Examination algorithm for fever of unknown origin. When to start treatment

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FEVER OF UNCLEAR GENESIS: IS THE DECODING REAL?

Dvoretsky L.I.

The term “fever of unknown origin” (FOU) refers to frequently occurring clinical practice situations in which fever is the main or only sign of various diseases, the diagnosis of which remains unclear after the usual, and in some cases, additional examination. The range of diseases underlying LNG is quite wide and includes various diseases of an infectious nature, malignant tumors, systemic vasculitis, as well as other diseases of various origins. In a small proportion of patients, the cause of fever remains undeciphered. LNG is based on common diseases with an unusual course. The diagnostic search for LNG includes the identification of additional clinical and laboratory signs that determine the nature of the targeted examination using the most informative diagnostic methods for the given situation. The question of the advisability of prescribing treatment, including a trial, before deciphering the LNG should be decided individually, depending on the specific clinical situation.

The term "fever of unknown genesis" (FUG) implies common clinical conditions wherein fever is a main or sole sign of different diseases whose diagnosis remains unclear after routine and, in some cases, additional studies. The range of diseases underlying FUG is rather wide and includes different diseases of infectious origin, malignant tumors, systemic vasculitis and other diseases of various genesis. FUG is caused by common diseases having an unusual course. In FUG, diagnostic search includes identification of additional clinical and laboratory signs that determine the nature of a goal-oriented examination by using the diagnostic methods which are informative for a specific condition. Whether it is advisable to prescribe treatment, including presumptive one, and to decipher FUG should be determined on an individual basis as a specific clinical situation requires.

L.I. Dvoretsky MMA named after. THEM. Sechenov

I.M.Sechenov Noscow Medical Academy

Even ancient doctors knew that an increase in body temperature was one of the signs of many diseases, which were often simply called “fever.” After the German clinician Wunderlich pointed out the importance of measuring body temperature in 1868, thermometry became one of the few simple methods for objectifying and quantifying the disease. After the introduction of thermometry, it was no longer customary to say

that the patient is suffering from a “fever.” The doctor's task was to determine the cause of the fever. However, the level medical technologies of the past did not always make it possible to reliably determine the cause of febrile conditions, especially long-term ones. Many clinicians of the past, who based their diagnosis only on personal experience and intuition, have earned themselves a high medical reputation precisely thanks to the successful diagnosis of febrile diseases. As old diagnostic methods improve and new ones emerge, progress has been made in deciphering the causes of many cases of fevers. However, to this day, prolonged fevers of unknown origin remain one of the diagnostic problems in clinical practice.

Probably, each clinician had to observe more than one patient with prolonged fever, which was the main or only sign of the disease, the diagnosis of which remained unclear after conducting the usual, and in some cases, additional examination. Such situations give rise to

a number of additional problems associated not only with the uncertainty of the diagnosis and delay of treatment for an indefinite period, but also with the patient’s long stay in the hospital, a large volume of examinations, often expensive, and the patient’s loss of trust in the doctor. In this regard, to designate such situations and highlight them in special group, requiring a specific approach, was proposed

the term "fever of unknown origin" (FOU). This term has firmly entered the clinical lexicon and has become widespread in the medical literature, including number and in one of the most popular

reference and bibliographic publications "Index Medicus". Clinical practice and analysis of the literature indicate ambiguity in the interpretation and arbitrary use of the term LNG by some clinicians without taking into account the degree of temperature increase, its duration and other signs. This, in turn, makes it difficult to develop a standard approach to diagnostic search. Meanwhile, at one time, criteria were precisely defined that made it possible to evaluate a clinical situation as LNG:

– the patient has a temperature of 38°C (101°F) or higher;

– duration of fever for 3 weeks or more or periodic rises in temperature during this period;

– uncertainty about the diagnosis after examination using generally accepted

(routine) methods.

Thus, a unique syndrome (LNG syndrome) was identified, which differs from other cases of increased body temperature. Based on these criteria, cases of so-called unclear low-grade fevers, which are often incorrectly designated as LNG, should not be classified as LNG. Meanwhile, unclear low-grade fevers occupy a special place in clinical practice and require a different diagnostic approach. In most cases, vague low-grade fevers are one of the manifestations of autonomic dysfunction, although they can also be caused by the presence of an infectious-inflammatory process (tuberculosis). An important criterion is the duration of fever for at least 3 weeks, and therefore short-term increases in temperature, even of unknown origin, do not meet the criteria for LNG. The last criterion (uncertainty of the diagnosis) is decisive and allows us to interpret the situation as LNG, since the information obtained during a standard (routine) examination of the patient does not allow us to decipher the cause of the fever.

The allocation of patients with LNG to a special group serves primarily practical purposes. It is necessary for doctors to develop the skills of a rational diagnostic search using adequate informative methods research based on knowledge of the characteristics of diseases manifested by LNG. The range of these diseases is quite extensive and includes diseases that fall within the competence of a therapist, surgeon, oncologist, infectious disease specialist and other specialists. However, until the true nature of LNG is deciphered, patients, as a rule, are in general therapeutic departments, less often in specialized departments, where, depending on the nature of the existing symptoms, they are admitted with suspected pneumonia or infection. urinary tract, rheumatic and other diseases.

The nosological structure of the causes of LNG has recently undergone changes. Thus, among the “febrile” diseases, some forms of infections in immunodeficiencies began to appear, various types nosocomial infections, boreliosis, mononucleosis syndrome, etc.

WITH Taking this into account, it was proposed to distinguish 4 groups of LNG:

1) “classical” version of LNG, which includes, along with previously known, some new diseases (Lyme disease, syndrome chronic fatigue); 2) LNG due to neutropenia;

3) nosocomial LNG; 4) LNG associated with HIV infection (microbacteriosis, cytomegalovirus infection, cryptococcosis, histoplasmosis).

This article will discuss mainly group 1 LNG. They are based not on rare or unusual pathological processes, but on diseases well known to doctors, the peculiarities of their course

which is the predominance of febrile syndrome. These are, as a rule, “common diseases with an unusual course.”

Analysis of literature data and our own clinical experience indicate that most often LNG is based on diseases that can be conditionally divided into several groups. Specific gravity

each of these groups fluctuates, according to different authors, which can be determined by various

factors (specifics of hospitals, in which patients are examined, level of examination, etc.). So, the cause of LNG can be:

generalized or local infectious and inflammatory processes – 30–50% of all cases of LNG;

tumor diseases – 20–30%;

systemic connective tissue lesions (systemic vasculitis) – 10–20%;

other diseases, varied in etiology, pathogenesis, methods of diagnosis, treatment and prognosis - 10–20%;

in approximately 10% of patients the cause of fever cannot be deciphered

despite a thorough examination using modern informative methods.

An increase in body temperature during these pathological processes is ultimately due to the effect of endogenous pyrogen on the thermoregulation center located in the anterior hypothalamus. Endogenous pyrogen, according to modern concepts, belongs to interleukins and is produced by macrophages, monocytes, neutrophils and, to a lesser extent, eosinophils as a result of the immune response to various microbial and non-microbial antigens, immune complexes, sensitized T-lymphocytes, endotoxins of various origins, cellular decay products. Cells of various malignant tumors (lymphoproliferative tumors, kidney tumors, liver tumors, etc.) also have the ability to produce endogenous pyrogen. The fact that tumor cells produce pyrogen has been proven experimentally and is confirmed in clinical conditions by the disappearance of fever after surgical removal tumor or initiation of chemotherapy for a lymphoproliferative disease.

Infectious and inflammatory diseases

The presence of LNG is traditionally associated by most doctors primarily with an infectious process and prompts the prescription of antimicrobial drugs even before obtaining the examination results. Meanwhile, infectious and inflammatory processes underlie LNG in less than half of the patients in this group.

Tuberculosis

Various forms of tuberculosis (TB) continue to be one of the common causes of LNG, and among infectious and inflammatory processes, according to most publications, they occupy a leading place. The latter is the cause of LNG in approximately half of patients after kidney transplantation. Infectious mononucleosis may proceed atypically and take a protracted course in the absence of altered lymphocytes and lymphadenopathy. A similar course gave rise to the so-called chronic mononucleosis syndrome. PCR has high sensitivity and specificity for detecting the virus.

A special group of infectious pathologies in cases of LNG is HIV infection, the spread of which over the past decades in many countries has changed the structure of the causes of LNG. In this regard, a diagnostic search for LNG should, apparently, necessarily include examination for the presence of not only HIV infection, but also those infections that are often associated with AIDS (microbacteriosis, coccidioidomycosis, histoplasmosis, etc.).

Tumor diseases

The second place in the structure of causes of LNG is occupied by tumor processes of various localizations, including hemoblastosis. The most frequently diagnosed are lymphoproliferative tumors (lymphogranulomatosis, lymphosarcoma), kidney cancer, and liver tumors (primary and metastatic). Among other tumors, bronchogenic cancer, cancer of the colon, pancreas, stomach and some other localizations are detected.

According to the data available in the literature, there was practically no tumor localization that was not detected in cases of LNG of “tumor nature.” Taking into account the likelihood of the presence of a tumor of any localization in LNG, the oncological search in these patients should be aimed not only at the most vulnerable “tumor targets”, but also at other organs and tissues.

The main difficulties in timely recognition of the tumor process in patients with LNG are usually due to minimal local manifestations or their absence. In addition, the oncological search is often delayed due to the prevailing view of doctors on fever as a manifestation of a mainly infectious process, and therefore sequentially prescribed antibacterial drugs, which do not affect the temperature.

In some cases, nonspecific syndromes such as erythema nodosum(especially recurrent), hypertrophic osteoarthropathy, migrating thrombophlebitis and some others. Unfortunately, these signs are not always correctly assessed and are interpreted as paraneoplastic only in retrospect.

The mechanism of fever during tumor processes is probably associated with the production of various pyrogenic substances (interleukin-1, etc.) by tumor tissue, and not with decay or perifocal inflammation.

One of the first signs of treatment effectiveness after starting therapy with cytostatic drugs for some hemoblastoses, such as lymphogranulomatosis, or surgical removal of the tumor, is the normalization of temperature. It is also possible that lymphokines with pyrogenic properties are produced by lymphocytes that are activated in response to the development of the tumor process. Fever does not depend on the size of the tumor and can be observed both with a widespread tumor process and in patients with the presence of one small tumor node. In this regard, it is appropriate to mention a case of LNG in a patient we observed with pheochromoblastoma, identified only during postmortem histological examination of the adrenal gland.

Oncological search in patients with LNG should include non-invasive examination methods

(ultrasonic, computed tomography, nuclear magnetic resonance), radioisotope scanning lymph nodes, skeleton, organs abdominal cavity, puncture biopsies,

endoscopic methods, including laparoscopy, and, if necessary, diagnostic laparatomy. Immunological research methods should be used to identify some specific tumor markers, in particular o-fetoprotein ( primary cancer liver), CA 19–9 (pancreatic cancer), CEA (colon cancer), PSA (prostate cancer).

Identification of the above markers will allow for a more targeted diagnostic search to exclude tumor disease.

Systemic diseases

This group of diseases ranks third in frequency among the causes of LNG and is represented mainly by diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Still's disease in adults, various forms of systemic vasculitis (arteritis nodosa, temporal arteritis, etc.), so called cross syndromes (Overlaps).

The usual diagnostic signs of the above diseases are insufficiently expressed or absent in febrile debuts of SLE and other systemic vasculitis when the fever precedes the onset articular syndrome or other systemic disorders. In such situations, suspicion of a systemic pathology, which determines the direction of the diagnostic search, may arise during dynamic monitoring of patients after identifying other clinical and laboratory signs. At the same time, it is important to correctly assess all symptoms that seem nonspecific or are usually associated

with the fever itself (myalgia, muscle weakness, headache, etc.). Thus, the combination of these symptoms with fever, especially with an increase in ESR, gives reason to suspect diseases such as dermatomyositis (polymyositis), polymyalgia rheumatica, and temporal arteritis. Polymyalgia rheumatica may at the initial stages manifest itself as fever in combination with pain in the proximal parts of the shoulder and pelvic girdle. Attention should be paid to the elderly and old age patients, a sharp increase in ESR. Polymyalgia rheumatica is often combined with temporal arteritis, characterized by the appearance of localized headaches, thickening of the temporal

arteries with weakening or absence of their pulsation. Verification of the diagnosis is possible with the help of a biopsy of the so-called temporal complex, during which it is possible to examine the skin, muscle tissue, temporal artery. At high probability disease, trial treatment with glucocorticoids in small doses (15–20 mg/day) is possible.

The effectiveness of the latter for this pathology is so specific that it may have

diagnostic value. However, the use of glucocorticoids as a trial of treatment should be avoided without a reasonable suspicion of systemic disease.

Still's disease in adults is more often diagnosed as a cause of prolonged fever - a disease with a less defined nosological framework and without specific laboratory signs.

Along with fever, the obligatory symptoms are arthritis (or arthralgia in the onset), maculopapular rash, and neutrophilic leukocytosis. Pharyngitis, lymphadenopathy, enlarged spleen, serositis, and myalgia are common. Rheumatoid and antinuclear factors are absent. This symptom complex makes one suspect various infections, sepsis and prescribe massive antimicrobial therapy, which turns out to be ineffective. Diagnosis is made rather by excluding infections and other systemic diseases.

Among the causes of LNG, rheumatic fever with the absence of microorganisms in the blood (abacterial endocarditis) and changing auscultatory symptoms remains relevant. The fever is resistant to antibiotics but can be treated with salicylates and glucocorticoids.

Other diseases

This heterogeneous group includes the most diverse diseases in etiology, diagnostic methods, treatment and prognosis. According to many authors, LNG in a number of patients may be based on diseases such as Crohn's disease, nonspecific ulcerative colitis, diverticulitis, thyroiditis, granulomatous diseases (sarcoidosis, granulomatous hepatitis), thrombophlebitis of the veins of the leg and pelvis, pulmonary embolism, nonspecific pericarditis, benign peritonitis (periodic disease) chronic alcoholic hepatitis and a number of other diseases. The peculiarity of these diseases, diverse in their origin, is atypical course, manifested mainly by a febrile syndrome without clearly defined organ symptoms, which makes it difficult to decipher the nature of LNG.

Vascular thrombosis

In some patients, fever may be the only or one of the main manifestations of thrombophlebitis of the deep veins of the extremities, pelvis, or recurrent pulmonary embolism. Such situations occur more often after childbirth, bone fractures, surgical interventions, if available intravenous catheters, in patients with atrial fibrillation, heart failure. In case of deep vein thrombosis, qualified Doppler examination of the corresponding vessels may have some diagnostic value. Heparin can completely stop or reduce fever within 48–72 hours, while antibiotics are not effective. Taking into account

Therefore, if this pathology is suspected, it is possible to prescribe a trial treatment with heparin, the effect of which may have diagnostic value and determine the further management of patients.

Thyroiditis

In almost all publications, among the diseases detected in LNG, there are isolated cases thyroiditis, in particular its subacute forms. Local symptoms and signs of dysfunction of the thyroid gland that are usual for subacute thyroiditis are not leading in these situations. Absent or weak expression pain syndrome at first does not allow the doctor to include this disease in the diagnostic search. In this regard, sufficient attention is not always paid to the examination of the thyroid gland (examination, palpation), which could determine the direction of the diagnostic search. Sometimes it is possible to obtain information (usually retrospectively) about short-term pain or discomfort in the neck. To exclude thyroiditis in cases of LNG, ultrasound examination of the thyroid gland and scanning may be useful.

Drug fevers

Fever accounts for 3–5% of adverse drug reactions, and is often the only or main complication.

Drug fevers can occur at various intervals (days, weeks) after the drug is prescribed and do not have any specific signs that distinguish them from fevers of other origins. The only sign of the medicinal nature of fever should be considered its disappearance after discontinuation of the suspected drug.

Normalization of temperature does not always occur in the first days, but often several days after discontinuation, especially in case of violations drug metabolism, slow excretion of the drug, as well as damage to the kidneys and liver. However, in most cases, if the high temperature persists for a week after discontinuation of the drug, the medicinal nature of the fever becomes unlikely

Fever most often occurs when using the following groups medicines:

– antimicrobial drugs (penicillins, cephalosporins, tetracyclines, isoniazid, nitrofurans, sulfonamides, amphotericin B);

– cytostatic drugs (bleomycin, asparaginase, procarbazine);

– cardiovascular drugs (alphamethyldopa, quinidine, procainamide, hydralazine);

– drugs acting on the central nervous system (diphenylhydantoin, carbamazepine, chlorpromazine, haloperidol, thioridazine);

– anti-inflammatory drugs (aspirin, ibuprofen, tolmetin);

– various groups of drugs, including iodide, antihistamines, clofibrate, allopurinol, levamisole, metoclopramide, cimetidine, etc.

Artificial fevers

Artificial fevers are caused by manipulation with a thermometer, as well as by ingestion or injection under the skin or into the urinary tract of various substances with pyrogenic properties. In such situations, most often we are talking about a special type of mental disorder with hypochondriacal manifestations, characterized by a painful concentration on the state of one’s own health, careful scrupulous observation of the slightest changes in well-being and condition (body temperature, blood pressure, intestinal function, etc.). Such patients are characterized by a certain type of behavior that is difficult to explain from a generally accepted point of view, for example, the desire for multiple examinations, often invasive (some patients insist on surgical interventions). Patients believe that they are suspected of malingering and underestimate the severity of their condition, the seriousness and danger of the disease. Perhaps, in this regard, they strive to demonstrate more obvious and objective signs of the disease, such as fever, bleeding, thereby trying to attract the attention of doctors. The behavior described should not be considered

All diagnostic doctors sooner or later encounter the pathological condition of a patient - fever of unknown origin. Both for the doctor these conditions require increased attention, and for the patient they are associated with constant worry and growing distrust of modern medicine. However, fevers of unknown origin (ICD-10 code R50) have been known for a long time. This article is about the pathology itself, the reasons for its occurrence and diagnostic methods. And also about the diagnostic search algorithm for fever of unknown origin, which is used by modern diagnosticians.

Why does the temperature rise

Thermoregulation of the human body is carried out at a reflex level and indicates the general condition of the body. An increase in temperature is a response of the body with a protective-adaptive mechanism.

The following levels of body temperature are typical for humans:

• Normal - from 36 to 37°C.
• Subfebrile - from 37 to 37.9°C.
• Febrile - from 38 to 38.9°C.
• Pyretic - from 39 to 40.9 °C.
• Hyperpyretic - from 41°C and above.

The mechanism of increasing body temperature is triggered by pyrogens - low molecular weight proteins that act on the neurons of the hypothalamus, which leads to an increase in the production of heat in the muscles. This leads to chills, and heat transfer is reduced due to narrowing of the blood vessels in the skin.

Pyrogens are exogenous (bacterial, viral and non-bacterial in nature, for example, allergens) and endogenous. The latter are produced by the body itself, for example, neurons of the hypothalamus or the cells themselves of various malignant and benign neoplasms.

In addition, pyrogens in the form of interleukins are produced by immune response cells - macrophages, monocytes, neutrophils, eosinophils, T-lymphocytes. They help our body cope with infections and ensure the suppression of the vital activity of pathogenic agents in conditions of elevated body temperature.

General information

Fever of unknown origin is one of the most complex pathologies, which is not so rare (up to 14% of cases in the practice of internal medicine). In general, this is a patient's condition when:

• An increase in temperature of more than 38.3 °C is observed, which is the main (usually the only) symptom of the patient’s clinical condition.
• It lasts for more than 3 weeks.
• This fever is of unknown origin (no cause has been found). Even after 1 week of diagnostic search using conventional and additional techniques.

In accordance with the international classification of diseases, the code for fever of unknown origin is ICD-10 R50 (fever of unknown origin).

Background

Since ancient times, fever has been understood as a condition accompanied by an increase in body temperature above subfebrile. With the advent of thermometry, it has become important for the doctor not only to detect fever, but also to determine its causes.

But until the end of the 19th century, fever of unknown origin remained the cause of death for many patients. First studies of this disease were carried out at Peter Bent Brigham Hospital (USA, 1930).

Only in the mid-60s of the last century did this clinical condition become widely recognized, when R. Petersdorf and R. Beeson published the results of studies of 100 patients over 2 years (only in 85 the cause of fever was established). At the same time, the code R50 for fever of unknown origin was added to ICD-10.

But until 2003, there was no classification of fevers of this type. It was this year that diagnosticians Roth A.R. and Basello G.M. (USA) a classification of fevers of unknown origin and an algorithm for diagnostic search for the causes of its occurrence were proposed.

In the article we will provide only a general overview of etiological possible reasons emergence clinical picture such a pathology.

Symptomatic picture

The symptoms of such a fever follow from its definition: a temperature above subfebrile, which lasts more than 2 weeks (constant or episodic), and the usual diagnostic techniques the cause was not determined during the first week.

Fever can be acute (up to 15 days), subacute (16-45 days), chronic (more than 45 days).

According to the temperature curve, fever is:

• Constant (temperature fluctuates within 1 degree during the day).
• Laxative (temperature fluctuations from 1 to 2 degrees during the day).
• Intermittent (periods of normal and high temperature within 1-3 days).
• Hectic (daily or over several hours temperature changes of 3 degrees).
• Recurrent (periods of elevated temperature are followed by periods with normal body temperature).
• Undulating (gradual, day after day, increase in temperature and the same decrease).
• Incorrect or atypical (temperature fluctuations without visible patterns).
• Perverse (temperature higher in the morning than in the evening).

Sometimes fever is accompanied by pain in the heart, suffocation, sweating, and chills. Most often, fever is the only symptom of the disease.

Fever of unknown origin: diagnostic search algorithm

The developed algorithm for searching for the causes of pathology includes the following stages: examination and examination of the patient, diagnostic concept, formulation of diagnosis and confirmation of diagnosis.

At the first stage, the most important thing in establishing the causes of fever of unknown origin (ICD-10 R50) is to compile a detailed medical history. It is necessary to study the characteristics of the pathology: the presence of chills, sweating, additional symptoms and syndromes. At this stage, routine laboratory and instrumental examinations are prescribed.

If at this stage the diagnosis is not established, proceed to the next stage of the algorithm for fever of unknown origin - a diagnostic search and formulation of a preliminary diagnostic concept based on all available data. The task is to develop a rational plan for subsequent examinations using optimally informative methods within the framework of the diagnostic concept.

At subsequent stages, all accompanying symptoms are identified, as well as the leading additional syndrome, which determines the probable range of pathologies and diseases. Then the diagnosis and causes of the pathological condition of fever of unknown origin, code R50 according to ICD-10, are established.

It is difficult to establish the cause of these conditions, and the diagnostician must have a sufficient level of knowledge in all areas of medicine, as well as follow an algorithm of actions for fevers of unknown origin.

When to start treatment

Prescribing treatment for patients with fever of unknown origin (ICD-10 code R50) until the diagnostic search is fully deciphered is a far from straightforward question. It must be considered individually for each patient.

Mostly, in the stable condition of a patient with fever of unknown origin, the doctor’s recommendations are reduced to the use of anti-inflammatory drugs. non-steroidal drugs. The prescription of antibacterial therapy and glucocorticosteroids is considered an empirical approach, which is unacceptable in this case. The use of this group of drugs can lead to generalization of the infection and worsen the patient's condition.

Prescribing antibiotics without sufficient justification can also lead to systemic pathologies of connective tissue (blood, bones, cartilage).

The issue of trial treatment can only be discussed if it is used as a diagnostic method. For example, prescribing tuberculostatic drugs to exclude tuberculosis.

If thrombophlebitis or pulmonary embolism is suspected, it is advisable to administer drugs that help reduce hematocrit (heparin).

What tests may be ordered?

After analyzing the medical history and initial examination results, the doctor may prescribe the following studies:

• General urine analysis.
• General and biochemical blood test.
• Blood coagulogram, hematocrit analysis.
• Aspirin test.
• Testing nerve transmission and reflexes.
• Thermometry for 3 hours.
• Mantoux reaction.
• X-ray of the lungs.
• Echocardiographic studies.
• Ultrasound examination abdominal cavity and genitourinary system.
• Magnetic resonance and computed tomography of the brain.
• Consultations with specialized specialists - gynecologist, urologist, neurologist, otolaryngologist.

Additional Research

Additional tests and studies may be needed.

Causes of the clinical picture

According to statistics, the causes of fever syndrome of unknown origin in 50% of cases are various infectious and inflammatory processes, in 30% - various tumors, 10% - systemic diseases (vasculitis, collagenosis) and 10% - other pathologies. Moreover, in 10% of cases the cause of fever cannot be determined during the patient’s lifetime, and in 3% of cases the cause remains unclear even after the patient’s death.

Briefly, the causes of such conditions can be:

• Infections genitourinary tract, streptococcal infections, pyelonephritis, abscesses, tuberculosis and so on.
• Inflammatory processes in connective tissues - rheumatism, vasculitis.
• Tumors and neoplasms - lymphoma, cancer of the lungs and other organs, leukemia.
• Diseases of a hereditary nature.
• Metabolic pathologies.
• Damage and pathologies of the central nervous system.
• Pathologies of the gastrointestinal tract.

In approximately 15% of cases, the true cause of fever remains undeciphered.

Drug fever

For fever of unknown origin, it is important to have full information about the patient taking any medications. Quite often, an increase in body temperature is evidence of the patient's increased sensitivity to medications. In this case, the temperature may rise some time after taking the drug.

In case of discontinuation of the drug, if the fever has not stopped within 1 week, its medicinal origin is not confirmed.

Towards the emergence feverish state may lead to:

Modern classification

The nosology of fever of unknown origin code ICD-10 R50 has undergone some changes in recent decades. Types of fever have appeared in immunodeficiency states, mononucleosis, and boreliosis.

In the modern classification, there are four groups of fevers of unknown origin:

• The classic type, which, along with previously known diseases (“common diseases with an unusual course”) includes chronic fatigue syndrome and Lyme disease.
• Fever due to neutropenia (abnormalities in the blood count in the direction of a decrease in the number of neutrophils).
• Nosocomial fevers (bacterial origin).
• Conditions associated with HIV (microbacteriosis, cytomegalovirus, cryptococcosis, histoplasmosis).

Let's sum it up

The range of pathologies that underlie fever of unknown origin is very wide and includes diseases of the most different groups. This is based on common diseases, but with an atypical course. That is why the diagnostic search for this pathology includes additional clinical diagnostic procedures aimed at identifying leading additional syndromes. On their basis, it is then possible to perform a preliminary check and establish the true genesis of the patient’s pathological condition.

Information flows to it from thermoreceptors located in various organs and fabrics. The thermoregulation center, in turn, regulates the processes of heat production and heat transfer in the body through nerve connections, hormones and other biologically active substances. When thermoregulation is disrupted (in animal experiments, when the brain stem is transected), body temperature becomes excessively dependent on the ambient temperature (poikilothermia).

The state of body temperature is affected by changes in heat production and heat transfer due to various reasons. If body temperature rises to 39 °C, patients usually experience malaise, drowsiness, weakness, headache and muscle pain. At temperatures above 41.1 °C, children often experience seizures. If the temperature rises to 42.2 °C or higher, a irreversible changes in brain tissue, apparently due to protein denaturation. Temperatures above 45.6 °C are incompatible with life. When the temperature drops to 32.8 °C, consciousness is impaired, at 28.5 °C atrial fibrillation begins, and even greater hypothermia causes fibrillation of the ventricles of the heart.

If the function of the thermoregulatory center in the preoptic area of ​​the hypothalamus is impaired ( vascular disorders, more often hemorrhages, encephalitis, tumors) endogenous central hyperthermia. It is characterized by changes in daily fluctuations in body temperature, cessation of sweating, lack of response when taking antipyretic drugs, impaired thermoregulation, in particular the severity of a decrease in body temperature in response to its cooling.

In addition to hyperthermia caused by dysfunction of the thermoregulatory center, increased heat production may be associated with other reasons. It is possible, in particular, with thyrotoxicosis (body temperature can be 0.5-1.1 ° C above normal), increased activation of the adrenal medulla, menstruation, menopause and other conditions accompanied by endocrine imbalance. Hyperthermia can also be caused by extreme physical exertion. For example, when running a marathon, body temperature sometimes rises to 39-41 °C. The cause of hyperthermia may also be a decrease in heat transfer. In this regard, hyperthermia is possible when congenital absence sweat glands, ichthyosis, common skin burns, as well as taking medications that reduce sweating (M-anticholinergics, MAO inhibitors, phenothiazines, amphetamines, LSD, some hormones, especially progesterone, synthetic nucleotides).

Most often, the exogenous cause of hyperthermia is infectious agents (bacteria and their endotoxins, viruses, spirochetes, yeasts). It is believed that all exogenous pyrogens affect thermoregulatory structures through an intermediary substance - endogenous pyrogen (EP), identical to interleukin-1, which is produced by monocytes and macrophages.

In the hypothalamus, endogenous pyrogen stimulates the synthesis of prostaglandins E, which change the mechanisms of heat production and heat transfer by enhancing the synthesis of cyclic adenosine monophosphate. Endogenous pyrogen contained in brain astrocytes can be released during cerebral hemorrhage or traumatic brain injury, causing an increase in body temperature, and neurons responsible for slow-wave sleep can be activated. The latter circumstance explains lethargy and drowsiness during hyperthermia, which can be considered as one of the protective reactions. At infectious processes or acute inflammations hyperthermia plays an important role in the development of immune responses, which can be protective, but sometimes lead to an increase in pathological manifestations.

Permanent non-infectious hyperthermia (psychogenic fever, habitual hyperthermia) - permanent low-grade fever (37-38 ° C) for several weeks, less often - several months and even years. The temperature rises monotonously and does not have a circadian rhythm, is accompanied by a decrease or cessation of sweating, lack of response to antipyretic drugs (amidopyrine, etc.), and impaired adaptation to external cooling. Characterized by satisfactory tolerance of hyperthermia and preservation of work capacity. Permanent non-infectious hyperthermia most often occurs in children and young women during periods emotional stress and is usually regarded as one of the signs of vegetative dystonia syndrome. However, especially in older people, it can also be a consequence of organic damage to the hypothalamus (tumor, vascular disorders, especially hemorrhage, encephalitis). A variant of psychogenic fever can apparently be considered Hines-Bannick syndrome (described by Hines-Bannick M.), which occurs as a consequence of autonomic imbalance, manifested by general weakness (asthenia), permanent hyperthermia, severe hyperhidrosis, and goose bumps. May be triggered by mental trauma.

Temperature crises (paroxysmal non-infectious hyperthermia) are sudden increases in temperature to 39-41 ° C, accompanied by a chill-like state, a feeling of internal tension, facial hyperemia, and tachycardia. The elevated temperature persists for several hours, after which a logical decrease usually occurs, accompanied by general weakness and weakness, noted for several hours. Crises can occur against the background normal temperature body or prolonged low-grade fever (permanent-paroxysmal hyperthermia). With them, changes in the blood are uncharacteristic, in particular its leukocyte formula. Temperature crises are one of the possible manifestations of autonomic dystonia and dysfunction of the thermoregulatory center, which is part of the hypothalamic structures.

Malignant hyperthermia is a group of hereditary conditions characterized by a sharp increase in body temperature to 39-42 °C in response to the administration of inhalation anesthetics, as well as muscle relaxants, especially ditilin, while insufficient muscle relaxation and the occurrence of fasciculations in response to the administration of ditilin are noted. The tone of the masticatory muscles often increases, creating difficulties for intubation, which can serve as a reason to increase the dose of a muscle relaxant and (or) anesthetic, leading to the development of tachycardia and in 75% of cases to generalized muscle rigidity (rigid form of reaction). Against this background, one can note high activity

creatine phosphokinase (CPK) and myoglobinuria, severe respiratory and metabolic acidosis and hyperkalemia develop, ventricular fibrillation may occur, blood pressure decreases, marbled cyanosis appears, and there is a threat of death.

The risk of developing malignant hyperthermia during inhalation anesthesia is especially high in patients suffering from Duchenne myopathy, central core myopathy, Thomsen's myotonia, chondrodystrophic myotonia (Schwartz-Jampel syndrome). It is assumed that malignant hyperthermia is associated with the accumulation of calcium in the sarcoplasm of muscle fibers. The tendency to malignant hyperthermia is inherited in most cases in an autosomal dominant manner with varying penetrance of the pathological gene. There is also malignant hyperthermia, inherited in a recessive manner (King's syndrome).

Laboratory tests in cases of malignant hyperthermia reveal signs of respiratory and metabolic acidosis, hyperkalemia and hypermagnesemia, increased levels of lactate and pyruvate in the blood. Among the late complications of malignant hyperthermia, massive swelling is noted skeletal muscles, pulmonary edema, disseminated intravascular coagulation syndrome, acute renal failure.

Neuroleptic malignant hyperthermia, along with high body temperature, is manifested by tachycardia, arrhythmia, blood pressure instability, sweating, cyanosis, tachypnea, while water-electrolyte imbalance occurs with an increase in the concentration of potassium in the plasma, acidosis, myoglobinemia, myoglobinuria, increased activity of CPK, AST, ALT , signs of DIC syndrome appear. Muscle contractures appear and increase, and coma. Pneumonia and oliguria are added. In pathogenesis, the role of impaired thermoregulation and disinhibition of the dopamine system in the tubero-infundibular region of the hypothalamus is important. Death occurs most often after 5-8 days. An autopsy reveals acute dystrophic changes in the brain and parenchymal organs. The syndrome develops due to long-term treatment antipsychotics, but it can develop in patients with schizophrenia who have not taken antipsychotics, and rarely in patients with parkinsonism who have been taking L-DOPA drugs for a long time.

Chill syndrome is an almost constant feeling of chilliness in the whole body or in its individual parts: in the head, back, etc., usually combined with senestopathies and manifestations of hypochondriacal syndrome, sometimes with phobias. Patients are afraid of cold weather, drafts, and usually wear excessively warm clothes. Their body temperature is normal; in some cases, permanent hyperthermia is detected. Considered as one of the manifestations of vegetative dystonia with a predominance of activity parasympathetic division autonomic nervous system.

For the treatment of patients with non-infectious hyperthermia, it is advisable to use beta- or alpha-blockers (phentolamine 25 mg 2-3 times a day, pyrroxan 15 mg 3 times a day), general restorative treatment. For persistent bradycardia and spastic dyskinesia, belladonna preparations (bellataminal, belloid, etc.) are prescribed. The patient should give up smoking and alcohol abuse.

Fever of unknown origin

Fever of unknown origin (FOU) refers to clinical cases characterized by a persistent (more than 3 weeks) increase in body temperature above 38 ° C, which is the main or even the only symptom, while the causes of the disease remain unclear, despite intensive examination (routine and additional laboratory tests). techniques). Fever of unknown origin can be caused by infectious and inflammatory processes, oncological diseases, metabolic diseases, hereditary pathologies, systemic diseases connective tissue. The diagnostic task is to identify the cause of the increase in body temperature and establish an accurate diagnosis. For this purpose, an extensive and comprehensive examination of the patient is carried out.

Fever of unknown origin

Fever of unknown origin (FOU) refers to clinical cases characterized by a persistent (more than 3 weeks) increase in body temperature above 38 ° C, which is the main or even the only symptom, while the causes of the disease remain unclear, despite intensive examination (routine and additional laboratory tests). techniques).

Thermoregulation of the body is carried out reflexively and is an indicator general condition health. The occurrence of fever (> 37.2°C for axillary measurements and > 37.8°C for oral and rectal measurements) is associated with the body’s response, protective and adaptive reaction to the disease. Fever is one of the most early symptoms many (not only infectious) diseases, when others have not yet been observed clinical manifestations diseases. This causes difficulties in diagnosing this condition.

To establish the causes of fever of unknown origin, more extensive research is required. diagnostic examination. The start of treatment, including trial treatment, before the true causes of LNG are established, is prescribed strictly individually and is determined by a specific clinical case.

Causes and mechanism of development of fever

Fever lasting less than 1 week usually accompanies various infections. Fever lasting more than 1 week is most likely due to some serious illness. In 90% of cases, fever is caused by various infections, malignant neoplasms and systemic connective tissue lesions. Fever of unknown origin may be caused by an atypical form common illness, in some cases the reason for the increase in temperature remains unclear.

The mechanism for increasing body temperature in diseases accompanied by fever is as follows: exogenous pyrogens (bacterial and non-bacterial in nature) affect the thermoregulation center in the hypothalamus through endogenous (leukocyte, secondary) pyrogen - a low molecular weight protein produced in the body. Endogenous pyrogen affects the thermosensitive neurons of the hypothalamus, leading to a sharp increase in heat production in the muscles, which is manifested by chills and a decrease in heat transfer due to the narrowing of skin blood vessels. It has also been experimentally proven that various tumors (lymphoproliferative tumors, liver tumors, kidney tumors) can themselves produce endogenous pyrogen. Violations of thermoregulation can sometimes be observed with damage to the central nervous system: hemorrhages, hypothalamic syndrome, organic lesions brain.

Classification of fever of unknown origin

There are several variants of the course of fever of unknown origin:

• classic (previously known and new diseases (Lyme disease, chronic fatigue syndrome);
• nosocomial (fever appears in patients admitted to the hospital and receiving intensive care, 2 or more days after hospitalization);
• neutropenic (number of neutrophils, candidiasis, herpes).
• HIV-associated (HIV infection in combination with toxoplasmosis, cytomegalovirus, histoplasmosis, mycobacteriosis, cryptococcosis).

Body temperature is classified according to the level of increase:

• subfebrile (from 37 to 37.9 °C),
• febrile (from 38 to 38.9 °C),
• pyretic (high, from 39 to 40.9 ° C),
• hyperpyretic (excessive, from 41°C and above).

The duration of fever can be:

• acute - up to 15 days,
• more detailed,
• chronic – more than 45 days.

Based on the nature of changes in the temperature curve over time, fevers are distinguished:

• constant - for several days there is a high (

39°C) body temperature with daily fluctuations within 1°C (typhus, lobar pneumonia, etc.);

laxative – during the day the temperature fluctuates from 1 to 2°C, but does not reach normal levels (for purulent diseases);

intermittent – ​​with alternating periods (1-3 days) of normal and very high body temperature (malaria);

hectic – there are significant (more than 3°C) daily or at intervals of several hours temperature changes with sharp changes (septic conditions);

relapsing - a period of increased temperature (up to 39-40°C) is replaced by a period of subfebrile or normal temperature (relapsing fever);

wavy - manifested in a gradual (from day to day) increase and a similar gradual decrease in temperature (lymphogranulomatosis, brucellosis);

incorrect - there is no pattern of daily temperature fluctuations (rheumatism, pneumonia, influenza, cancer);

perverted - morning temperature readings are higher than evening ones (tuberculosis, viral infections, sepsis).

Symptoms of fever of unknown origin

The main (sometimes the only) clinical symptom of fever of unknown origin is a rise in body temperature. For a long time, fever may be asymptomatic or accompanied by chills, excessive sweating, heart pain, and suffocation.

Diagnosis of fever of unknown origin

The following criteria must be strictly observed when diagnosing fever of unknown origin:

• The patient's body temperature is 38°C or higher;
• fever (or periodic rises in temperature) has been observed for 3 weeks or more;
• The diagnosis has not been determined after examinations using generally accepted methods.

Patients with fever are difficult to diagnose. Diagnosis of the causes of fever includes:

To identify the true causes of fever, additional studies are used simultaneously with generally accepted laboratory tests. For this purpose the following are appointed:

• microbiological examination of urine, blood, nasopharyngeal swab (allows to identify the causative agent of infection), blood test for intrauterine infections;
• isolation of a viral culture from body secretions, its DNA, titers of viral antibodies (allows you to diagnose cytomegalovirus, toxoplasmosis, herpes, Epstein-Barr virus);
• detection of antibodies to HIV (enzyme-linked immunosorbent complex method, Western blot test);
• microscopic examination of a thick blood smear (to rule out malaria);
• blood test for antinuclear factor, LE cells (to exclude systemic lupus erythematosus);
• performing a bone marrow puncture (to exclude leukemia, lymphoma);
• computed tomography of the abdominal organs (exception tumor processes in the kidneys and pelvis);
• skeletal scintigraphy (detection of metastases) and densitometry (determination of bone tissue density) for osteomyelitis, malignant tumors;
• examination of the gastrointestinal tract using radiology diagnostics, endoscopy and biopsy (for inflammatory processes, tumors in the intestine);
• carrying out serological reactions, including indirect hemagglutination reactions with the intestinal group (for salmonellosis, brucellosis, Lyme disease, typhoid);
• collection of data on allergic reactions to drugs (if a drug disease is suspected);
• study of family history in terms of the presence of hereditary diseases (for example, familial Mediterranean fever).

To make a correct diagnosis of fever, a repeated medical history may be taken, laboratory tests, which at the first stage could be erroneous or incorrectly assessed.

Treatment of fever of unknown origin

If the patient's fever is stable, treatment should be withheld in most cases. Sometimes the issue of conducting a trial treatment for a patient with fever is discussed (tuberculostatic drugs for suspected tuberculosis, heparin for suspected deep vein thrombophlebitis, pulmonary embolism; antibiotics fixed in bone tissue for suspected osteomyelitis). The prescription of glucocorticoid hormones as a trial treatment is justified in cases where the effect of their use can help in diagnosis (if subacute thyroiditis, Still's disease, polymyalgia rheumatica is suspected).

It is extremely important when treating patients with fever to have information about possible previous medication use. The reaction to taking medications in 3-5% of cases can be manifested by an increase in body temperature, and be the only or main clinical symptom of hypersensitivity to drugs. Drug fever may not appear immediately, but after a certain period of time after taking the drug, and is no different from fevers of other origins. If drug fever is suspected, discontinuation is required. this drug and patient monitoring. If the fever disappears within a few days, the cause is considered clarified, and if the elevated body temperature persists (within 1 week after stopping the medication), the medicinal nature of the fever is not confirmed.

There are different groups of drugs that can cause drug fever:

• antimicrobials (most antibiotics: penicillins, tetracyclines, cephalosporins, nitrofurans, etc., sulfonamides);
• anti-inflammatory drugs (ibuprofen, acetylsalicylic acid);
• medicines used for gastrointestinal diseases (cimetidine, metoclopramide, laxatives containing phenolphthalein);
• cardiovascular drugs (heparin, alpha-methyldopa, hydralazine, quinidine, captopril, procainamide, hydrochlorothiazide);
• drugs acting on the central nervous system (phenobarbital, carbamazepine, haloperidol, chlorpromazine thioridazine);
• cytostatic drugs (bleomycin, procarbazine, asparaginase);
• other drugs (antihistamines, iodide, allopurinol, levamisole, amphotericin B).

Fever of unknown origin - treatment in Moscow

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Use of Nurofen to clarify the etiology of fever of unknown origin

Pediatrician practice, March, 2007

L.I. Vasechkina, T.K. Tyurin, pediatric department of the Moscow Regional Research Clinical Institute named after. M.F. Vladimirsky

The problem of fever of unknown origin (FOU) in children remains relevant for many years. Despite this, until recently, standardized protocols for the examination and treatment of this pathology have not been developed. The difficulties of standardization are due to the fact that LNG is a child’s individual response to a number of external and internal factors, combining reactions of the immune, nervous and endocrine systems.

Among the children entering the pediatric department of the Moscow Regional Research Clinical Institute named after. M.F. Vladimirsky (MONIKI) from hospitals in the Moscow region, the annual proportion of patients with LNG is 1-3%. As a rule, the diagnosis of LNG is established in children with a body temperature above 37.4°C, recorded for more than 3 weeks, while the data from the clinical and laboratory examination do not allow us to clarify the nosological form of the disease.

In recent years, changes in the age and sex structure of LNG have been observed: there has been an increase in the number of boys with LNG, and in the age structure, compared with the previously traditional predominance of LNG in adolescents, an increase in the proportion of children under the age of 5 years and in the prepubertal period has been recorded. The identified dynamics of LNG required an analysis of this nosology to develop new approaches to clarify the etiological factor and correct treatment regimens.

We analyzed 70 case histories of children with LNG aged from 1.5 to 15 years, of which 33 were boys and 37 were girls. Patients were admitted for examination with complaints of low-grade fever for a long time (from 3 months to 1 year) malaise, weight loss, fatigue, loss of appetite.

The main goal of the study was to identify the focus of chronic infection, diagnose hormonal and neurological disorders, exclude oncological diseases and diffuse diseases connective tissue.

The examination plan included a set of laboratory tests (clinical and biochemical blood tests, analysis for inflammatory markers, general analysis and functional tests urine, coprogram, hormonal profile, ELISA test for infections), instrumental studies(ECG, ECHO-CG, EEG, ultrasound, according to CT or MRI indications), consultations with specialists (neurologist, otolaryngologist, geneticist).

As a result of a comprehensive examination, the main etiological factor of LNG was identified in most patients, the relief or correction of which was accompanied by normalization of body temperature. We found that among the causes of LNG, the first ranking place is occupied by vegetative-vascular dystonia with a violation of thermoregulation of central origin; second - various foci of infection, third - allergic syndrome(Table 1).

Table 1. Structure of etiological factors of prolonged fever depending on gender

In almost half of the children (46.5%), the underlying disease was accompanied by the presence of a chronic focus of infection (chronic tonsillitis - 23%; urogenital infection - 17%; tuberculosis infection - 8%). When tested for infections using ELISA, antibodies to the Epstein-Bar virus, cytomegalovirus, and pathogens of chlamydia and mycoplasma infections were detected in almost all children. In half of the aged patients (53%) the most common combination was vegetative-vascular dystonia and damage to the upper gastrointestinal tract (chronic gastroduodenitis, chronic esophagitis). In children under three years of age, allergic syndrome predominated, more often in the form of polyvalent food allergy.

We cannot ignore the fact that in half (50%) of children with LNG, upon examination, diagnostically significant (6-8 points) Bates criteria values ​​were identified, which made it possible to establish the presence of undifferentiated connective tissue dysplasia. Further analysis of the discovered phenomenon is necessary, but it can already be assumed that this phenotype is an indicator of neurological and endocrine dysfunctions.

The results of our own observations do not always agree with the data of other studies, according to which the most common cause of LNG is infections of the upper sections respiratory tract, diseases of bones and joints, pneumonia, cardiac and intra-abdominal infections. In our opinion, in the development of fever of unknown origin, a significant role is played by the combination of somatic pathology with neurovegetative dysfunctions, in which the leading factor in LNG is thermoregulation disorders not of inflammatory, but of regulatory etiology.

In our study, the diagnosis of thermoregulation disorder of central origin was confirmed by the presence of minor neurological symptoms and EEG abnormalities. The use of a complex of neurotropic drugs in these patients was accompanied by normalization of temperature.

According to modern concepts, there is a “set point” for the temperature balance of the body - a conglomerate of neurons in the preoptic region of the anterior part of the hypothalamus near the bottom of the third ventricle. Fever is a thermoregulatory increase in "core" temperature, which represents the body's organized and coordinated response to illness or other injury. During fever, the pyrogen affects the set point in the central nervous system, which begins to perceive the existing temperature as low and stimulates all responsible systems to increase it.

Most often the pyrogen has endogenous origin, it is secreted by phagocytic leukocytes. This happens not only in infectious diseases: the main trigger for the formation of endogenous pyrogen is phagocytosis of microorganisms, antigen-antibody complexes, dead or damaged cells, and cellular fragments. It is also formed in diseases of connective tissue, tumors, and allergies (Fig. 1).

Figure 1. Scheme of the pathogenesis of LNG in the presence of an inflammatory process

Primary pyrogens initiate fever by stimulating one's own cells to produce endogenous pyrogens. Secondary pyrogens (IL-1, 6, interferon-a, etc.), synthesized by leukocytes, act on receptors in the hypothalamus, as a result of which the sensitivity of the neurons of the thermoregulation center to cold and heat signals changes.

However, there are other mechanisms for increasing body temperature (Fig. 2).

Figure 2. Scheme of the pathogenesis of LNG in cases of disturbance of thermoregulation of central genesis

Evidence for fever regulation is the existence of an upper limit, as well as the presence of circadian rhythms. It is known that the minimum body temperature is recorded at 3 a.m., the maximum at 3 a.m. The circadian rhythm is established after 2 years, and it is more noticeable in children than in adults. It is more pronounced in girls than in boys. The presence of emotional hyperthermia has been proven. Young children attract special attention. The cause of LNG in them is quite often a violation of thermoregulation due to excessive wrapping. Thus, residual organic disorders of the nervous system, most often having their origins in perinatal period, may serve as risk factors for dysfunction of the thermoregulatory center.

Taking into account the above, it can be argued that one of the urgent tasks when examining children with LNG is to resolve the question: the leading etiological factor is inflammatory process in the body (localized or diffuse) or a violation of thermoregulation of central origin?

To accomplish this task, a test with antipyretic drugs is used, since this eliminates the factor of endogenous pyrogens from the mechanism of temperature increase. Previously, aspirin or analgin tests were performed. According to WHO recommendations, wide application Metamizole is not recommended in pediatric practice due to the presence of severe complications (special letter dated October 18, 1991). Recently, in Russia there has also been a ban on the use of acetylsalicylic acid in children under 15 years of age. Thus, it became necessary to use other antipyretics in the sample.

We chose NUROFEN FOR CHILDREN as a test for the presence of thermoregulation disorders of central origin ( active substance- ibuprofen, manufacturer - RECKITT BENCKISER, UK). The drug is usually well tolerated without causing gastric irritation, which is considered its main advantage over salicylates. The mechanism of action of ibuprofen is due to inhibition of the biosynthesis of prostaglandins - mediators of pain and inflammation. It is known that the drug blocks prostaglandins not only in the hypothalamus, but also in all organs, which causes good antipyretic, analgesic and anti-inflammatory effects. NUROFEN FOR CHILDREN is used in children in a single dose of 5 to 10 mg/kg body, it begins to act within minutes after administration, peak effectiveness is after 2-3 hours.

A test with Analgin was carried out on 15 children (age 11-15 years), of which 10 were girls and 5 were boys. The test with NUROFEN FOR CHILDREN was used in 13 children (age 6-15 years), of which 5 were girls and 8 were boys. Thus, the number of children, age, sex composition and nosology in the groups did not differ significantly. The test procedure remained standard. To monitor the condition, a temperature sheet was attached to the medical history.

All indicators were recorded over several days, including the day of taking NUROFEN FOR CHILDREN. Children received the drug in age dosage 4 times a day (8:00 -16:00). Tolerability of NUROFEN FOR CHILDREN was good in the vast majority of patients (Table 2). Not a single child showed poor tolerability of the drug.

Table 2. Tolerability of the Nurofen test

The incidence of side effects was compared in two groups: children who underwent a classic analgin test, and patients who received NUROFEN FOR CHILDREN (Table 3).

Table 3. Frequency of side effects when comparing analgin and nurofen tests

The obtained result of the comparison of Analgin/Nurofen for children showed better tolerability of the test using NUROFEN FOR CHILDREN. In the group of patients who underwent an analgin test, almost half of the children experienced side effects, while in patients who received NUROFEN FOR CHILDREN - only 8%. In addition, in children who underwent a nurofen test, there were no significant changes in the control blood test.

Thus, this study showed the need to take into account the factor of impaired thermoregulation of central origin in the differential diagnosis of LNG in children. The use of a diagnostic test with NUROFEN FOR CHILDREN (RECKITT BENCKISER) made it possible to obtain convincing evidence dysfunctional thermoregulation disorders with good tolerability of the drug with a minimum number of side effects.

The list of used literature is in the editorial office.

Lyudmila Ivanovna Vasechkina, senior researcher at the pediatric department of the Moscow Regional Research Clinical Institute named after. M.F. Vladimirsky, Ph.D. honey. Science Tamara

Konstantinovna Tyurina, senior researcher at the pediatric department of the Moscow Regional Research Clinical Institute named after. M.F. Vladimirsky, Ph.D. honey. sciences

Temperature of central genesis

My 16-year-old son has a brain cyst, episyndrome. and in recent days the so-called hyperthermia of central origin. Temperature is over 40. Analgin and all kinds of suppositories do not help. Nurofen too temperature from 40.1 to 40.4. all pale. doesn't even sweat. the neurosurgeon with whom we are seeing and maybe We will undergo surgery and advised us to go to Botkinskaya. but for a number of reasons we cannot do this now. and my son is hardly transportable now.

We want to contact a knowledgeable neurologist and have her examined. and/or correct the so-called conservative therapy, cat. My wife and I (not doctors) prescribed it with the help of a neurosurgeon.

who to contact. maybe there is someone here from the Botkin hospital here. Or just a knowledgeable neurologist somewhere. please advise.

The fact is that this so-called “diagnosis” is a given. and not set by us. the phrase came across when he was sent to a hospital (I don’t have the documents at hand - I can’t say who and where now). I understand that this is not honey at all. diagnosis in the sense of cat. this word is commonly used.

please tell me what information you need? Well, to rule out the infectious nature of the fever. course: white fever. no vomit. and the temperature remains high with NG (38-39). the last few days - such an increase - up to 40.4.

and as for call 03, the guy will be put into infectious diseases or therapy - at best - and I really wouldn’t want that. for a number of reasons. He also has a whole “bouquet” of diseases (asthma, heart, kidneys). and this is a real threat to life. IMHO.

If you need any more information, I will certainly provide it.

sorry for the confusion. thanks for the prompt response.

Yes, it completely popped out. - the guy also has thyroid problems

Is New Year a New Year? During this time, were any tests done?

Your son probably has fever of unknown origin (FUO). To clarify its nature, it is enough to answer questions online. There is a specific examination algorithm for LNG, starting with malaria and ending with autoimmune diseases. As a rule, this is done on an inpatient basis, possibly in the therapeutic department (but, in any case, after consulting an infectious disease specialist).

There are drug fevers (for example, due to antiepileptic drugs and even to the analgesics-antipyretics themselves).

To exclude artificial (including artificially induced) fever, check whether your son has a fever (with your palm), measure the temperature with two thermometers and in the mouth.

Comments to the post:

Where can I go with my illness?

Increased body temperature in children with developmental disabilities: available methods and medications

An increase in body temperature in any child is a consequence of some pathological process, mainly infectious, which led to the development of such a protective reaction of the body.

An increase in body temperature (hyperthermia) is precisely the body’s protective reaction when an infectious agent is introduced. In this state the speed increases biochemical processes, synthesized large number biologically active substances whose action is aimed at destroying bacteria, viruses or other foreign bodies inside the body.

However, such a defensive reaction can cause serious complications and even death of the patient, so in this situation, if you do not have special medical skills and knowledge, you should not self-medicate, since elevated temperature accompanies a wide variety of pathological conditions that can cause irreparable harm to the health of a child with special needs psychophysical development, and an ordinary healthy child.

For example, an elevated temperature in a child with convulsive seizures or epilepsy can provoke this attack at the peak of its activity, and in these conditions the attack in most cases will be quite severe and will often turn into status epilepticus, which is not controlled by the main means of first aid. emergency medical care.

Causes of increased body temperature in a child with psychophysical characteristics

In children with special needs of psychophysical development, hyperthermia is observed when:

• infectious processes caused by bacteria and viruses;
• violations of thermoregulation due to serious damage to the nervous system;
• manifestation of excessive emotionality, mental agitation.

It is obvious that tactics to eliminate hyperthermia in different cases will also vary.

Hyperthermia in an infectious disease

If your special child's body temperature rises to high levels, your actions will be as follows. Firstly, you must clearly know how your child reacts to this hyperthermia, that is, whether the state of hyperthermia occurs with redness and an increase in the temperature of the skin, or whether the skin of the hands and feet, on the contrary, becomes white and cold. It is also necessary to remember about convulsive syndrome, if your child has a history of one. In addition, it is definitely worth remembering how the temperature behaves: it rises or falls sharply, or slowly.

However, not all parents may be capable of such an analysis, not because they are far from medicine, but because this is simply the first time this has happened to them. If this situation happens to you for the first time, be sure to call a doctor or emergency medical services, since only they can provide adequate assistance.

To understand why the temperature has risen, it is worth looking at the child and the presence of possible symptoms. Symptoms that may immediately appear include:

• runny nose;
• redness of the eyes;
• lacrimation;
• coughing;
• acceleration of the pulse by 10 beats for each degree above normal.

These signs may suggest that your special child has developed an infection. What kind of infection it is is another question, because often with both viral and bacterial infections the body temperature can be the same.

In case of an infectious disease, an increase in body temperature in children may be due to general intoxication of the body caused by the activity of microorganisms. Thus, simply lowering the temperature will not lead to recovery, but will simply eliminate unpleasant symptom. There are two sides to the coin here. One side is the positive role of hyperthermia in the destruction of infectious agents, and the other side is the negative impact of hyperthermia on the altered organism of a child with characteristics of psychophysical development. Precisely because the negative component is quite serious and significant, body temperature should be reduced to normal numbers.

How to reduce the temperature during an infectious disease?

Of course, you need to influence the cause. If the disease is of viral etiology, antiviral drugs are prescribed; if it is bacterial, antibiotics are prescribed.

You can directly lower the temperature using a physical method, that is, uncover the child so that he cools down naturally, or wipe him with a cloth moistened with ordinary water, which is 10 C lower than body temperature. For example, if hyperthermia is 39C, then the water temperature cannot be lower than 29C. In addition, there are methods using a vinegar solution, as well as a semi-alcohol solution, to wipe or wet the skin.

Please note that wiping and wetting are two fundamentally different aspects. If wiping is used in cases where the child’s hands and feet are pale and cold during hyperthermia, then wetting the skin is used for “red” hyperthermia, when the skin is red and hot.

In the absence of any effect from the physical method of reducing body temperature, medications are used. You should try medications first internal use, that is, tablets, suspensions, syrups, suppositories. Mainly used for children:

• paracetamol, although its safety is currently under debate;
• ibuprofen, which is considered the most suitable means to reduce fever in children;
• combination drugs containing paracetamol and ibuprofen. Their efficiency increases significantly.

Children with special psychophysical development problems have problems taking oral (by mouth) medications. Some don’t want to, some can’t, some are cunning and don’t swallow and then spit it out secretly from their parents; for some, these drugs don’t help or are not fast enough.

The speed of action of the drug is important in cases where a child experiences convulsions during hyperthermia that can kill.

To make the medicine work faster, use parenteral drugs. These are mainly analgin, papaverine and diphenhydramine. Instead of diphenhydramine, chlorpromazine can be used in hospitals. These three drugs are administered simultaneously in one syringe at a dosage of 0.1 ml/year of life and are popularly called the “triad”.

We remind you once again that lowering body temperature is not a procedure that eliminates the problem, therefore, in case of an infectious disease in a child with special psychophysical development, consultation with a specialist is necessary.

How to reduce temperature if thermoregulation is impaired?

With an increase in body temperature of central origin, that is, caused not by an infection, but by some damage in the brain, there is no increase in heart rate, so the origin of hyperthermia can be distinguished quite clearly. However, if you do not have theoretical and practical medical information, you should not experiment and guess, since anything can happen in medicine. Your child may have a central rise in body temperature and at the same time develop a complex infectious disease.

Reduce body temperature of central origin with psychotropic drugs, antidepressants, and antispasmodics. These drugs can also be used for hyperthermia after the manifestation of excessive emotionality and mental arousal.

Disturbances in thermoregulation in children with special needs of psychophysical development are not uncommon and, once they appear, they almost never go away. In such children it is difficult to distinguish the origin of hyperthermia. This requires examinations and monitoring of the patient’s condition.

What antipyretic techniques do we use in practice?

Basically, we immediately use antipyretic tablets or suppositories at a body temperature of 38C and above. If they are ineffective, we introduce the “troika” within minutes. This is in children without convulsive syndrome and without the risk of developing a convulsive syndrome against the background of high body temperature, although “without risk” is a relative concept, since each of the children with special needs of psychophysical development has a risk, in varying degrees, development of convulsive syndrome.

In children with a history of convulsive syndrome and its development during hyperthermia, we immediately use the injection method - administering a mixture of analgin, papaverine, and diphenhydramine in the required proportions. Usually we do not wait for the temperature to rise to 38C, but give the injection within the temperature range of 37.2 - 37.5C.

If these methods are ineffective, physical methods of reducing body temperature are used.

In parallel with antipyretics, antiviral or antibacterial drugs are prescribed, depending on the symptoms and the presumed origin of the infection.

In conclusion

It is not possible in one article to describe and talk about everything that exists and about all the cases that have occurred and are occurring in practice. We are always waiting for your questions, comments and are open to conversation and help.

If, in the absence of other painful symptoms, the temperature suddenly rises and persists for a long period, there is a suspicion that this is fever of unknown origin (FOU). It can occur in both adults and children with other diseases.

Causes of fever

In fact, fever is nothing more than protective function the body, which is “involved” in the fight against active bacteria or other pathogens. Speaking in simple language, due to the increase in temperature, they are destroyed. Related to this is the recommendation not to lower the temperature with pills if it does not exceed 38 degrees, in order to allow the body to cope with the problem on its own.
The characteristic causes of LNG are severe systemic infectious diseases:

• tuberculosis;
• salmonella infection;
• brucellosis;
• borelliosis;
• tularemia;
• syphilis (see also -);
• leptospirosis;
• malaria;
• toxoplasma;
• AIDS;
• sepsis.

Among the localized diseases that cause fever are:

• blood vessel thrombi;
• abscess;
• hepatitis;
• damage to the genitourinary system;
• osteomyelitis;
• dental infections.

Symptoms of a febrile state

The main signal of this disease is elevated body temperature, which can last up to 14 days. Along with this, symptoms characteristic of patients of any age appear:

• lack of appetite;
• weakness, fatigue;
• increased sweating;
• chills;

These symptoms are general in nature, they are common to most other diseases. Therefore, it is necessary to pay attention to such nuances as the presence of chronic diseases, reactions to medications, and contact with animals.

Symptoms "pink" And "pale" fevers differ in clinical features. At the first sight of fever in an adult or child, the skin normal color, slightly damp and warm - this condition is considered not very dangerous and passes easily. If the skin is dry, vomiting, shortness of breath and diarrhea appear, the alarm should be sounded to prevent excessive dehydration.

"Pale" fever is accompanied by marbled pallor and dry skin, blue lips. The extremities of the arms and legs also become cold, and heartbeat irregularities occur. Such signs indicate a severe form of the disease and require immediate medical intervention.

When the body does not respond to antipyretic drugs and the body temperature goes off scale, dysfunction of important organs may occur. Scientifically, this condition is called hyperthermic syndrome.

With “pale” fever, emergency comprehensive medical care is necessary, otherwise irreversible processes may begin, which sometimes lead to death.

If a newborn has a fever of more than 38 degrees, or a child over one year old has a fever of 38.6 or higher, you should immediately consult a doctor. The same must be done if an adult has a fever of up to 40 degrees.

Classification of the disease

During the study, medical researchers identified two main types of LNG: infectious And non-infectious.

The first type is characterized by the following factors:

• immune (allergies, connective tissue diseases);
• central (problems with the central nervous system);
• psychogenic (neurotic and psychophysical disorders);
• reflex (feeling of severe pain);
• endocrine (metabolic disorders);
• resorption (incision, bruise, tissue necrosis);
• medicinal;
• hereditary.

A febrile state with an increase in temperature of non-infectious etymology appears as a result of central or peripheral exposure to leukocyte breakdown products (endogenous pyrogens).

Fever is also classified according to temperature indicators:

• subfebrile - from 37.2 to 38 degrees;
• febrile low – from 38.1 to 39 degrees;
• febrile high – from 39.1 to 40 degrees;
• excessive - more than 40 degrees.

By duration There are different types of fever:

• ephemeral – from several hours to 3 days;
• acute – up to 14-15 days;
• subacute – up to 44-45 days;
• chronic – 45 or more days.

Survey methods

The attending physician sets himself the task of determining which types of bacteria or viruses turned out to be the causative agent of fever of unknown origin. Premature newborns up to six months of age, as well as adults with a weakened body due to a chronic disease or other reasons listed above, are especially susceptible to their effects.

To clarify the diagnosis, a series of laboratory research:

• general blood test to determine the content of platelets, leukocytes, ESR;
• urine analysis for the content of leukocytes;
• biochemical blood test;
• bacterial cultures of blood, urine, feces, mucus from the larynx from cough.

In addition, in some cases, bacterioscopy to exclude suspicion of malaria. Also, sometimes the patient is offered to undergo a comprehensive examination for tuberculosis, AIDS and other infectious diseases.

Fever of unknown origin is so difficult to diagnose that it is impossible to do without examinations using special medical equipment. The patient undergoes:

• tomography;
• skeletal scan;
• X-ray;
• echocardiography;
• colonoscopy;
• bone marrow puncture;
• biopsy of liver, muscle tissue and lymph nodes.

The range of all diagnostic methods and tools is quite wide; on their basis, the doctor develops a specific treatment algorithm for each patient. It takes into account the presence of obvious symptoms:

• joint pain;
• change in hemoglobin level;
• inflammation of the lymph nodes;
• the appearance of pain in the area of ​​internal organs.

In this case, the doctor has the opportunity to move more purposefully towards establishing an accurate diagnosis.

Features of treatment

Despite the fact that fever of unknown origin poses a danger not only to health, but also to human life, one should not rush to take medications. Although some doctors prescribe antibiotics and carticosteroids long before determining the final diagnosis, citing the goal of alleviating the patient’s physical condition as soon as possible. However, this approach does not allow making the right decision for more effective treatment. If the body is under the influence of antibiotics, it becomes more difficult in the laboratory to find the true cause of the fever.

According to most doctors, it is necessary to conduct further examination of the patient, using only symptomatic therapy. It is carried out without prescribing potent drugs that blur the clinical picture.

If the patient continues high fever, he is advised to drink plenty of fluids. The diet excludes foods that cause allergies.

If you suspect infectious manifestations, he is placed in an isolated ward of a medical institution.

Treatment with medications is carried out after detection of the disease that caused the fever. If the etiology (cause of the disease) of fever has not been established after all diagnostic procedures, the use of antipyretics and antibiotics is allowed.

• under 2 years of age with a temperature above 38 degrees;
• at any age after 2 years – over 40 degrees;
• who have febrile seizures;
• who have central nervous system diseases;
• with dysfunctions of the circulatory system;
• with obstructive syndrome;
• with hereditary diseases.

Which doctor should I contact?

If an adult exhibits obvious symptoms LNG, he should contact infectious disease specialist. Although most often people turn to therapist. But if he notices the slightest suspicion of fever, he will certainly refer you to an infectious disease specialist.

Many parents are interested in which doctors should be contacted at the first symptoms of the disease in question in children. First of all, to pediatrician. After the preliminary stage of examination, the doctor refers the small patient to one or more specialized specialists: cardiologist, infectious disease specialist, allergist, endocrinologist, virologist, nephrologist, otolaryngologist, neurologist.

Each of these doctors takes part in studying the patient's condition. If it is possible to determine the development of a concomitant disease, for example, associated with allergic reaction for food or medicine, an allergist will help here.

Drug treatment

For each patient, the doctor develops individual program taking medications. The specialist takes into account the condition against which the disease develops, determines the degree of hyperthermia, classifies the type of fever and prescribes medications.

According to doctors, medications are not assigned at "pink" fever with an unburdened background (maximum temperature 39 degrees). If the patient does not have serious illnesses, his condition and behavior are adequate, it is recommended to limit himself to drinking plenty of fluids and using methods of cooling the body.

If the patient is at risk and has "pale" fever, he is assigned Paracetamol or Ibuprofen . These drugs meet the criteria for therapeutic safety and effectiveness.

According to WHO, Aspirin refers to antipyretics that are not used to treat children under 12 years of age. If the patient cannot tolerate Paracetamol and Ibuprofen, he is prescribed Metamizole .

Doctors recommend taking Ibuprofen and Paracetamol at the same time, according to a developed regimen individually for each patient. At combined use The dosage of such medications is minimal, but it gives a much greater effect.

There is a drug Ibuklin , one tablet of which contains the low-dose components of paracetamol (125 mg) and ibuprofen (100 mg). This drug has a rapid and prolonged effect. Children should take:

• from 3 to 6 years (body weight 14-21 kg) 3 tablets;
• from 6 to 12 years (22-41 kg) 5-6 tablets every 4 hours;
• over 12 years old – 1 tablet.

Adults are prescribed a dosage depending on age, body weight and physical condition of the body (presence of other diseases).
Antibiotics selected by the doctor in accordance with the test results:

• antipyretics (Paracetamol, Indomethacin, Naproxen);
• Stage 1 of taking antibiotics (Gentamicin, Ceftazidime, Azlin);
• Stage 2 – prescription of stronger antibiotics (Cefazolin, Amphotericin, Fluconazole).

Folk recipes

On this hour Traditional medicine offers a huge selection of remedies for every case. Let's look at some recipes that help alleviate the condition of fever of unknown origin.

Lesser periwinkle decoction: Pour 1 tablespoon of dry leaves into a vessel with a glass of water and boil for 20-25 minutes. After an hour, strain and the broth is ready. You should drink the entire volume per day in 3 doses.

Tench fish. Dried fish gall bladder must be ground into powder. Take 1 bottle per day with water.

willow bark. Pour 1 teaspoon of bark into the brewing container, after crushing it, pour in 300 ml of water. Boil, reducing heat to low, until about 50 ml has evaporated. It should be taken on an empty stomach; you can add a little honey to the decoction. You must continue drinking until complete recovery.

LNG is one of the diseases the treatment of which is very difficult due to the difficulty of determining the causes of its occurrence, so you should not use folk remedies without the permission of the attending physician.

Preventive measures for children and adults

To prevent a feverish state, basic health care is necessary in the form of regular medical examination. In this way, timely detection of all kinds of pathologies can be guaranteed. The earlier the diagnosis of a particular disease is established, the more favorable the treatment outcome will be. After all, it is a complication of an advanced disease that most often causes fever of unknown origin.

There are rules that, if followed, will reduce the likelihood of LNG in children to zero:

• do not contact with infectious patients;
• receive a complete balanced diet;
• physical activity;
• vaccination;
• maintaining personal hygiene.

All these recommendations are also acceptable for adults with a small addition:

• exclude casual sexual relationships;
• use barrier contraception methods in intimate life;
• When staying abroad, do not eat unknown foods.

Infectious disease specialist about LNG (video)

In this video, an infectious disease doctor will talk about the causes of fever, its types, methods of diagnosis and treatment from his point of view.

An important point is heredity and the body’s predisposition to certain diseases. After a thorough comprehensive examination, the doctor will be able to make the correct diagnosis and prescribe an effective therapeutic course to eliminate the causes of fever.

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