Prolonged fever

We deal here that prolonged unexplained fevers. The diagnostic approach to acute fever is bad schématisable effect.

It depends too associated symptoms, and would amount to treat each other of all infectious diseases.

Although the possible causes prolonged fever are multiple, the diagnostic process is fairly stereotypical:

– Ensure that it is a fever;

– Know the few diagnostic hypotheses to spread rapidly;

– Know the three major etiologic groups of prolonged fever;

– Make a precise examination and clinical examination (very important);

– Undertake further tests (usually in two successive waves).


Unexplained prolonged fever is classically defined as a temperature higher than 38.3 ° C, recorded several times for 3 weeks and whose etiology is not found after a “clinical and paraclinical investigation routine” (complete clinical examination, chest X-ray, blood counts liver tests, urine culture [urine culture]).

This definition may in our opinion be expanded to a higher unexplained temperature at or above 38 ° C, lasting for a little less time.

To consider physiological shifts of temperature (second part of the cycle and pregnancy), responsible for a thermal shift, however not exceeding 38 ° C.

There must be, in borderline cases to the examination of a temperature curve:

– From the morning (wake) to night (after 15 min rest in supine position);

– Including shiver or sweat thrust.

Main causes:

The diagnostic approach to be adopted before a prolonged fever is dictated by the knowledge of the main etiologies (Table I):

– Infections;

– you die ;

– Inflammation.

A fourth group “catch-all” concerns very diverse pathologies.


It is summarized in the decision tree (Fig. 1). The investigation must discover as quickly as possible a curable etiology.

The examination and clinical examination occupy an essential place.


The data to be collected on the patient’s field are:

– Ethnicity and family history, which can move towards a periodic disease, autoimmune diseases, etc. ;

– Personal history: tuberculosis (specifying the date of infection: before or after the arrival of TB on the market [streptomycin; 1948 isoniazid: 1952; rifampicin: 1968]), tumors, allergies, heart valve history, care dental interventions, prosthetics (joints, heart valves, vascular), pacemaker, transfusions;

– Vaccination status;

– Lifestyle (drug abuse, smoking, risky sexual behavior, etc.).

Data regarding the patient’s environment are:

– Recent stay abroad (malaria, amoebiasis, typhoid, hepatitis, etc.);

– Professional activities (inhalations, health profession, etc.) And leisure [river baths (spirochétose), gardening, hunting, forest walks (Lyme disease)];

– Seafood consumption (hepatitis, salmonellosis), cheese or farm milk (brucellosis, listeriosis);

– Presence of animals in the immediate environment, bites and stings possible (psittacosis, rickettsial disease, Lyme disease, hydatid disease, leishmaniasis);

– Entourage diseases (tuberculosis, hepatitis);

– Wounds, bites.

The examination should list the treatments, not to mention those who are not regarded as such by the patient (contraception, hormone replacement therapy, eye drops, syrups, etc.)

and drugs administered since the onset of fever (antibiotics, anti-inflammatories, corticoids).

The characteristics of the fever should be noted, however, without giving them excessive value. A brutal installation mode instead evoke an infectious disease, a short-term periodicity malaria, longer-term periodicity genetic periodic fever (FMF for example), a character waving lymphoma.

Possible associated manifestations are: chills (though not specific to an infectious disease), sweating (lymphoma, tuberculosis, brucellosis), not spontaneously reported pain (jaw claudication). It will carefully search fleeting symptoms like rash (Still’s disease), purpura, false paronychia (endocarditis).

Physical examination:

In this context, the clinical examination must naturally be complete. We must pay particular attention to:

– Examination of the skin purpura purpura or traces on the ankles (vasculitis, endocarditis), even fleeting rash (Still’s disease), including in the folds (rickettsial);

– Abdominal palpation: with among others, examination of the external genitalia (tuberculous epididymitis, cancers), pelvic examination (rectal cancer or ovarian cancer, prostatitis) and search for splenomegaly (infections, lymphoma);

– Palpation of the thyroid in search of goiter, nodule or pain (hyperthyroidism, cancer, thyroiditis);

– Palpation of breasts;

– Looking for axillary lymph nodes without forgetting areas (lymphoma or tuberculosis can not be by one lymphadenopathy)

– Cardiac auscultation: it must be especially careful in search of a diastolic murmur of aortic insuffi dence more difficult to perceive a systolic murmur (endocarditis, aortic dissection);

– Palpation (Takayasu) and auscultation (aneurysms) of arteries without forgetting the temporal arteries (arteritis);

– Dissociation between pulse and temperature (typhoid fever, brucellosis, artificial fever);

– Dental condition and the mouth (thrush, sarcoma AIDS, etc.).

First series of additional tests:

If the fever is high or poorly tolerated, it will hospitalize the patient.

Otherwise, in the absence of motivating policy elements directed clinical investigations, an outpatient we practice a first series of biological and radiological additional tests (Fig. 1).

After this first analysis, sometimes we can already diagnose or have an orientation:

Drug fever typically installs a week after the start of treatment, but the delay is actually quite variable. It can take all types, including high fever with chills. The absence of allergic manifestations associated (pruritus, urticaria, eosinophilia) does not eliminate this hypothesis.

The treatment is the discontinuation of the drug responsible for the fever, which usually disappears after a few days; it is most often antibiotics (especially penicillins, cephalosporins, trimethoprim-sulfamethoxazole), methyldopa,

quinidine, etc. The list is very long, and it will refer to the listed side effects of various medications taken by the patient.

A frequently encountered case is taking progestins, either as part of a replacement therapy for menopause or perimenopause, or at a birth. Synthetic progestins totaled almost all “physiologically” the temperature a few tenths of a degree, without exceeding 38 ° C, when the temperature is taken at rest.

Often the thermal offset is found at the waning of an acute infectious episode; we will check the normality of the ESR (erythrocyte sedimentation rate) away from this episode. Because of the prolonged effect of these progestins their arrest, as a test, followed by a thermal decay often very slow but may require up to a month for certain derivatives.

The dummy fever should be considered before a strong fever, prolonged, not causing tachycardia, paradoxically well tolerated and for which descrambling examinations, especially VS, are normal. It usually affects women working in paramedical. The diagnosis is not always easy and can be helped by concomitant urinary temperature or visual check of the temperature taken.But sometimes these fevers are related to a autoprovoqué sepsis, indicating a more serious psychopathological disorder (Munchausen syndrome).

Vocational fever is often due to polymer vapor inhalations or various metals (copper, zinc, nickel, aluminum).

Upon discovery of HIV status, the reasoning is particularly based on etiology: tumor (lymphoma) and especially infectious (pneumocystis pneumonia, tuberculosis, CMV [cytomegalovirus], etc.) Specific to this type of immunosuppression. Table II summarizes the main diseases to raise with prolonged fever in the number of lymphocytes

CD4. In fact, very often in this case, hospitalization is required.

Second series of additional tests:

If a track does not appear, it will then use a second series of additional tests that can be performed on an outpatient or inpatient grouped starting with the least aggressive.

The thoraco-abdominopelvic CT examination is a very profitable because it helps guide the diagnosis in about 30% prolonged fever.

It can indeed detect infections (deep lymph nodes of tuberculosis, localized abscesses potentially infected aneurysms) and tumor (kidney cancer and other cancers, metastasis, lymph node lymphoma).

Echocardiography will perform early if there is a breath on auscultation; examination of 2nd intention, it is systematic.

When in doubt about endocarditis, there is an indication to direct the hospital patient as repeated blood cultures are very difficult to externally and treatment should be done at the earliest (see Table III in the treatment part). In general, for not “negate” blood cultures, it is desirable not to take antibiotic treatment to the blind and externally.

When in doubt, we can make practice a venous Doppler of the lower extremities and the vena cava or pulmonary scintigraphy as deep vein thrombosis, especially the vena cava (often visible to the scanner) or pelvic veins can cause an intensity lasting fever usually mild but sometimes exceeds 38.5 ° C.

The biopsy of the temporal arteries, which can often be done on an outpatient system should be done in search of Horton’s disease in a patient over 60 years with prolonged fever and inflammation, even in the absence of cephalic signs, if the first round of reviews and the scanner is not moving towards a diagnosis because it is a potentially disabling disease brutally (blindness) and easily curable.

Hospital stage 3rd series of additional tests:

In the absence of diagnosis, further investigation will be done in a hospital.

After resumption of questioning and clinical examination (to be able to change since the beginning of the fever), some blood tests will be redone, blood cultures will be more easily achieved and externally, infectious disease serology more rarely encountered will be made.

Patients usually undergo a bone marrow biopsy (with marrow culture) sometimes used to establish diagnosis (lymphoma, tuberculosis forming organs, leishmaniasis), and elsewhere guide (intramedullary granuloma).

Other reviews will be considered case by case:

– Digestive endoscopy;

– Bronchoscopy, with or without lavage;

– Liver biopsy;

– Transesophageal echocardiography.

Perhaps the PET scan will change in the years ahead the diagnostic process. His place in the study of prolonged fever is being evaluated.


Prolonged fever after returning from a tropical country:

Inflammatory and tumor causes are the same as those cited in the general case.

Note only that sun exposure can promote lupus flare.

Regarding the infectious etiologies are rare infections presenting with isolated fever:

Parasites: we must first eliminate malaria starting with a blood smear.

However, two months after returning from tropical countries, falciparum malaria was very unlikely to be involved.

Viruses: besides HIV, hepatitis in preicteric phase is possible, flaviviruses and Hanta virus rarely occur in an isolated fever;

Bacterial infections: beware of salmonellosis because the digestive signs may be in the background or non-existent.

Periodic fever:

This is febrile, iterative, separated by days or weeks of apyrexia.

Almost all etiologies above-mentioned within the general framework may be involved, but some will be more possible:

Infectious causes: malaria is likely

too often incriminated in patients who stayed abroad. It is recalled that after two months after returning from endemic countries, falciparum malaria is exceptional; it may be of revival of Plasmodium vivax or oval (but only up to 5 years after the return) or P. malariae (for several years).

However, root canal bacterial infections, urinary or biliary, are much more common in temperate climates;

Tumor causes lymphomas;

Medicinal causes with iterative medications: they will be searched by interrogation (eg synthetic progestins);

Series of hereditary recurrent inflammatory diseases responsible for recurrent fever is the most common recurrent disease or familial Mediterranean fever; others are more rare: Hyper IgD, TRAPS (TNFRSFA1- associated periodic syndrome), Muckle-Wells.

They all begin in childhood or adolescence, and generally have a family character.

Their diagnosis is based on genetic tests or more specialized assays. Suspected such rare condition, referral to a specialist in internal medicine is desirable.

FEVER LASTING unexplained:

After this investigation, in 5-30% of cases, the cause of prolonged fever remains a mystery.

If the clinical situation is not alarming, it is sometimes possible to interrupt the investigations then maintaining clinical monitoring pending a semiotic element again. In almost 70% of cases, spontaneous surrender of the fever is then noted, usually within a few weeks, especially in young patients. A presumptive diagnosis of benign viral infection will be retained.

Moreover, the fever persists and sounds of the general condition. A test treatment is possible, in hospitals, in some situations:

– Heparin, if thromboembolic disease is suspected; test penicillin antibiotic aminoglycosides or vancomycin-aminoglycoside at a valvulopathe, in the event of endocarditis with negative blood cultures (Table III);

– TB test treatment indications should be wide, particularly in patients at risk (elderly, immigrants, immunocompromised, inadequately treated TB history) and / or before a feverish granulomatosis (see Box 1);corticosteroids, when an inflammatory disease is suspected, especially vasculitis or arteritis not confirmed histologically. However, the thermal fall recorded corticosteroid is not specific.

Box 1. Treatment of tuberculosis
Principles of Treatment
This treatment is based on a combination of antibiotics inoculated in 2 steps:
– 4 TB association for a period of 2 months (reduction of the bacterial inoculum);
– 4 TB association whose duration depends on the site of infection and the existence of immunosuppression (eradication of infection).
Treatment modalities
• Four molecules of antibiotics are routinely used in the following dosages:
– Isoniazid (3-5 mg / kg) and rifampicin (10 mg / kg to be taken on an empty stomach) (throughout the process);
– Ethambutol (15 mg / kg) and pyrazinamide (20 mg / kg) (for the first 2 months). Some teams reserve ethambutol with MDR-TB, particularly those that occur during HIV infection.
The duration of antibiotic treatment is:
– Pulmonary tuberculosis: 6 months in total;
– Glandular tuberculosis: 9 months in total;
– Bone or meningeal tuberculosis: 12 months in total;
– In case of co-infection with HIV: minimum 9 months.
The most common pattern is taking all the tablets at once, fasting, 2 hours before the first meal of the day.However, only rifampicin requires a fasting state, and other antibiotics can be distributed on the day in case of poor digestive tolerance.
• Corticosteroid therapy at a dose of 1.3 mg / kg is routinely indicated in the following locations: neuromeningeal and pericardial. It can be noted in other locations depending on the seriousness of the infringement.
Toxicity Treatment
The toxicity of the treatment is:
– Liver toxicity (most common): pyrazinamide, isoniazid and rifampicin;
– Toxicity on peripheral nerves: isoniazid;
– Ophthalmological toxicity (retrobulbar optic neuritis)
: Ethambutol and isoniazid above;
– Rare toxicities: rifampicin may cause interstitial nephritis, cytopenia, hemolytic anemia, drug eruption, fever, etc. These events are the result of hypersensitivity, and are favored by batch processing or prior exposure.More rarely, isoniazid may induce lupus, hypersensitivity disorders, shoulder hand syndrome, acne, or more or less severe psychiatric disorders ranging from insomnia to serious delusional disorders;
– Constant and mild side effects: red coloration in biological fluids by rifampicin, the patient should be warned;hyperuricemia due to the metabolism of pyrazinamide (exceptionally symptomatic).
enzyme induction
Rifampicin is a potent enzyme inducer reducing serum and effi ciency of many associated treatments. Any association must be verifi ed. 2 include frequent special cases with potentially serious consequences: inactivation of oral contraception and decreased effi ciency of antiretroviral therapy. The steroid dose (1.3 mg / kg) recommended in tuberculosis is thus equivalent to 1 mg / kg.
Consultations take place at D0, D15, M1, M2, and then every 2 months until the end of treatment.Ophthalmologic consultation is recommended with color vision and fundus at D0.
In biology, pretherapeutic includes: transaminases, NFS [blood count] platelets, urea, creatinine, serum electrolytes, TP-TCK. Transaminases are assayed at D0, D15, M1 and M2 then every 2 months until the end of treatment.
In cases of pulmonary tuberculosis, a chest X-ray is performed at D0, D15, M3 and M6. If initial positive sputum, a research BK is conducted monthly to negativity.
In case of complicated tuberculosis or coinfection with HIV, these tests may be more common. The use of more sophisticated radiological tests (ultrasound, CT, MRI, etc.), serum assays due to drug interactions or a different treatment regimen may be necessary. The support must be in a specialized environment.


The exploration of unexplained prolonged fever is easily schématisable. Much of these can be done by the general practitioner. But when the survey comes up after the first two series of additional tests or if the patient’s condition is worrying, working closely with a hospital is necessary.