Fever of unknown origin is a frustrating diagnosis for both the patient and the physician. It is rather a failure on the part of the physician being not been able to make a diagnosis.

When the physician is not able to make a diagnosis, the frustrated physician then tries to prescribe very broad-spectrum antibiotics. These antibiotics are usually very costly and require an intravenous or intramuscular administration.

A brief case-scenario is presented here. This will be followed after two days by a discussion and further follow-up of the patient.

Readers are requested to give their input.


medical interview

History of the patient with Fever of unknown origin:

A 20 years of age female was brought to my clinic with a four weeks history of:

  • a high-grade intermittent fever, documented as 104 F on certain occasions.
  • generalized body aches and pains, and
  • a weight loss of four kgs (attributed by the attendants to anorexia and reduced appetite)

The patient did not have any significant complaints pertaining to a specific system. She denied having a cough, chest pain, bladder & bowel symptoms, joint swelling, early morning stiffness, bleeding from any site, and neurologic symptoms.


clinical examination

On examination, she was febrile with a temperature of 102 F. She was in distress due to body aches.

General physical examination revealed a coated tongue and mild dehydration. She was not pale or jaundiced, had no significant lymphadenopathy, and did not have skeletal or muscle tenderness.

Examination of the chest, abdomen and central nervous system were also unremarkable.


Investigations which were previously done for Fever of unknown origin:

During this period, she visited multiple doctors and was investigated. Her laboratory  investigations are given below:

Blood CBC

Hemoglobin 10 gm/dl
WBCs 26000/ul
Platelets 430,000/ul
Neutrophils 80%
Lymphocytes 15%
Peripheral smear No Abnormal cells seen

 

Blood Chemistry

Bilirubin 1 mg/dl
ALT 45 IU/l
Alkaline Phosphatase 130 IU/L
BUN 12 mg/dl
Creatinine 0.6 mg/dl

 

Other investigations

Urinalysis Normal
Chest X-ray Normal
Ultrasound Abdomen Normal study
Echocardiography (repeated twice) Normal (No vegetations seen)
Blood Cultures No growth
Urine Cultures No growth
Thick & Thin smear No malarial species seen
ICT-MP Negative
Typhidot IgM & IgG Negative

She received three courses of antibiotics that included levofloxacin, Azithromycin, and injectable Ceftriaxone (Rocephin).

She received her 10th injection of Rocephin (Ceftriaxone) one day before visiting my clinic.


What investigation may be advised at this stage to reach a diagnosis?


Let’s proceed further …

Although few people have commented here, they are probably the best responses.

Most of you have the following disorders in mind:

  • Autoimmune rheumatic disease (Collagen Vascular disease)
  • Adult-onset Still’s disease
  • Pyrexia due to a hidden abscess (for example, a liver abscess, perinephric abscess, and a psoas abscess, etc)
  • Tuberculosis

Because the patient has had multiple antibiotics, some response should have been seen if an infective etiology was to be suspected.

Furthermore, she had multiple investigations done prior to this visit, the attendants were not willing for any further workup.

So, I just advised two investigations and kept the others in the plan.

Investigations advised:

  • ESR: 120 mm in the first hour
  • Serum Ferritin: 28000 ng/ml

Extremely high levels in this range with the suggestive clinical features were indicative of the diagnosis of Adult-onset stills disease.


Treatment of the patient …

The patient was started on an NSAID, prednisolone, and other supportive treatment. All antibiotics were stopped.

She was asked to monitor her temperature, weight, and development of any new symptoms and signs.

CECT of the neck, chest, abdomen, and pelvis were kept in the plan had the patient had a persistent febrile state.

The patient responded very well to the treatment and during the past two weeks, she had only one episode of low-grade fever. Her appetite normalized and she started gaining weight.

A tapering dose of steroids has been recommended. If the daily required dose exceeds 7.5 to 10 mg per day, a steroid-sparing agent like methotrexate or other DMARDs will be added later.


 

Which other condition, apart from Adult-onset stills disease, is associated with extremely high levels of ferritin?

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FarhanARIF MUMTAZM waqasAsim alviShahzad Recent comment authors
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Tehseen
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Tehseen

Sir any history of arthralgias or rash ?
Next ESR, CRP, serum ferritin should be done.
We should also keep Ct neck, chest, abdomen , pelvis & Bone marrow biopsy ( with culture) in plan.

Tehseen
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Tehseen

Also Serum ANA

Shahzad
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Shahzad

How about autoimmune screen, esr , vasculitic screen, may be investigation for tuberculosis, repeat blood cultures , malarial screen. Low threshold for CT TAP and bone marrow biopsy.

Asim alvi
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Asim alvi

ESR CRP Procalcitonin PPD ferritin ANA thyroid profile .

PLAN CT chest abdomen pelvis
BMBx with culture .

Tehseen
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Tehseen

Hemochromatosis

ARIF MUMTAZ
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ARIF MUMTAZ

VERY RAISED FERRITIN……… HLH,HEMOCHROMATOSIS