing of any dose of the drug. Therefore, close monitoring to watch the patient compliance is an important factor to achieve 100% effective result.

Without consulting with doctor, patient or family member should not modify the dose. Initially, some kids require psychological support to maintain the compliance of drug therapy and also accept the perception to take medicine their entire life. The efficacy of the colchicine is restricted to preventing the episodic attacks, but unable to control the already initiated the episode, therefore it is increase of dose during episode is ineffective. [1, 3]

Prognosis

Patient with FMF usually has a normal life expectancy with good colchicine treatment prognosis in case of FMF. [1]

References

1. Periodic Fever Syndrome; Cleveland clinic; Retrieve from: http://my.clevelandclinic.org/services/orthopaedics-rheumatology/diseases-conditions/periodic-fever-syndrome

2. Am Fam Physician; Recurrent Fevers in Children: Differential Diagnosis; 2003 Feb 15;67(4):863-864. Retrieve from: http://www.aafp.org/afp/2003/0215/p863.html

3. Periodic fever syndromes; DermNet NZ; Retrieve from: http://www.dermnetnz.org/systemic/periodic-fever.html

4. Periodic Fever Syndrome; Oxford University Hospitals; Retrieve from: http://www.ouh.nhs.uk/oxparc/information/diagnoses/a-z/periodic-fever-syndromes.aspx