What are the common causes of recurrent fevers in children. How are recurrent fevers diagnosed. What treatment options are available for children with recurrent fevers. How can parents manage recurrent fevers in children at home. When should parents seek medical attention for a child with recurrent fevers.

Understanding Recurrent Fevers in Children

Recurrent fevers in children can be a source of concern for parents and healthcare providers alike. Defined as three or more febrile episodes within a six-month period, occurring at least seven days apart without an apparent underlying medical cause, these fever patterns can be both regular and irregular. Let’s delve into the intricacies of this condition to better understand its implications and management strategies.

What Constitutes a Recurrent Fever?

A recurrent fever is not just any series of fevers that a child experiences. To meet the clinical definition, the following criteria must be met:

• At least three febrile episodes within six months
• Episodes occur at least seven days apart
• No identifiable medical illness causing the fevers

This pattern can be particularly distressing for families, as it often leaves them searching for answers and solutions to their child’s recurring symptoms.

PFAPA Syndrome: A Common Culprit

Among the various causes of recurrent fevers, PFAPA syndrome stands out as one of the most common diagnoses, especially in children under five years of age. But what exactly is PFAPA syndrome?

Decoding PFAPA Syndrome

PFAPA stands for:

• Periodic Fever
• Aphthous Ulcers
• Pharyngitis
• Adenopathy

This syndrome is characterized by high fevers that last for three to six days and recur every 21 to 28 days. Alongside the fever, children may experience some or all of the symptoms indicated in the acronym. Interestingly, children with PFAPA syndrome are typically well between episodes and relatively well even during the febrile periods.

Identifying PFAPA Syndrome

How can healthcare providers identify PFAPA syndrome? Here are some key features:

1. Regular fever patterns occurring every 3-4 weeks
2. High fevers lasting 3-6 days
3. Cervical adenopathy (swollen lymph nodes in the neck)
4. Small, relatively painless aphthous ulcers (often overlooked)
5. Normal health between episodes

It’s worth noting that laboratory tests are most helpful during fever episodes, when leukocytosis (increased white blood cell count) or elevated erythrocyte sedimentation rate (ESR) may be detected.

Diagnosing Recurrent Fevers: A Methodical Approach

Diagnosing the cause of recurrent fevers in children requires a systematic approach. While PFAPA syndrome is common, it’s crucial to consider other potential causes to ensure proper treatment.

Regular vs. Irregular Fever Patterns

One of the first steps in diagnosis is determining whether the fever pattern is regular or irregular. Regular patterns are less common and often point to specific conditions like PFAPA syndrome or cyclic neutropenia. Irregular patterns, on the other hand, have a broader differential diagnosis.

Laboratory Work-up for Recurrent Fevers

What tests should be performed for a child with recurrent fevers? The initial work-up typically includes:

• Complete blood count (CBC) with differential and platelet count
• Erythrocyte sedimentation rate (ESR)
• C-reactive protein (CRP) testing
• Urine culture

For children who appear ill, blood cultures may be necessary. Additional tests may be ordered based on the child’s exposure history, clinical presentation, and physical examination findings.

Beyond PFAPA: Other Causes of Recurrent Fevers

While PFAPA syndrome is a common cause of recurrent fevers in children, it’s essential to consider other potential etiologies, especially when fever patterns are irregular or accompanied by additional symptoms.

Infectious Causes

Various infectious agents can lead to recurrent fevers in children. These include:

• Viruses (e.g., Epstein-Barr virus)
• Bacteria
• Parasites

It’s worth noting that fever without other signs or symptoms is more commonly associated with viral infections than bacterial ones. Interestingly, fungal infections have not been reported to cause recurrent fevers in otherwise healthy children.

Inflammatory and Autoimmune Disorders

Several inflammatory and autoimmune conditions can manifest with recurrent fevers. These include:

• Inflammatory bowel disease
• Juvenile rheumatoid arthritis
• Behçet’s disease

ESR testing can be particularly useful in distinguishing these inflammatory disorders from hereditary periodic fever syndromes.

Rare and Unusual Causes

In some cases, recurrent fevers may be caused by rare conditions or unusual presentations of common diseases. Examples include:

• Cyclic neutropenia
• Relapsing fever
• Lymphoma
• Factitious fever (induced fever)

Diagnosing these conditions often requires specialized testing and careful clinical observation.

Treatment Approaches for Recurrent Fevers

The treatment of recurrent fevers in children varies depending on the underlying cause. For many children, especially those with PFAPA syndrome, the prognosis is generally favorable.

Managing PFAPA Syndrome

For children diagnosed with PFAPA syndrome, several treatment options have shown efficacy:

1. Single-dose prednisone (2 mg per kg) at the onset of symptoms can provide relief
2. Prophylactic cimetidine may improve symptoms in some cases
3. Tonsillectomy has been reported to alleviate symptoms in certain children

It’s important to note that while these treatments can help manage symptoms, the underlying cause of PFAPA syndrome remains unknown.

Treating Other Causes of Recurrent Fever

For other causes of recurrent fever, treatment is tailored to the specific diagnosis:

• Cyclic neutropenia: Granulocyte colony-stimulating factor can decrease the duration of neutropenia and reduce infection risk in severe cases
• Infectious causes: Appropriate antimicrobial therapy based on the identified pathogen
• Inflammatory disorders: Anti-inflammatory medications or immunomodulators as indicated

In many cases of recurrent fever without a defined underlying cause, careful monitoring and supportive care are the primary approaches.

When to Seek Medical Attention

While recurrent fevers can be concerning, not all cases require immediate medical intervention. However, there are certain situations where parents should seek prompt medical attention for their child.

Red Flags for Immediate Evaluation

Parents should contact their healthcare provider if their child with recurrent fevers exhibits any of the following:

• Signs of dehydration (dry mouth, sunken eyes, decreased urine output)
• Persistent high fever (>104°F or 40°C)
• Severe headache or neck stiffness
• Difficulty breathing
• Unusual rashes or bruising
• Persistent vomiting or abdominal pain
• Changes in mental status or behavior

These symptoms could indicate a more serious underlying condition that requires prompt evaluation and treatment.

Living with Recurrent Fevers: Guidance for Families

Dealing with recurrent fevers can be challenging for both children and their families. While medical management is crucial, there are several strategies that families can employ to cope with this condition effectively.

Home Management Techniques

Parents can help manage their child’s symptoms at home with the following approaches:

1. Ensure adequate hydration by offering frequent fluids
2. Use over-the-counter fever reducers as recommended by the healthcare provider
3. Provide comfortable, light clothing and maintain a cool room temperature
4. Offer light, easily digestible foods when the child is hungry
5. Encourage rest while allowing for gentle activities as tolerated

It’s important for parents to remember that fever itself is not harmful and is often the body’s way of fighting infection.

Emotional Support and Education

Living with recurrent fevers can be emotionally taxing for children and their families. Here are some ways to provide support:

• Educate the child about their condition in age-appropriate terms
• Maintain open communication with school staff about the child’s condition
• Connect with support groups or other families dealing with similar issues
• Encourage normal activities and routines between fever episodes
• Practice stress-reduction techniques as a family

By fostering a supportive environment and maintaining a positive outlook, families can help their child cope more effectively with recurrent fevers.

Future Perspectives in Recurrent Fever Management

As medical research continues to advance, our understanding and management of recurrent fevers in children are likely to improve. What developments can we expect in the coming years?

Emerging Research Areas

Several promising areas of research may lead to improved diagnosis and treatment of recurrent fevers:

• Genetic studies to identify markers for periodic fever syndromes
• Development of more targeted therapies for specific fever disorders
• Investigation into the potential role of the microbiome in recurrent fevers
• Improved diagnostic tools to differentiate between various causes of recurrent fever

These advancements may lead to more personalized treatment approaches and better outcomes for children with recurrent fevers.

The Role of Telemedicine

Telemedicine is increasingly playing a role in managing chronic conditions, including recurrent fevers. How might this impact care?

1. Improved access to specialists for children in remote areas
2. More frequent check-ins and adjustments to treatment plans
3. Enhanced ability to track fever patterns and symptoms over time
4. Reduced need for in-person visits, decreasing the burden on families

As telemedicine technologies continue to evolve, they may become an integral part of managing recurrent fevers in children.

Recurrent Fevers in Children: Differential Diagnosis

RICHARD SADOVSKY, M.D.

Am Fam Physician. 2003;67(4):863-864

Recurrent fevers are defined as three or more febrile episodes in a six-month period, occurring at least seven days apart, with no causative medical illness. These episodes can occur at regular or irregular intervals. John and Gilsdorf review the evaluation and differential diagnoses for recurrent fever. An overview is provided in the accompanying table.

Few diseases cause a regular pattern of recurrent fevers. The most common diagnosis associated with this fever pattern is PFAPA syndrome (i. e., periodic fever, aphthous ulcers, pharyngitis, and adenopathy). PFAPA is characterized by high fevers lasting three to six days and recurring every 21 to 28 days, accompanied by some or all of the signs noted in its name. The syndrome usually occurs in children younger than five years who present with regular fevers and cervical adenopathy. Aphthous ulcers, which are usually small and relatively painless, are the symptom most likely to be missed.

The rightsholder did not grant rights to reproduce this item in electronic media. For the missing item, see the original print version of this publication.

Children with PFAPA syndrome are well between episodes and relatively well even during episodes. Laboratory tests are helpful only during episodes, when leukocytosis or elevated erythrocyte sedimentation rate (ESR) can be detected. The cause of PFAPA is unknown, although viral or autoimmune etiologies have been suggested. Treatment at the beginning of the symptomatic period with a single dose of prednisone (2 mg per kg) relieves symptoms. Use of prophylactic cimetidine or tonsillectomy also may improve symptoms in some children.

Other causes of recurrent fevers include rare diseases such as cyclic neutropenia (which has symptoms similar to those of PFAPA) or relapsing fever, or uncommon manifestations of common diseases such as Epstein-Barr virus infection. Diagnosis of cyclic neutropenia requires obtaining frequent leukocyte counts during febrile and nonfebrile periods to document a decline in the absolute neutrophil count (less than 500 per mm³ [0.5 × 10⁹ per L]), with recovery to normal shortly after. Marrow examination done at the time of neutropenia reveals myeloid line maturation arrest. In children who have severe symptoms with cyclic neutropenia, granulocyte colony-stimulating factor decreases the duration of neutropenia and the resultant risk of infection.

Recurrent fevers that occur at irregular intervals have a lengthy differential diagnosis. Infectious causes can include viruses, bacteria, and parasites. Fever without any other sign or symptom is more common with viral infections than with bacterial infections. Fungal infections have not been reported to cause recurrent fevers in healthy children. Inflammatory or autoimmune diseases, including inflammatory bowel disease, juvenile rheumatoid arthritis, and Behçet’s disease, as well as hereditary periodic fevers, lymphoma, and factitious fever, should be considered. ESR testing is useful in distinguishing inflammatory from hereditary disorders.

The laboratory work-up in children with recurrent fever depends on the history and physical examination. The apparently healthy child needs only a complete blood cell count (CBC) with differential and platelet count, and ESR and C-reactive protein testing. Urine cultures are also useful. If the child appears ill, blood cultures should be obtained, with additional tests as indicated by potential exposure, clinical history, and physical examination. Children with normal initial evaluations and no additional signs or symptoms do not require further testing. Recurrent fevers with no defined underlying cause have a very favorable prognosis.

The authors conclude that recurrent fever often occurs without any defined etiology. Diagnostic testing should be limited, depending on a careful history and focused physical examination. Careful follow-up will help in the early identification of other presenting symptoms of serious disease. Recurrent fever in children usually resolves without any long-term adverse effects.

Periodic Fever Syndromes | Duke Health

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Overview

Fevers that persist for several days and are accompanied by other symptoms such as sore throat, abdominal pain, and/or joint pain may indicate the presence of a periodic fever syndrome. Children may have recurrent episodes of fever and symptoms as often as every three to four weeks.

Duke pediatric rheumatologists are experts in identifying the many disorders that fall under the heading of periodic fever syndromes. They may recommend treatment to control symptoms so your child can return to daily activities. In rare cases, treatment may prevent potential complications from uncontrolled inflammation.

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Understanding Periodic Fever Syndromes

Content

Periodic fever syndromes are a group of rare, often inherited conditions; there may be a family history of similar episodes. The episodes of fever are not caused by infection and they are not due to an autoimmune disease such as systemic lupus erythematosus. Periodic fever syndromes typically involve episodes of unregulated inflammation, which is why they are also known as autoinflammatory conditions.

Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome
PFAPA is probably the most common disorder. It often appears in early childhood (between the ages of 2 and 5). Children have recurrent episodes of fever, mouth sores, sore throat, and swollen lymph nodes in the neck. There tend to be regular intervals between episodes. There are no long-term complications associated with PFAPA, and treatment is recommended to minimize or eliminate symptoms and allow a return to regular activities. PFAPA may last for several years, but it often goes away on its own during the second decade of life.

Familial Mediterranean Fever (FMF)
This genetic disease mostly affects people of Mediterranean and Middle Eastern descent. It causes recurrent fevers along with pain and swelling in the abdomen, chest, or joints. Painful, severe joint swelling can make it hard to walk. It typically affects children before the age of 10. Left untreated, FMF may result in a dangerous buildup of proteins, called amyloidosis, that may lead to organ failure.

Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
This condition causes intermittent fevers plus a painful rash, chills, and muscle pain. Onset is often in childhood but may be delayed until mid-adulthood. In addition to symptoms common to other periodic fever syndromes, people with TRAPS often have associated eye symptoms including conjunctivitis and swelling around the eye. Amyloidosis may occur in some people. 

Hyperimmunoglobulin D Syndrome (HIDS)
This rare genetic condition is also known as Mevalonate Kinase-Associated Periodic Fever Syndrome. Symptoms usually start in the first year of life. It typically begins with an abrupt onset of high fever (up to 104). Associated symptoms may include skin rash, abdominal pain, vomiting, diarrhea, joint pain, and swollen neck glands.

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Diagnosis

Tests Overview

The first step will be to rule out other causes of recurrent fever, such as infection or an autoimmune disease that may have symptoms similar to periodic fever syndrome. The pediatric rheumatologist may also perform tests in order to better diagnose your child’s condition and recommend the most appropriate treatment. 

Physical Exam

Description

The doctor will examine your child’s body and look for signs associated with periodic fever syndrome, such as joint swelling, rashes, swollen glands, mouth sores, or swelling around the eyes. 

Blood and Urine Tests

Description

These and other tests determine whether infection or inflammation is present. They may include a white blood cell count, throat culture, and tests for erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Tests are often performed when your child is well, and again when your child is ill, to compare the degrees of inflammation.

Genetic Tests

Description

May help confirm a diagnosis if physical exams and lab tests indicate your child has an inherited syndrome.

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Treatments

Treatments Overview

The type of treatment your child may need will depend on the specific diagnosis. The main goal is to prevent episodes of fever and associated symptoms while minimizing the potential for side effects so your child can perform regular daily activities such as attending school. Some periodic fever syndromes require long-term treatment, including into adulthood, whereas others may resolve on their own as your child grows.

Corticosteroids

Description

PFAPA responds well to steroids like prednisone. A single dose given at the start of an attack can significantly shorten or end the attack. Steroids can also relieve symptoms caused by other periodic fever syndromes but are used on a limited basis to prevent side effects associated with long-term use.

Colchicine

Description

As the treatment of choice for FMF, colchicine reduces the severity of the attacks and helps prevent amyloidosis. It is safe to use for prolonged periods and in pregnancy.

Biologics

Description

Biologic therapy is indicated in certain periodic fever syndromes. Biologics are protein medications that are given as an injection under the skin, like an insulin injection, or by infusion through an intravenous (IV) catheter. In general, periodic fever syndromes are associated with increased inflammatory proteins. Biologics address these proteins more directly than corticosteroids.

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Content

Partners with Pediatric Specialists
When necessary, our pediatric rheumatologists partner with other Duke pediatric specialists including dermatologists, nephrologists, and ophthalmologists to manage your child’s condition.

Support for Your Child and Family
Periodic fever syndromes are especially disruptive to school-age children because they cause recurrent and painful attacks can last for days or weeks. If symptoms or treatment sessions are interfering with school, our dedicated social worker can arrange accommodations to help your child keep up with their schoolwork.

National Partners in Research and Treatment
Our rheumatologists participate in a national network of doctors devoted to expanding our knowledge of these rare conditions. When appropriate, we consult with our peers to help confirm a diagnosis or share treatment discoveries.

This page was medically reviewed on 10/30/2018 by

C. Egla Rabinovich, MD, MPH
| Pediatric Rheumatologist

Fever in children. Causes of development and methods of treatment

Body temperature is regulated by thermosensitive neurons localized in the preoptic and anterior hypothalamus. These neurons are responsible for changes in body temperature in the same way as neural connections with cold and heat receptors located in the skin and muscles. Thermoregulatory responses are highly variable, mediated through a variety of mechanisms, and include directing blood flow in the skin vasculature, increased or decreased sweat secretion, regulation of extracellular fluid volume (via arginine vasopressin), or behavioral responses such as seeking warmth or cool ambient temperature. Normally, there is a circadian temperature rhythm or diurnal variations in body temperature within adjustable limits. Body temperature is lower in the morning and approximately 1°C higher in the afternoon and late afternoon.

Fever is a controlled increase in body temperature through mechanisms that regulate normal temperature. The difference is that the “thermostat” of the body is reset to a high temperature. Depending on which disease accompanies fever (infectious, connective tissue disease, malignant process), regulatory mechanisms are triggered in response to endogenous pyrogens, which, in turn, trigger the production of cytokines such as interleukin (IL) 1β and IL-6 , tumor necrotizing factor α, β-interferons and interferon-γ. Stimulated leukocytes and other cells produce lipids that also serve as endogenous pyrogens. The most well-studied lipid mediator is prostaglandin E2. Most endogenous pyrogenic molecules are too large to cross the blood-brain barrier. However, near the hypothalamus, the functions of the blood-brain barrier are insufficient, which allows neurons to contact circulating factors through a network of capillaries.

Microbes, microbial toxins and other microbial waste products are among the most common exogenous pyrogens that, when ingested, stimulate the functions of macrophages and other cells to produce endogenous pyrogens leading to fever. Endotoxin can directly influence thermoregulation in the hypothalamus and stimulate the release of endogenous pyrogens. Some substances formed in the body are not pyrogens, but are able to stimulate the formation of endogenous pyrogens. Such substances include antigen-antibody complexes in the presence of complement, as well as complement components, lymphocyte products, bile acids, and androgenic steroid metabolites. Fever can be the result of infections, vaccination, exposure to biological agents (granulocyte – macrophage – colony stimulating factor, interferons, interleukins), tissue damage (heart attack, pulmonary embolism, trauma, intramuscular injections, burns), malignant diseases (leukemia, lymphoma, metastatic diseases) , taking certain drugs (drug fever, cocaine, amphotericin B), diffuse connective tissue diseases, rheumatic diseases (systemic lupus erythematosus, rheumatoid arthritis), granulomatous diseases (sarcoidosis), endocrine (thyrotoxicosis, pheochromocytoma), metabolic disorders (uremia, gout) , genetic disorders (familial Mediterranean fever) and other unknown and poorly understood causes.

An increase in body temperature in response to microbial attack represents a response that has been observed in reptiles, fish, birds, and mammals. In humans, an increase in body temperature is accompanied by a decrease in the reproduction of microorganisms and an increase in the inflammatory response. Most of the evidence to date suggests that fever is an adaptive response and should only be treated in selected situations.

Although the nature of the temperature curve alone is not often helpful in making a specific diagnosis, observation of fever can provide useful information to the clinician. In general, a single isolated peak is not associated with an infectious disease. Such a peak can be observed with parenteral administration of blood products, drugs, certain procedures or catheter manipulations with an infected skin surface. Temperatures above 41°C are rarely due to an infectious cause. Very high fever (> 41°C) is most commonly central fever (due to CNS dysfunction involving the hypothalamus), malignant hyperthermia, drug fever, fever due to overheating.

Temperature below normal (< 36 °C) is most often associated with exposure to cold, hypothyroidism, overdose of antipyretics.

Intermittent or intermittent fever (daily fluctuations in t° max and t° min of at least 1 ° C, but the minimum body temperature never drops to normal values) is defined as hectic or may be due to sepsis. The remaining persistent fever is persistent, and fluctuations in t ° do not exceed 0.5 ° C per day. With relapsing (laxative) fever, fluctuations in t ° exceed 0.5 ° C during the day, but it does not return to normal. Recurrent (relapsing) fever is separated by intervals of normal temperature, for example, in three-day malaria, fever is observed on the 1st and 3rd days ( Plasmodium vivax ), four days – on the 1st and 4th days ( Plasmodium malariae ). The biphasic nature of Bactrian camel fever indicates the presence of a single disease with two definite periods of fever of more than 1 week. The classic example is polio. Biphasic fever is also observed in leptospirosis, dengue fever, yellow fever, African hemorrhagic fever.

The dependence of heart rate on body temperature can be quite informative. Relative tachycardia, when the pulse rises in proportion to body temperature, is usually observed in non-communicable diseases or infections in which the toxin determines the clinical manifestations. Relative bradycardia (dissociation of pulse and temperature), when the pulse remains low during fever, suggests drug fever, typhoid, brucellosis, leptospirosis. Febrile bradycardia may also be the result of conduction disturbances involving the heart in acute rheumatic fever, Lyme disease, viral myocarditis, and infective endocarditis.

Most infections lead to various lesions causing an inflammatory response and subsequent release of endogenous pyrogens. The appointment of etiotropic antimicrobial therapy can lead to rapid elimination of bacteria. However, if tissue damage is severe, the inflammatory response and fever may continue for several days after eradication of all microbes.

Fever occurs in various infectious diseases with a wide range of severity. In healthy children, benign febrile illnesses include viral infections (rhinitis, pharyngitis, pneumonia), bacterial infections (otitis media, pharyngitis, impetigo), which usually respond well to antibiotic therapy and are not life-threatening. Risk groups include young children, with chronic diseases, immunodeficiency states. Some bacterial infections such as sepsis, meningitis, pneumonia, pyelonephritis, if left untreated, can be severe and have poor outcomes.

Fever without a specific focus usually presents a diagnostic dilemma for pediatricians, especially in children of the first 1.5–2 years of life, making it difficult to differentiate between serious bacterial infections and viral diseases.

Fever in children under 3 months of age always suggests the presence of a serious bacterial disease (sepsis, meningitis, urinary tract infection, gastroenteritis, osteomyelitis, otitis, omphalitis, mastitis, etc. ). Bacteremia may be due to group B streptococcus, Listeria monocytogenes , Salmonella spp., Esherichia coli , Neisseria 15 Streptococcus pneumonia , Haemophilus influenzae type B, Staphylococcus aureus . Children under the age of 3 months with fever, symptoms of intoxication should be hospitalized, blood cultures, urine, cerebrospinal fluid should be examined and parenteral antimicrobial therapy should be started immediately. Unlike bacterial infections, viral diseases tend to be seasonal.

Regardless of age, a fever accompanied by a petechial rash indicates a high risk of life-threatening bacterial infections. 8-10% of patients with fever and petechiae had severe bacterial infections, 7-10% had meningococcal sepsis or meningitis. The disease caused by H.influenzae type B may also present with fever and a petechial rash. Treatment tactics include hospitalization, blood and cerebrospinal fluid culture, and the appointment of appropriate antimicrobial therapy.

Many physicians use the term “fever of unknown origin” for patients presenting for examination who do not have an obvious infection or a non-infectious diagnosis. In most of these children, the appearance of additional symptoms after a relatively short period of time makes the infectious nature of the disease obvious. Therefore, this term is more often used in patients with fever that is not identifiable after 3 weeks in the outpatient setting or after 1 week in the hospital.

The causes of the so-called fever of unknown origin can be infectious processes and diseases of the connective tissue (autoimmune and rheumatic). It is necessary to exclude a neoplastic process. Most cases of fever of unknown or unrecognized origin are the result of an atypical course of common diseases. Since at the beginning there may be no clinical and laboratory signs of a certain disease, the diagnosis in some cases is made only after prolonged observation. Causes of fever of unknown origin in a more detailed examination included salmonellosis, tuberculosis, syphilis, Lyme disease, atypical protracted course of common viral diseases, infectious mononucleosis, cytomegalovirus infection, hepatitis, histoplasmosis. Inflammatory bowel disease, rheumatic fever, Kawasaki disease can also cause fever of unknown origin. In these cases, it is recommended to re-examine the patient after a certain period of time.

In children under 6 years of age, fever of unknown origin is associated with infection of the respiratory or urogenital tract, localized infection (abscess, osteomyelitis), juvenile rheumatoid arthritis, rarely leukemia. Adolescents are more likely to have tuberculosis, an inflammatory process in the intestines, an autoimmune process, and lymphoma. The empiric use of antibiotics should be avoided. In unclear cases, hospitalization may be required for x-ray and laboratory examinations, closer observation, temporary relief from the anxiety of the child and parents. Once fully adequately assessed, antipyretics may be indicated for fever control and symptomatic treatment.

Fever less than 38–38.5°C in previously healthy children generally does not require treatment. If this level is exceeded, the state of health of patients worsens, and the appointment of antipyretics improves the condition. Antipyretics generally do not change the course of infectious diseases in normal children and are symptomatic. Heat production associated with fever increases oxygen consumption, carbon dioxide production, and cardiac output. Thus, fever may worsen heart failure in patients with heart disease or chronic anemia (eg, sickle cell anemia), pulmonary insufficiency in patients with chronic lung disease, and metabolic disorders in children with diabetes, congenital metabolic disorders. Moreover, in children between 6 months. and 5 years, the risk of febrile seizures is increased, and in children with idiopathic epilepsy, febrile illness may increase the frequency of seizures. Antipyretics are prescribed in high-risk patients, ie. having chronic cardiopulmonary diseases, metabolic, neurological diseases, and children with a high risk of developing febrile seizures. Hyperpyrexia (> 41°C) is associated with severe infections, hypothalamic disorders, and central nervous system hemorrhage and always requires antipyretics.

When choosing antipyretics for children, it is especially important to focus on drugs with the lowest risk of side effects. Currently, only paracetamol and ibuprofen fully meet the criteria for high efficacy and safety and are officially recommended by the World Health Organization and national programs in pediatric practice as antipyretics [1-3]. Acetaminophen, aspirin, and ibuprofen are hypothalamic cyclooxygenase (COX) inhibitors that inhibit the synthesis of PGE-2. These drugs are considered equivalent effective antipyretics. Since aspirin is associated with Reye’s syndrome in children and adolescents, it is not recommended for use in the treatment of fever. Paracetamol and ibuprofen can be prescribed to children from the first months of life (from 3 months of age). Recommended single doses: paracetamol – 10-15 mg / kg, ibuprofen – 5-10 mg / kg. Re-use of antipyretics is possible not earlier than after 4-5 hours, but not more than 4 times a day.

It should be noted that the mechanism of action of these drugs is somewhat different. Paracetamol has an antipyretic, analgesic and very slight anti-inflammatory effect, since it blocks COX mainly in the central nervous system and does not have a peripheral effect, it is metabolized by the cytochrome P-450 system. The delay in the excretion of the drug and its metabolites can be observed in violation of the functions of the liver and kidneys. If a child has a deficiency of glucose-6-phosphate dehydrogenase and glutathione reductase, the administration of paracetamol can cause hemolysis of red blood cells, drug-induced hemolytic anemia.

Ibuprofen has a pronounced antipyretic, analgesic and anti-inflammatory effect. Ibuprofen is effective against fever in the same way as paracetamol [4–6]. A number of studies have shown that the antipyretic effect of ibuprofen at a dose of 7.5 mg/kg is higher than that of paracetamol at a dose of 10 mg/kg and acetylsalicylic acid at a dose of 10 mg/kg [7]. Ibuprofen blocks COX both in the central nervous system and in the focus of inflammation (peripheral mechanism), which determines its antipyretic and anti-inflammatory effect. As a result, the phagocytic production of mediators of the acute phase, including IL-1 (endogenous pyrogen), decreases. A decrease in the concentration of IL-1 also contributes to the normalization of temperature. The analgesic effect of ibuprofen is determined by both peripheral and central mechanisms, which makes it possible to effectively use ibuprofen for mild and moderate sore throat, pain with tonsillitis, acute otitis media, and toothache [8]. An indication for the appointment of ibuprofen is also hyperthermia after immunization.

Due to its high toxicity, amidopyrine has been excluded from the nomenclature of drugs. The use of analgin in many countries of the world is sharply limited due to the risk of developing agranulocytosis. In urgent situations, such as hyperthermic syndrome, acute pain in the postoperative period, and others that are not amenable to other therapy, parenteral use of analgin and metamizole-containing drugs is acceptable.

Comparison in double-blind, randomized trials with multiple doses of antipyretics showed that the incidence of adverse events was similar between ibuprofen and paracetamol (8–9%) [3]. The results of a large randomized study of more than 80,000 children showed that the use of ibuprofen compared with paracetamol does not increase the risk of hospitalization associated with gastrointestinal bleeding, renal failure or anaphylaxis. When using ibuprofen and paracetamol in children with bronchial asthma [3], it has been shown that the use of ibuprofen, compared with acetaminophen, does not increase the risk of bronchospasm in children with bronchial asthma who do not have indications of aspirin intolerance, which indicates the relative safety of ibuprofen in children with bronchial asthma .

According to the experts of IC “MAKS” (Vladimir), paracetamol and ibuprofen are most often used in pediatric practice (Table 1).

We used Nurofen for children (ibuprofen) in 95 children aged 3 months and older. up to 10 years old. The indication was fever in acute respiratory infections, acute otitis media, tonsillopharyngitis, obstructive bronchitis, bronchiolitis, pneumonia. 43 children of the first three years of life were hospitalized in the regional children’s hospital due to the severity of the condition. In 20 children, acute respiratory infections occurred against the background of mild to moderate bronchial asthma without indications of aspirin intolerance, in 37 children obstructive bronchitis and bronchiolitis were diagnosed. The average value of the initial axillary temperature was 39.1 ± 0.6 °С. Nurofen for children was prescribed at the rate of 5 mg/kg, on the first day – 3-4 times, on the second day – 2-3 times; the third day and beyond – according to indications. Most children were prescribed the drug for no more than 2 days. In 40-60 minutes after taking the drug, the temperature decreased to 37.9 ± 0.4 °C, after 90-120 minutes – to 37.3 ± 0.5 °C. Adverse events were noted in 2 children in the form of an allergic rash, in 1 child – abdominal pain, exacerbation or provocation of bronchospasm was not observed in any case. In 6 children, the effect of taking ibuprofen was minimal and short-lived: 2 children were prescribed diclofenac, 4 others received parenteral lytic mixture. The drug was rated as effective 90.7% of physicians and 93.7% of parents.

In 84 patients, short-term use of ibuprofen and paracetamol did not increase the risk of developing toxic changes in the kidneys [3]. An increase in the level of urea nitrogen and creatinine occurs in children who initially had a risk of developing complications from the side of the kidneys due to relevant diseases (renal failure, congenital heart failure, liver dysfunction) or a pronounced clinical picture of dehydration.

Thus, when using antipyretics, it is necessary to clearly take into account the indications with the identification of the causes of fever, age dose, premorbid background.

Fever

The state of the body, characterized by a rise in body temperature above normal, is called fever. Normally, the temperature of the human body is maintained at a level of about 37 ° C, however, in some (often infectious) diseases, a protective and adaptive reaction occurs, which is based on an increase in body temperature with the obligatory preservation of the thermoregulation mechanism. This property is a hallmark of fever from hyperthermia (overheating). Pyrogens cause fever – substances that enter the body during infection (exogenous pyrogens) or are formed by cells of the immune system as a result, for example, of inflammation (endogenous pyrogens).

Fever always passes in three stages:

1. Rise in temperature – blood vessels constrict, skin becomes pale, chills, muscle tremors, metabolism in muscles increases. At this stage, heat production is much higher than heat transfer.
2. Temperature retention – the mechanisms of heat production and heat transfer are balanced – the temperature can be fixed for hours, days or weeks. Skin vessels dilate, the skin ceases to be pale and becomes hot to the touch, chills and trembling go away. At this time, a person experiences a feeling of heat.
3. Drop in temperature – either a sharp or gradual decrease in body temperature is possible. At this stage, heat transfer significantly exceeds heat production, profuse sweating occurs and diuresis increases. This stage begins in case of exhaustion of exogenous reserves or cessation of production of endogenous pyrogens.

There are several types of fever:

• Relapsing (laxative) type is characterized by diurnal changes in temperature, which does not drop to normal;
• Intermittent (intermittent) type characterized by rapid diurnal fluctuations in temperature, which falls to normal and rises again;
• Constant fever – slight fluctuations in elevated temperature during the day;
• Relapsing fever – constantly elevated temperature for one or more days, then its reduction to normal and repeated increase;
• Perverse fever – a rise in temperature in the morning is characteristic;
• Incorrect fever – temperature fluctuations during the day occur without any dependence.