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Tuesday, April 14, 2020

Prolonged Fever: 07 Essential steps to reach the diagnosis? Blind empirical drug therapy when indicated?

Prolonged Fever


STEP # 01: Keep in mind the causes of prolonged fever

These are infections & non-infectious causes

Infections causes:

Bacterial infections 
Systemic infections: Salmonellosis, brucellosis, listeriosis, leptospirosis, tularemia, tuberculosis 
Hidden focal infections: Abscess (liver, perinephric, pelvic), endocarditis, pericarditis, pyelonephritis, osteomyelitis 

Viral infections 
Infectious mononucleosis, cytomegalovirus infection, Human immunodeficiency virus (HIV), hepatitis 

Parasitic infestations 
Malaria, toxoplasmosis, visceral larva migrans

Non-infectious causes:

Rheumatic diseases
Rheumatic fever, systemic rheumatoid arthritis, polyarteritis nodosa, systemic lupus erythematosus, kawasaki disease, mixed connective tissue disease

Malignancies
Leukemia, lymphoma, neuroblastoma

Immune reactions
Drug fever, serum sickness

Other causes
Factitious fever or false fever, Crohn disease, Diabetes insipidus, Anhydrotic ectodermal dysplasia, Familial Mediterranean fever

STEP # 02: Is it  prolonged fever?

Prolonged fever is a fever with duration of more than 10 - 14 days. Although it is not as common as short febrile illness, it causes greater concern of both parents and doctors.
Fortunately, unlike adults, most cases of prolonged fever in children are caused by benign infections and the prognosis for ultimate recovery is generally good.

STEP # 03: Is it  true prolonged fever?

Is it truly a prolonged fever?
• Is there an evident cause?
• Unexplained prolonged fever... What is the cause?

Is it truly a prolonged fever?
The complaint of prolonged fever, as any other prolonged complaint, should not be accepted without careful analysis. Parents may misinterpret normal temperature as a mild fever. Careful history may reveal that the condition represents 2 short febrile illnesses rather than a prolonged one. Documentation of fever is important in accepting the complaint as a true prolonged fever.

STEP # 04: Is there an evident cause for prolonged fever?

With documented prolonged fever, detailed history and meticulous examination may
reveal an evident cause or at least suggest a specific disease.

History and examination in children with prolonged fever

Nonspecific findings denoting significant illness

Symptoms: Anorexia, weight loss.
Signs: Toxic look, pallor, cachexia, lymphadenopathy or Hepatosplenomegaly.

Specific findings suggesting a particular disease

Symptoms related to a specific system: CNS, chest, heart, GIT, urinary.

History of contact to an adult with chronic chest disease: ? Tuberculosis.

History of eating rabbit meat: ? Tularemia.

History of medications: ? Drug fever.

Rigors: Septicemia, pyelonephritis or malaria.

Pharyngitis: Infectious mononucleosis, cytomeglovirus, tularemia, toxoplasmosis.

CNS examination May suggest meningitis.

Chest examination: May reveal pneumonia or empyema.

Cardiac examination: May reveal endocarditis or pericarditis.

Abdominal examination: Liver (hepatitis, abscess) or loin tenderness (perinephric abscess).

Skeletal examination: Arthritis or osteomyelitis (focal tenderness).

Rectal examination: Focal tenderness suggests pelvic abscess.

STEP # 05: After history and examination, did you find any cause for prolonged fever?

With clinical suspicion of any disease, investigations should be directed to confirm or exclude the suspected disease.

Unexplained prolonged fever... What is the cause?
When history and physical examination fail to reveal an evident cause or to suggest a specific disease, the term “unexplained prolonged fever” or “fever of unknown origin
(FUO)” can be used. These terms should be restricted to cases of documented fever with duration of at least 10-14 days.

STEP # 06: Whether to admit or not?

In patients with good general condition and a rather short history, simple investigations (CBC, ESR, CRP, urine analysis) can be made on an outpatient basis.
Normal laboratory findings in this group indicate that the illness is mostly a benign viral infection. Reassurance and follow-up are important.

Patients with clinical findings indicating that the illness is significant should be hospitalized and further investigated. Hospitalization is also indicated in those with abnormal results of initial simple investigations.

Hospitalization is useful for several reasons:
a. Documentation of fever: Temperature should be regularly measured by a reliable person to exclude the possibility of “factitious or false fever”.
b. Drugs should be avoided as much as possible to exclude the possibility of drug fever. In this case, fever will subside within 1-3 days of discontinuation of the responsible drug.
c. Close observation for the general condition (appetite, activity, reaction to stimulation), presence of rigors (septicemia, malaria) or appearance of new symptoms or signs. Frequently, the fever may subside spontaneously without any specific therapy and even before completing the investigations.

STEP # 06: Investigations in children with unexplained prolonged fever

Nonspecific Investigations to confirm the presence of significant illness
Complete blood count (CBC): Leukocytosis, leukopenia or eosinophilia (larva migrans).
Erythrocyte sedimentation rate (ESR): Above 30 mm (first hour).
C-reactive protein (CRP): Above 20 - 30 mg/liter.
Chest X-ray: Pneumonic consolidation or pulmonary infiltrate.

Specific investigations to identify the causative disease
Initial investigations
Blood culture (aerobic and anaerobic): May be repeated.
Urine culture.
Tuberculin test and culture of gastric washing.
Blood film for malaria.
Common serological tests: Typhoid, infectious mononucleosis (monospot), brucella.

When the above specific initial investigations are negative
Specific blood culture for listeriosis, leptospirosis, tularemia.
Specific serological tests for leptospirosis, tularemia, toxoplasmosis.
Bone marrow examination (for leukemic blast cells) and culture (bacteria).
Abdominal ultrasonography: For liver abscess, epinephric abscess.
Echocardiography: In patients with preexisting cardiac disease (infective endocarditis).

When all of above are negative
Lymph node biopsy: May reveal lymphoma.
Radioactive scanning: May reveal osteomyelitis.
Total body CT scanning or MRI: May reveal hidden tumors.

Remember: International studies showed that in 25% of cases, the cause remains unknown even after exhaustive investigations.

STEP # 07: Blind empirical drug therapy may or may not be started? When indicated?

Blind empirical drug therapy should be generally avoided as it may mask the condition and makes the diagnosis more difficult. Exceptions to this rule are:
a. Blind antibiotic therapy in patients with the clinical diagnosis of septicemia but the organism could not be isolated.
b. Blind antituberculous therapy in sick patients with cachexia and weight loss and when the possibility of tuberculosis is strongly standing in spite of the negative laboratory investigations.



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