11 year old boy was admitted in another major hospital with fever for one and half months . Previously healthy with no significant illness. His father was diagnosed as sputum positive pulmonary tuberculosis and was on CAT 1 ATT from RNTCP .All the investigations done for prolonged fever did not give a clue to diagnosis. He developed cervical lymph node enlargement on left side which was multiple size ranged from 1 to 1.5 cm tender,not matted.They did lymph node biopsy, result was non specific hyperlasia. Mantoux was positive, chest X-Ray negative. As the fever persisted,he was put on CAT I ATT
As the fever and cervical lymph node persisted after three weeks of ATT he was referred to us.
At the time of admission his vitals were stable.Weight and height was within normal range and he had mild pallor. Cervical lymph nodes palpable on left side. No other lymph nodes. No cutaneous bleeding manifesations or rashes. Joints were normal.
His system examinations were within normal limits. No hepatosplenomegaly
Teaching points for Under graduates
Prolonged fever is one of the most difficult challenges. How to approach ?
In pediatric age group Major group of problems for fever are,
1. Infections.
2. Malignancies
3. Connective tissue diseases
These three constitute 99 percent.
These three constitute 99 percent.
Rarer possibilities of fever are problems of heat generation or dissipation .
a. Hyper - catabolic states where temperature generation increased eg thyrotoxicosis
b. Temperatue dissipation. eg problem with sweat glands, disorders of autonomic nervous system, water deprived states where sweat formation is defective like ADH deficiency, drugs and poisons ,
c.hypothalamic disturbances which set the thermostat at higher level
All these are very rare but interesting scenarios which causes confusion .
How will you proceed in these difficult situation ?
Ensure vitals are stable .
Do a proper clinical examination , unbiased with the opinions and investigation results so far.
If no clues, stop all drugs and arrange for proper temperature recording and temperature chart for next few days ( Good temperature chart is the most useful investigation. It should record the temperature and other related parameters also like pulse rate , respiration, remarks of adding a drug, withdrawing a drug ,any events (eg rash) etc also should be marked in temperature chart ).
Duration of fever is one very useful point. Most of the common viral infections are self remitting and last for days only.Viral fever with a bit prolonged course constitute small share of viral infection eg IMN , cytomegalovirus, hepatitis B&C( prolonged fever is not common in HIV per se ).
Most of the bacterial infections will develop clinical clues within one week and course is usually weeks either responds to treatment or result in complications. Exceptions of chronic bacterial infections where clinical clues may be lacking are enteric fever and urinary tract infections, tuberculosis, rarely brucella. Out of these urinary tract infections and tuberculosis may remain for weeks without diagnostic clues .
In fever lasting for months,chronic infections like TB, malaria urinary tract infections should be suspected. In most of these cases also some clinical clues occur by time.
Malaria is one of the common chronic infections where clinical clues may be missed
Ricketsiels and other unusual organisms are to be considered depending on the locality
Next is the list of possibilities is malignancy. All of us know that common malignancies in pediatric age group presenting with fever are hematological ones. If the presentation is typical, it wont be difficult. But sometimes, hematological malignancies , neuroblastoma may present without typical features and prolonged fever only .
Connective tissue disorders again may present with fever only . Most common manifestations are joint , muscle and skin involvement. Occasionally it may present without any of the above classical features. Especially, systemic onset of JIA
If documented fever last more than months and no clinical clues , think about the rarer situations mentioned above .
In this case as he was on ATT for three weeks and had an open contact with PT Mantoux positive we continued the treatment and observed him for one week with proper temperature charting
Follow up
He developed arthritis of small joints of hand and both knees. These evolved simultaneously over 48 hours. No hip or spine involvement. No associated rash. Other findings remained same . No ocular involvement.
Blood uric acid was high.
ANA ( Elisa ) was positive from medical college, repeat test was done which came as negative.
Rheumatoid factor negative.
Bone marrow biopsy done, showed erythroid hyperplasia - other series normal .
Lymph node biopsy report, reactive hyperplasia and no granuloma.
Urine examination routine and culture was normal.
We thought of the the possibility of Pyrazinamide induced arthritis and it was stopped .
Fever persisted as such. He was not sick. Arthritis was remaining in the same distribution and severity. He was able to move around .
Among the blood investigations Ds DNA came positive 90 ( normal less than 60)..
ATT was stopped after one month and he was put on Naproxen and methotrexate 15 mg /m2.
With this his fever subsided and joint pain and swelling relieved . He was discharged .
He was readmitted after two weeks as the liver function deranged .
All drugs were stopped.
Possibility of SLE was considered and ANA profile was sent which showed Ds DNA negative and only RNP positive .
Throughout ESR remained above 100
C3 was 49 C4 was 6
24 hour urine protein was 400 mg
DCT was negative
As the results were not conclusive and he had arthritis he was put on 200 mg hydroxy chloroquine only .
He continued to have fever and he had another type of rash, plaque of five centimeters not itchy which persisted on his shoulders and axilla
Possibility of SLE was higher.
His repeat ANA and Ds DNA came strong positive
He was put on prednisolone 1.5 mg per kg. Hydroxy chloroquine was continued
His symptoms all better. Fever subsided, rash disappeared . Arthritis subsided.
Chart of investigations done so far
He was admitted after two weeks with generaised odema .
No jaundice.
No dyspnea. JVP was not raised. Cardiovascular system examination within normal limits
Ascitis clinically and USG wise .
Investigation at this stage
Urine 24 hour protein was 250
Serum albumin 3.5 gram
Serum cholesterol 231mg /100ml
Oedema was bit difficult to explain
He was put on mycophenolate mofetil 500 mg daily orally.
No response after two weeks. Odema , ascitis worsened.
One dose of Cyclophosphamide IV 500 mg /m2 was given .
Oedema, ascitis relieved.
Now,
He is on follow up, asymptomatic and continuing mycophenolate mofetil.
Two more doses of Pulse cyclophosphamide given
Message
Prolonged fever , contact with Open pulmonary TB in father, significant cervical lymph node and Mantoux positivity .. everything points towards tuberculosis ..
Even in classical scenarios we may go wrong, and in connective tissue disorders time will reveal the reality .
Here again many of the decisions may be questioned, decisions were not ideal.
Experts may have a different view .
