Wednesday 26 March 2008

Answers to Case: Patient with Fever, Headache and Sore Throat

Dear Bloggers

Here are the answers to the case from last week.

Question:

1) From just the history and physical examination, list the problems with this patient.

  • Fever- low grade
  • Headache- temporal and occipital location
  • Sore Throat
  • Tongue pain
  • Restricted Jaw opening - TRISMUS
  • Shoulder pain
  • Fatigue / lethargy
  • Lymphadenopathy
  • Weight loss of 2kg
  • Change in sense of taste and coated tongue
  • Hepatitis C infection
  • Raised AST & ALT + INR
  • Normocytic Anaemia
2) Was there any indication to do a lumbar puncture in this case? Were there any contraindications? What is your interpretation of the result?
  • Apart from the fever, there was no obvious indication to perform a lumbar puncture in this case. The patient despite having some headache said it was made worse when combing his hair. Meningeal pain does not worsen by touching the skull. There were also no meningeal signs from symptoms or physical examination. Moreover, there was an obvious relative contraindication that being the raised INR. In fact, an INR >1.4 is a relative contra-indication against LP until the coagulopathy has been corrected (see UpToDate 16.1-Lumbar puncture: Technique; indications; contraindications; and complications in adults).
  • There is a real risk of puncturing a blood vessel leading to uncontrolled haemorrhage with the potential of causing spinal cord compression leading to paresis, from an extradural haematoma. However, if the need for a lumbar puncture is high, an experienced practitioner should perform the lumbar puncture with the aim of obtaining CSF on the first pass of the needle to avoid unnecessary trauma. Some practitioners recommend fluoroscopic examination to avoid puncturing small blood vessels.
  • The LP results show that indeed there was trauma making the result somewhat difficult to intepret. However, in view that there are generally 1 white cells for every 1000 red cells, by scaling down the figures one would obtain a mildly raised neutrophil count. However, the LP was in fact repeated, which was again slightly traumatic and this revealed an otherwise normal white cell differential. Gram stain was again negative.

3) What other tests would you like to perform on the day of admission?
  • In view of the above history, the diagnosis of Giant Cell Arteritis with Polymylagia Rheumatica is highly likely. Therefore, an Urgent ESR should be obtained. The patient also requires an Urgent Opthalmological Consult to look for retinal vessel occlusion which might be asymptomatic.
  • Moreover, in view of the sore throat, throat swabs for streptococcus, adenovirus should be obtained. EBV and CMV levels would also be useful here in view of the lymphadenopathy, abnormal liver function and anaemia.
  • Three sets of blood cultures should be obtained and and a cardiac echo performed.
  • In view of the Hepatitis C infection, a mixed cryoglobulinaemia is a possibility although there are no skin ulcers, so obtaining cryoglobuilin levels would be useful for purposes of exclusion.
  • Autommune Profile including ANCA, Rheumatoid Factor, ANA, etc
  • TB PPD skin test could be performed and a chest Xray to look for typical TB shadows (there was no such problem in this case). Aiming to rule out TB should not delay the start of steroids in this severe vasculitic condition because of the risk of blindness and stroke. If TB is also considered likely and cannot be ruled out, then treatment for this should also be commenced empirically with the steroids until such tests rule in or rule out the infection, if indeed that is possible (See UpToDate 16.1- Major side effects of systemic glucocorticoids).
  • Although this patient has Hepatitis C infection, starting steroids should not be delayed.
4) What is your diagnosis? What one test will provide the definitive diagnosis here?
  • Suspected diagnosis was:
Giant Cell Arteritis with Polymylagia Rheumatica.
  • An urgent temporal artery biopsy should be obtained.

5) What treatment would you start and when? How long do you continue such therapy and what other considerations are necessary?

  • Oral prednisolone 40-60mg/day should be started immediately even before biopsy is taken because of the high risk of visual loss, stroke and dissection (please see UpToDate 16.1)
  • Steroids should be kept at high dose for 2-4 weeks monitoring symptoms and ESR. Then slow tapering over 1-1.5 years
  • Aspirin should also be given as it reduces the risk of stroke and other vascular events when compared to steroids alone.
  • In view of high dose steroids plus aspirin, a proton pump inhibitor (PPI) should also be given to reduce the risk of gastric haemorrhage.
  • Steroids can cause osteoporosis and consideration should be given to commencing a bisphosphonate on a weekly basis e.g. Alendronate 70mg. These drugs can also cause gastric irritation and so once a week dosing should be considered. This is yet another reason to provide PPI treatment.
  • The patient should be monitored for diabetes and on discharge should be kept under regular outpatient follow-up and the patient should monitor their glucose by use of urinary test strips.
  • Opportunistic infection should be considered in patients who are imunosuppressed by corticosteroids especially with doses >10mg /day or a cumulative dose > 700mg. Patients have a higher risk of pneumonia and infection with pneumocystis jiroveci. However, the risk is still small and hence, there is no current recommendation for use of Pneumocystis prophylaxis in patients on steroids alone (see UpToDate 16.1-Major side effects of systemic glucocorticoids )


Here is an excellent comment on the case from Dr Masami Matumura of Kanazawa University Medical School.

This case is difficult to diagnose, but challenging case.

Questions
1) From just the history and physical examination, list the problems with this patient.

I listed problems as follows;

1 Fever
2 Headache (which was worse when he combed his hair, suspect scalp pain)
3 Sore throat
4 Fatigue
5 Weight loss
6 Shoulder discomfort
7 Inability to open mouth
8 Impaired taste
9 Tongue pain
10 History of Hep C infection
11 Redness of throat
12 Lymphadenopathy
13 Anemia
14 Tachycardia
15 Tender temporal and occipital areas on the cranium
16 Tender in the neck

2) Was there any indication to do a lumbar puncture in this case? Were there any contraindications? What is your interpretation of the result?

I think there was no indication of lumbar puncture in this case. Because physical examination didn't disclose meningisumus. No neck stiffness, Kernig's and Brudzinski's signs were negative.
I think there were no contraindications for lumbar puncture. PT-INR was 1.52, slightly high. If meningitis is highly suspected, lumbar puncture should be performed.
Considering of the result of cerebrospinal fluid (CSF), traumatic tap is highly suspected. Because count of RCC in CFS was 1600. In this situation, I would order Indian ink stain. We can rule out cryptococcal meningitis.

3) What other tests would you like to perform on the day of admission?

I will order ESR and ALP in this case first. ESR must be high, approximately 100 mm/hour.

4) What is your diagnosis? What one test will provide the definitive diagnosis here?

My diagnosis is polymyalgia rheumatica (PMR) associated with giant cell arteritis (GCA)

Again my problem list is as follows;
1 Fever
2 Headache (which was worse when he combed his hair,
suspect scalp pain)
3 Sore throat
4 Fatigue
5 Weight loss
6 Shoulder discomfort
7 Inability to open mouth
8 Impaired taste
9 Tongue pain
10 History of Hep C infection
11 Redness of throat
12 Lymphadenopathy
13 Anemia
14 Tachycardia
15 Tender temporal and occipital areas on the cranium
16 Tender in the neck

Chronic inflammatory process is highly suspected by problem No. 1, 4, 5, 13, and 14. Collagen disease, infection, and malignancy should be differentiated. I would think problem No. 2, 3, 6, 7, 8, 9, 11, 12, 15, and16 are consistent with manifestations of PMR/GCA.
Another differential diagnosis is Sjogren’s syndrome associated with vasculitis. Problem No. 3, 8, 9, 11, and12 are manifestations of Sjogren’s syndrome. I have never seen a patient with Sjogren’s syndrome associated with vasculitis. But it is my one of differential diagnosis.
Another differential diagnosis is cryptococcal meningitis. This is less likely. I mentioned above.

I listed differential diagnoses as follows:
  • PMR/GCA
  • Sjogren’s syndrome associated with vasculitis
  • Microscopic polyangiitis
  • TB
  • Cryptococcal meningitis
  • Infective endocarditis
  • Lymphoma

In this case, PMR/GCA is most likely. This patient is 70 years old man and discloses fever, headache (scalp pain), sore throat, fatigue, weight loss, shoulder discomfort, inability to open mouth (suspect claudication), tongue pain, anemia, tachycardia, tender in the neck, and tender
temporal and occipital areas on the cranium. Patient history and physical examination tell us the chronic inflammatory condition and characteristics of PMR/GCA. ESR is usually greatly increased in PMR/GCA. ALP is also increased in PMR/GCA.

Biopsy of the temporal artery is needed.

Criteria for the diagnosis of PMR/GCA is as follows;
(Bird, 1979)
1 Age > 65
2 Onset <>
3 Morning stiffness > 1 hour
4 Depression or weight loss, or both
5 Bilateral shoulder pain and stiffness
6 Upper arm tenderness
7 ESR > 40 mm/hour

If any three features, Sensitivity 92% Specificity 80%

5) What treatment would you start and when? How long do you continue such therapy and what other considerations are necessary?

I would want to confirm the existence of vasculitis and rule out TB. The possibility of TB is low, because the patient doesn’t have respiratory symptoms and abnormal findings in chest X-p.
Involvement of vessel may be segmental in patients with GCA, the diagnosis may be missed on routine biopsy. Serial sectioning of biopsy specimen is recommended. After the biopsy, glucocorticoid therapy should be started. Treatment should begin with prednisolone, 40 to
60 mg per day for four weeks, followed by tapering to a maintenance dose of 7.5 to 10 mg per day. This treatment should be continued for at least 1 to 2 years because of the possibility of relapse. If my diagnosis is correct, we can expect dramatic clinical response to prednisolone
therapy in this case.

The patient is 70 years old man. We should be careful of side effects of prednisolone therapy, especially opportunistic infection including pneumocystis pneumonia or cytomelgalovirus infection. Osteoporosis is another important side effect of prednisolone therapy in high aged patients. I would prescribe bisphosphonate to him when I start prednisolone therapy.

He has Hep C infection too. The existence of Hep C infection is not contraindicated for prednisolone therapy, however, we should monitor his liver function closely in steroid tapering phase.

Thank you very much for showing me interesting case presentation.

Thank you for such an excellent case commentary Dr Matsumura.

The result of this case indeed revealed the diagnosis of Giant Cell Arteritis with Polymyalgia Rheumatica. This was confirmed by a positive biopsy result.

Echocardiogram revealed no vegetation and blood cultures were negative.
Autoimmune screen was unhelpful with all major antibodies being negative e.g. ANA, ANCA

There was an unfortunate delay in starting the steroid therapy and the patient experienced some partial visual loss and unilateral numbness of his fingers and toes.
Opthalmological examination revealed occlusion of some of the retinal vessels.

Steroids were commenced immediately following this deterioration at a dose of 40mg prednisolone / day, and the patient's symptoms resolved before the result of the biopsy was known.

Moral of This Story

History and Physical Examination can give you the diagnosis to a case despite the difficulty of putting together the symptoms and signs. If GCA is suspected, steroids must be started immediately and not delayed because of the real problem of visual loss, as occurred in this case.

Delay potentially occurring to confirm the diagnosis by biopsy or the concerns about other diseases such as TB should not deter you from starting empirical steroid treatment for GCA. If there are concerns about other diseases such as TB, then empirical treatment should also be commenced for these until they are ruled in or ruled out.
GCA is one of those diagnoses where there are no 100% accurate tests and even the temporal artery biopsy can be negative.

Hence, you have to rely on what the patient says to you and what you find by examination and trust in yourself to have the confidence to start a treatment that can have many adverse side-effects by can also be not only sight saving but also life saving.

Please consider....

A Patient with Fever, Headache and Sore Throat

Dear Bloggers

Today, I bring you another most exciting case.

It is up to you to try and work out the diagnosis here.

A 70 year old male was see in another hospital's outpatient clinic with the following symptoms:

  1. Fever
  2. Headache
  3. Sore Throat
Fever: The above symptoms had started gradually three weeks before. The fever was observed by the patient to be about 37.5 degrees and with slight increase above this in the evenings. There were no rigors associated with the fevers.

Headache: The headache had also come on gradually and was located in the sides of the patient's head and also at the base of the skull at the back. The headache was worse when the patient combed his hair. There was no associated nausea, vomiting, neck stiffness or photophobia. The patient denied visual disturbance and there was no limb weakness described. There was no history of a 'thunder clap' severe headache and no visual aura's.

Sore throat: The sore throat also started at the same time. The patient had been to see a local doctor and inspection of the throat revealed redness but no exudate. No throat swab examination was taken. An upper respiratory infection was favoured, and a 3rd generation cephalosporin was prescribed on that basis but no resolution of symptoms was observed.
The patient's symptoms were becoming progressively worse and he was feeling increasingly tired and had observed a loss of 2kg in body weight.

On further questioning, the patient was also experiencing shoulder discomfort and had in fact been feeling tired for almost 6 months. Moreover, the patient also complained of a recent inability to fully open his mouth. Also, his taste had become impaired. There was also confirmation that there was some tongue pain whilst eating food.

Body Systems Review

The patient denied joint and muscle pain and she described no swelling, no skin rashes, no cough / sputum / dyspnoea / haemoptysis / night sweats. There were no cardiac symptoms such as chest pain or palpitations. There were no other gastrointestinal symptoms such as epigastric pain / vomiting / constipation / diarrhoea / jaundice / change in colour of stool + urine / haematemesis / haematochezia. The patient had no obvious neurological symptoms.

The patient was a non-smoker and there was no history of contact with tuberculosis.

Previous medical history included Hep C infection following vaccination as a child.
There were no other medical problems.

The patient was taking no medications and there were no known drug allergies.

The patient was retired and lived with his wife in a 3rd floor apartment. There was a working elevator which had never had problems. However, when asked, he considered that it might take him several minutes to walk up the several flights of stairs if the elevator was to break because of fatigue.

On examination

The patient looked chronically ill but was fully alert and conversant.

HEENT: His tongue was coated with a thick white covering which was confluent rather than patchy. The oral mucosa was not coated. The throat was mildly red with no exudate. The thyroid was normal size and non-tender. There were several lymph nodes below the mandible bilaterally which were mildly tender, smooth and mobile. They were <1cm>
There was conjunctival pallor but no scleral jaundice.

Hands revealed no peripheral signs of systemic disease.

CVS: pulses were all present. There was a tachycardia of 100/min regular. JVP was not raised.
Heart sounds were normal with no murmur and no added sounds. There was no leg oedema and no evidence of deep vein thrombosis.

RESP: RR- 18/min, Sats 98% on room air, trachea central, no tracheal tug, normal percussion note and normal breath sounds.

ABDO: Soft, non-tender, no masses, no organomegaly, normal bowel sounds. Rectal examination was normal and revealed no faecal occult blood.
There was no jaundice and no signs of chronic liver disease.

CNS: Cranial Nerves 2-12 were normal. Taste sensation was not checked. Fundoscopy was not performed.

PNS: No neck stiffness, Kernig's and Brudzinski's signs were negative. Jolt accentuatuation was negative. Tone, power, reflexes, coordination and sensation were within normal limits.

Musculoskeletal Examination revealed tender temporal and occipital areas on the cranium. There was full range of movement of the neck but generally tender. There was no joint pain or swelling and muscles were non-tender.

Skin Examination: There was no obvious skin abnormality.

Bloods: revealed a normocytic anaemia with a haemoglobin of 8g/dl. Platelets were slightly raised. White cell count was slightly elevated at 12.1 x10^9/L. Liver function tests were three times normal for AST and ALT. HCV PCR was positive. INR was 1.52. Renal function was normal.

Urine: normal.

Lumbar Puncture was performed revealing RCC 1600, WBC 23 (neutrophils 15, Lymphocytes 8), normal protein and glucose. Gram stain negative.

CXR: Normal

ECG: sinus tachycardia.

Questions

1) From just the history and physical examination, list the problems with this patient.

2) Was there any indication to do a lumbar puncture in this case? Were there any contraindications? What is your interpretation of the result?

3) What other tests would you like to perform on the day of admission?

4) What is your diagnosis? What one test will provide the definitive diagnosis here?

5) What treatment would you start and when? How long do you continue such therapy and what other considerations are necessary?

The answers to this fascinating case will be provide in the near future. Please send me your answers so that they can be placed on the answer page.

Happy sleuthing.... :-)