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June 14, 2008

What Is Naproxen Test ? Fever Of Unknown Origin

What Is Naproxen Test? Fever Of Unknown Origin


Fever of whatever etiology still remains a perplexing problem to both clinicians and investigators. Despite its established role as a Cardinal Sign of Infection, it remains elusive if not surprising in terms of final outcome. Increasingly, its role in Connective Tissue Diseases, Malignancies and Other Inflamatory isorders is slowly supplanting the exclusivitly of the symptom to just infectious conditions.

The likely identification of the cause of fever is crucially dependent upon meticulous history-taking and thorough physical examination coupled with useful ancillary and laboratory procedures. A dilemma arises when the diagnostic aids do not provide the expected results. Subjecting the patient to more laboratory examinations may provide an ordeal rather than a diagnosis. Shotgun Antimicrobial Therapy May Result in a Superinfection rather than a cure. The need to categorized prolonged fever in terms of specific etiology is essential in establishing a direction for the clinician's plan of action. Clinical studies have shown that The Most Common Causes of Prolonged Fever are Infections and Neoplasm. Based on this premise the Naproxen Test may provide a simple and economical tool in the causative differentiation of fever.

A seven-year study by Chang confirmed that naproxen test value in differentiating between infections and neoplasm. Lysis of fever upon administration of the drug favors a presumptive diagnostic of neoplastic fever. On the other hand, failure points to an infectious cause.

Naproxen Test


The patients were given Naproxen Sodium at 500 mg/tablet, one tablet every 12 hours p.c. for a total of 4 doses. Body temperature was taken orally every two hours prior.

Naproxen 500 mg/tablet Every 12 Hours P.C For 2 Days


Fever lysis after or within the time frame of drug administration was interpreted as suggestive of either a neoplastic condition or a connective tissue disease.
Nonresponse of the fever to the drug was taken to suggest an infectious condition.

Naproxen Administration was discontinued if any of the following were noted :

1). Hypersensitivity reaction,
2). Abdominal complaints, or
3). Patient refusal to take the drug.

Neoplastic Fever is the second most common cause of fever in cancer patients after infection. The establishment of the etiology of fever in patients with malignancy however, remains to be a challenging diagnostic scenario for clinicians. Distinguishing between infectious fever and neoplastic fever is of paramount importance in cancer patients because of the urgency and necessity for appropriate treatment in these immunocompromised hosts. Postulated pathogenic mechanisms for its occurrence include massive tumor necrosis, extensive neoplastic cell destruction, local inflammation due to ulceration of normal or malignant tissue, leucocytic infiltration of the neoplasm, interference with conjugation of pyrogenic steroids secondary to liver metastases and excessive heat production by tumor cells.

The more recent mechanism involves induction of pyrogenic cytokines such as tumor necrosis factor, interleukins 1 and 6 and interferon by the tumor cells itself or by host macrophages in response to the tumor. Cytokines stimulate production of prostaglandin E2 which act on the hypothalamus causing a change in the thermostatic set point. Naproxen is a non-steroidal anti-inflammatory drug which acts as an inhibitor of cyclooxygenase. It has been demonstrated to have both analgesic and antipyretic effects.

Dr. Chang pioneered the use of the 'Naproxen test' as a clinical tool in the differential diagnosis of fever of undetermined origin (FUO) in patients with cancer in a study conducted at the Oncology Unit of the Good Samaritan Hospital in Dayton, Ohio. The study population consisted of patients with FUO and suspected or diagnosed malignancy. Naproxen was administered at 250 mg twice a day orally at 12-hourly intervals for at least 3 days. The results of this study were promising. However validity was not established because of the lack of an independent, blind comparison with a reference standard. Instead, a correlation of the final diagnoses of FUO in all patients with their response to antibiotics and naproxen was done.

Subsequent observational studies on small groups of patients with specific malignancies similarly
had promising results, but likewise suffered from this critical flaw. This precluded further estimation of the sensitivity, specificity and likelihood ratios of the naproxen test. It is suggested that the more appropriate reference standard would be the absence of infection after extensive and thorough laboratory work-up coupled with the absence of any clinical deterioration without administration of any antibiotics on continued follow-up for at least a period of 2 weeks. Specifically, the more convincing evidence that a patient does not have any infection despite extensive work-up would be the non-deterioration of the patient in the absence of any antibiotics during a prolonged follow-up period.

With the advent of modern diagnostic technology, it is timely that the usefulness of this
test be re-evaluated in the present decade. In the Philippines, it is best that this test be validated in a tertiary center with a laboratory and radiology department that is equipped with highly sensitive diagnostic and imaging procedures that are needed to rule out any infection from bacterial, viral, fungal or parasitic etiology. Likewise the staff should be competent in the performance and interpretation of these procedures.

Larger studies with a spectrum that would be representative of both hematologic and solid tumors are needed to confirm or refute the naproxen test as a valid and accurate tool in discriminating between neoplastic and infectious fever. To date neoplastic fever remains a diagnosis of exclusion. If the potential predictive value of this inexpensive and easy to perform test could be established, prolonged empiric antibiotic therapy and extensive fever work-up could be minimized. Likewise, delay in institution of chemotherapy could be prevented. This could all translate into improved quality of care and quality of life for the patient in terms of less medical expenses, less discomfort and inconvenience for the patient.

  1. The Naproxen Test was unequivocally positive in malignancies & connective tissue diseases.
  2. Malignant Lymphoma was the most common malignancy.
  3. Enteric Fever & Malaria were the most common infectious diseases with a true negative response. However, enteric fever also gave the highest false negative response.
  4. Amoebic Liver Abscess, Extrapulmonary Tuberculosis, Viral Hepatitis, Pneumonia, Recurrent Urinary Tract Infection, & Pulmonary Tuberculosis
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1 comment:

dany chandra said...

I strongly agree with your opinion, informative and useful. More power. Naproxen Sodium

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