A does not always equal B

Dear Colleagues

I was recently presented an elderly man with a longstanding history of rheumatoid arthritis, who presented with an acute onset of fever followed by a cough with sputum. 

History

The patient experienced a fever of 38ºC with associated sweats. There were no chills or rigors. 

The cough was productive of some sputum, albeit limited in quantity and frequency. There was no chest pain or dyspnea. 

The patient complained of posterior neck pain, but this was not a new symptom having been present for over 1 year. 

The patient lived with two other family members, but they were well. There were no new medications commenced in recent months. 

The patient’s rheumatoid arthritis was poorly controlled over the last 30 years leading to severe deformity of his hands and significant disability. However, he said that his symptoms were not worse recently.

He underwent total knee arthroplasties a decade ago for osteoarthritis of his knees. 

The patient was using methotrexate 4 mg once per week, folic acid 5 mg once per week, bucillamine, and tacrolimus 0.5 mg daily, respectively. 

The patient was a non-smoker, but he had been exposed to passive smoking over several decades years, working alongside his family members. He did not consume ethanol. 

The patient was initially seen at another hospital. There was no description of any physical examination having been undertaken there. However, notably his chest computed tomography scan showed infiltration in a crazy paving pattern, and his laboratory data showed an elevation of beta-D-glucan.

As a result, he was diagnosed with pneumocystis pneumonia secondary to immunosuppression. No confirmatory tests were performed. Sulfamethoxazole-trimethoprim was started as blind treatment.

Physical examination

On physical examination his vital signs were stable except for moderate hypertension. 

The patient was frail and emaciated, but not in acute distress.

HEENT: Normocephalic and atraumatic. Eyes - slight conjunctival pallor. No jaundice. Ear - normal. Nose - normal. Throat - missing many teeth; no active dental caries. Mild oral candidiasis (prior examination showed more extensive colonisation).

Cardiovascular examination: JVP: not elevated. Apex: No heaves/thrills. Heart sounds I & II: Distant. No 3rd / 4th heart sounds. No gallop rhythm, or rub. II/VI Levine ejection systolic murmur at the left parasternal border. No radiation to the carotid areas. Peripheral pulses all present and normal. No clinical signs of deep vein thrombosis.

Respiratory examination: Barrel shaped chest. Trachea central and shortened. Use of accessory respiratory muscles. Percussion: Hyper-resonant. Auscultation: Fine crackles in the mid left posterior chest with bronchial breathing and egophony. Otherwise, reduced breath sounds throughout. No high or low pithed wheezes.

Abdominal examination: No scars or hernial orifices. Soft, non-tender, non-distended. The liver could be palpated 1 cm below the costal margin and was non-tender. The spleen was impalpable. Percussion confirmed the above findings. The scratch test identified the liver to be spanning the epigastric area. Bowel sounds were normal. There was no costovertebral angle tenderness.

Rheumatological examination: 

HANDS - severe changes; ulnar deviation with subluxation at the MCPs. Mixture of boutonierre and swan neck changes in the digits. Z-deformity of the thumbs. There was no synovial swelling or increased temperature of the affected joints. 

ELBOWS: Preserved range of motion and no synovial swelling.

SHOULDERS: Muscle wasting around the joints. Destruction of the glenohumoral joints. No swelling or increased temperature. Able to lift his arms up to his head in the anteroposterior plane.

HIPS - Normal ROM.

KNEES - Evidence of bilateral knee replacements; increased temperature at the right lower knee joint area. No pain or tenderness.

ANKLES - Reduced ROM; no-tender and no increased temperature.

FEET - Claw toes.

DATA

Laboratory data did not reveal specific findings, except for a mild anemia, mildly elevated liver enzymes and renal dysfunction. 

Beta-D-glucan and D-Dimer were elevated.

The chest radiograph showed only hyperinflation, but no infiltrations.

The electrocardiogram showed non-specific findings such as p-mitrale and incomplete right bundle branch block. 

Chest computed tomography revealed a crazy paving pattern of interstitial changes.

IMPRESSION

It was considered that the patient had pneumocystis pneumonia based on the risk factors of immunosuppression, elevated beta-D-glucan and a consistent computed tomography pattern.

The patient was commenced on sulfamethoxazole and trimethoprim.

No induced sputa were examined and no bronchoscopy was performed.

ANOTHER LOOK!

Although the diagnosis may be correct here, it is by no means a certainty. Let’s reconsider the history. A typical diagnosis of pneumocystis pneumonia consists of many weeks of low grade fever, a non-productive cough and dyspnea, all of which are progressive. This patient had an acute presentation, making it more likely to be another diagnosis such as a viral or bacterial infection.

The beta-D-glucan elevation could have been due to the oral candidiasis in this case. Even mucosal colonisation can lead to elevated levels. The elevated levels indicate that there is a problem with a fungus, but it does not always equal pneumocystis pneumonia. 

To establish the diagnosis of pneumocystis pneumonia, it is usually recommended to obtain induced sputum or to perform a bronchoscopy with bronchoalvealoar lavage. The samples need to be stained for Pneumocystis jiroveci and/or a PCR test should be performed for the diagnosis.  

However, when it is difficult to obtain samples e.g. unstable C-spine, such as in chronic rheumatoid arthritis, the diagnosis can be inferred from the clinical picture. NOTE: there is an increased risk of an odontoid fracture in the cervical spine with neck manipulation in patients with long-standing rheumatoid arthritis.

In this case there are several other differential diagnoses which are related to the computed tomography crazy paving pattern which include:

- pulmonary embolism 

- tuberculosis 

- bacterial pneumonia (common), including mycoplasma

- acute interstitial pneumonia

- Goodpasture disease 

- drug-induced (bucillamine and methotrexate can cause interstitial pneumonia)

- lymphoma (note: tacrolimus is associated with lymphoma)

- sarcoidosis

The most compatible diagnoses associated with a rapid onset of symptoms are bacterial pneumonia or pulmonary embolism. 

The above list is not exhaustive, but it demonstrates that one needs to consider several diagnoses instead of jumping at one diagnosis. Confirmatory testing is the key. This means that A does not always equal B in terms of a computed tomography pattern equally one diagnosis.

In this case the bucillamine was stopped by chance because of the abnormal renal function. This drug could have been the cause or contributed towards the symptoms. Bucillamine is a very old rheumatology drug and this is no longer prescribed in modern day practice. 

The methotrexate was also prescribed at low dose (4 mg per week), which suggests that the management was not by a rheumatologist, but more likely via an orthopedic service. Note: In Japan, many rheumatology patients are managed by orthopedics because of the lack of trained rheumatologists. 

Moreover, UpToDate suggests that 1 mg folic acid is given DAILY, not weekly. Even giving folic acid on the same day as the methotrexate does NOT affect the drug’s efficacy. So this case reflects old practice and not current recommendations. 

TAKE HOME MESSAGES

• Never be satisfied with a brief history and physical examination. When dealing with a complicated history, especially past medical history and medications, one needs to take time to establish all the facts. 
• Medication can cause side effects!!! Could these be contributing to the patient presentation?
• Examine the patient carefully and completely. Do not take a few mins for such a complex patient. Take as much time as is necessary to understand them.
• When it comes to imaging studies, make sure you know the differential diagnosis of particular features. Even better still, obtain a formal radiological report rather than attempting to be a pseudo-radiologist. Please be aware that in many countries, doctors are do not report their own imaging. They always obtain the formal report of a radiologist; that includes chest radiographs as well!