Periodic fever syndrome

In 1987, 12 cases of the appearance of a kind of syndrome, which manifested itself as a periodic fever accompanied by farynitis, aphthous stomatitis, and cervical adenopathy, were described. In English-speaking countries, it was designated by the initial letters of this complex of manifestations (periodic fever, aphthous stomatitis, pharingitis and cervical adenitis) - PFAPA-syndrome. Francophone same articles often call this disease Marshall Syndrome.

[1], [2], [3], [4], [5]

Epidemiology

This disease is more often observed in boys (about 60%). In general, the syndrome begins to manifest itself in about 3-5 years (mean: 2.8-5.1 years). But in this case, cases of the disease development in 2-year-old children are also common - for example, among the 8 patients studied, 6 fever attacks were observed at the age of 2 years. There was also a case of an 8-year-old girl, when for 7 months. Before contacting the doctors she had symptoms of the disease.

[6], [7], [8], [9], [10], [11]

Causes of the periodic fever syndrome

The causes of the development of the syndrome of periodic fever in our days have not yet been fully studied.

Now scientists are discussing several of the most probable causes of this disease:

• Activation of latent infections in the body (this is possible at a confluence of certain factors - due to a decrease in immunological reactivity, the dormant virus in the human body "wakes up" with the development of fever and other symptoms of the syndrome);
• passed to the chronic stage of bacterial infection of the tonsils of the palate or throat - the products of microbial activity begin to affect the immune system, which causes a fever attack;
• autoimmune nature of the pathology development - the immune system of the patient takes the cells of his own organism for foreign ones, which provokes a rise in temperature.

[12], [13], [14]

Symptoms of the periodic fever syndrome

The syndrome of periodic fever is characterized by a clearly defined frequency of febrile seizures - they are repeated regularly (mostly every 3-7 weeks).

In more rare cases, the gaps last 2 weeks or more than 7 weeks. Studies indicate that, on average, the intervals between occurring attacks first last for 28.2 days, and for a year the patient has 11.5 seizures. There is information about longer breaks - in 30 cases they lasted within 3.2 +/- 2.4 months, while the French researchers gave a period of 66 days. There are also observations in which the intervals last an average of about 1 month, and occasionally 2-3 months. Such differences in the duration of free intervals are most likely due to the fact that over time they begin to lengthen.

On average, the period between the 1 st and the last episode of an attack is 3 years and 7 months (an error of +/- 3.5 years). In general, seizures are repeated for 4-8 years. It should be noted that after the disappearance of seizures, there are no residual changes in patients, in the development, as well as the growth of such children, there are no violations.

The temperature during the attack is basically 39.5 ⁰ -40 ⁰, and sometimes even reaches 40.5 ⁰. Antipyretics help only for a short period of time. Before increasing the patient's temperature, there is often a brief prodromal period in the form of ailments with general disorders - a sense of weakness, strong irritability. A quarter of children have chills, 60% have a headache, and 11-49% have arthralgia. The appearance of pain in the abdomen, mostly not strong, is noted in half of the patients, and a fifth is observed in vomiting.

The totality of the symptoms, according to which this pathology was named, is not observed in all patients. Most often in this case, there is cervical adenopathy (88%). Cervical lymph nodes in this case increase (sometimes up to a size of 4-5 cm), to the touch they are testy and weakly sensitive. The enlarged lymph nodes become noticeable, and at the end of the attack quite quickly decrease and disappear - just in a few days. Other groups of lymph nodes remain unchanged.

Pharyngitis is also observed quite often - it is diagnosed in 70-77% of cases, and it should be noted that in some cases, the patient is dominated by weak catarrhal forms, and in others - there are overlays along with effusion.

Less common is aphthous stomatitis - the frequency of such manifestations is 33-70%.

A fever usually lasts for 3-5 days.

With febrile attacks, leukocytosis may occur in moderate forms (approximately 11-15x10 ⁹ ), and the level of ESR increases to 30-40 mm / h, as well as the level of CRP (up to 100 mg / l). Such shifts stabilize fairly quickly.

Syndrome of periodic fever in adults

This syndrome usually develops only in children, but in some cases it is diagnosed in an adult.

Complications and consequences

Among the possible complications of this syndrome:

• A general blood test shows neutropenia (a decrease in the number of white blood cells (white blood cells) in the blood);
• Frequent bouts of diarrhea;
• There are rashes on the skin;
• Joints become inflamed (arthritis develops);
• Manifestations of neurological disorders (convulsions, severe headaches, the onset of fainting, etc.).

[15], [16], [17], [18]

Diagnostics of the periodic fever syndrome

Periodic fever syndrome is usually diagnosed as follows:

• The doctor examines the patient's complaints and the history of the disease - finds out when fever has occurred, whether they have a certain periodicity (if there is, what it is). Also determine whether the patient has aphthous stomatitis, cervical lymphadenopathy or pharyngitis. Another important symptom is whether the symptoms of the disease appear in the intervals between seizures;
• Then the patient is examined - the doctor determines the increase in lymph nodes (either in palpation or in appearance (when they increase to a size of 4-5 cm)), as well as palatine tonsils. The patient has reddening of the throat, and on the mucosa of the oral cavity sometimes appear sores of a whitish color;
• The patient is taking blood for a general analysis - to determine the level of leukocytes, as well as ESR. In addition, there is a shift in the left side of the leukocyte formula. These symptoms indicate that the body has an inflammatory process;
• A biochemical blood test is also performed to determine the increase in the CRP index, and in addition to this fibrinogen, this sign is a signal of the onset of inflammation. An increase in these indicators indicates the development of an acute inflammatory reaction of the body;
• Examination in the otolaryngologist and allergologist-immunologist (for children - children's specialists of these profiles).

There are also cases of development of family forms of this syndrome - for example, two children from the same family had signs of the disease. But to find a genetic disorder, which is specific to the syndrome of periodic fever, at this stage has not yet been possible.

[19], [20]

Differential diagnosis

Periodic fever syndrome must be distinguished from tonsillitis in a chronic form that occurs with frequent periods of exacerbation and other diseases such as: juvenile idiopathic arthritis, Behcet's disease, cyclic neutropenia, familial Mediterranean fever, Hibernian familial fever, and hyperglobulinemia syndrome.

In addition, it must be differentiated with cyclic hematopoiesis, which in addition to the cause of the development of periodic fever may be an independent disease.

Difficult diagnostics of this syndrome with the so-called Armenian disease can be quite complicated.

Similar symptoms are also another rare disease - the periodic syndrome, which is associated with TNF, in medical practice denoted by the abbreviation TRAPS. This pathology has an autosomal recessive nature - it arises because the gene of the conductor 1 of the TNF is mutated.

[21], [22], [23]

Treatment of the periodic fever syndrome

The treatment of periodic fever syndrome has many unresolved issues and discussions. The use of antibiotics (penicillins, cephalosporins, macrolides and sulfonamides), non-steroidal anti-inflammatory drugs (paracetamol, ibuprofen), acyclovir, acetylsalicylic acid and colchicine proved to be ineffective, in addition to reducing fever time. On the contrary, the use of oral steroids (prednisolone or prednisolone) causes a sharp resolution of febrile episodes, although it does not prevent the development of relapses.

The use of ibuprofen, paracetamol, and colchicine in the process of treatment can not provide a stable result. It was determined that the recurrence of the syndrome goes after tonsillectomy (in 77% of cases), but the retrospective analysis performed in France showed that this procedure was effective only in 17% of all cases.

There is a variant with the use of cimetidine - a similar proposal is based on the fact that this drug can block the activity of H2 conductors on T-suppressors, and in addition stimulate the production of IL10 and inhibit IL12. These properties help stabilize the balance between T-helper (type 1 and 2). This treatment option allowed to increase the remission period in ¾ of patients with a small number of tests, but with large amounts this information was not confirmed.

Studies show that the use of steroids (eg, prednisolone in a single dose of 2 mg / kg or for 2-3 days in a decreasing dosage) quickly stabilizes the temperature, but they are not able to relieve relapses. There is an opinion that the effect of steroids can shorten the duration of the remission period, but still they are now usually chosen as a cure for the periodic fever syndrome.

Prevention

Since there is no precise information about the causes of the development of PFARA syndrome, there is no complex of methods for preventing this disease.

[24], [25], [26], [27]

Forecast

The syndrome of periodic fever is a non-infectious pathology, in which acute attacks of fever develop with high frequency. With the correct diagnosis, the prognosis is favorable - it can quickly cope with acute attacks, and in the case of benign disease the child may not even need tonsillectomy.