A 47-year-old male with no medical history was referred to the St. Catharins Hospital (Eindhoven, the Netherlands) in May 2010 following a two-week history of fever and dyspnoea. There were no complaints of cough and no history of smoking. His mother died in an other hospital three months before this episode due to an unknown pulmonary infection.
On physical examination, the patient was dyspnoeic with 24 breaths per minute and an oxygen saturation of 88% on ambient air. His blood pressure was 115/70 mmHg with a heart rate of 105 beats/min. Body temperature was 38.8 degrees Celsius. Apart from bilateral inspiratory fine crackles no other physical abnormalities were observed.
Laboratory investigations showed a mild normocytic anaemia (haemoglobin 7.9 mmol/L), white blood count 3.7/nL and C-reactive protein 200 mg/L. Alanine-aminotransferase, aspartate-aminotransferase, alkalic phosphatase and gamma-glutamyl-transferase were all raised tenfold the upper limit. Serum electrolyte levels and renal function indices were normal.
Arterial gas analysis indicated pH 7.42, pO2 32 mmHg, pCO2 74 mmHg and bicarbonate 20.4 mmol/L.
Chest X-ray on admission disclosed bilateral consolidations (Fig. 1). Under suspicion of an atypical pulmonary infection broncho-alveolar lavage (BAL) was performed in the middle lobe. Direct smear microscopy examination of the sample and sputum for the presence of acid-resistant bacilli by using Ziehl-Neelsen method was negative. However the Polymerase Chain Reaction (PCR) for M. tuberculosis complex (MTBC) DNA was positive. Patient was tested HIV negative and no signs of immunosuppressive disorders were found.
During the first day of hospitalisation the patient became respiratory insufficient and tracheal intubation was necessary for five days. Treatment was started with broad spectrum antibiotics and on suspicion of a human tuberculosis infection standard anti-tuberculosis drug regimen was started. (isoniazid (H) 300 mg daily, rifampin (R) 600 mg daily, pyrazinamide (Z) 2000 mg daily, ethambutol (E) 1600 mg daily and pyridoxin 600 mg daily). Three weeks after admission the culture of the BAL fluid was positive for M. tuberculosis. Antibiogram showed a normal sensitivity pattern so the ethambutol was discontinued. In total the patient was treated with HRZ for two months followed by four months of HR.
14 days after initiating therapy sputum conversion was reached as presence of acid-resistant bacilli by using Ziehl-Neelsen method was negative in sputum sample, during 3 consecutive days. 10 Days after discharge from the intensive care unit patient was discharged from the ward. Clinical parameters all improved rapidly during his treatment. Furthermore the liver enzymes normalised during his hospital stay and remained normal during the total treatment period.
One month after initiating treatment for tuberculosis patient complained of lumbar back pain. Further radiologic evaluation using MRI showed abnormal signal intensity of L4, which was interpreted as spondylitis for which patient was referred to the orthopaedic surgeon. No further actions were taken and complaints resolved. At radiologic follow-up 3 months after MRI sclerosis was seen, but no signs of spondylitis anymore.
After treatment of the M. tuberculosis infection no abnormalities were seen on radiologic evaluation using X-ray of the chest, especially no parenchymal abnormalities or lymphadenopathy.
In November 2011 the patient was referred to the ophthalmologist by the general practitioner with complaints of red eye which did not resolve with chloramphenicol. The ophthalmologist diagnosed uveitis and initiated treatment with ocular prednisolon and atropine. Under this treatment uveitis resolved completely except for remaining synechia. Under suspicion of reactivation of tuberculosis the patient was referred to our outpatient clinic. At that time he had no pulmonary complaints, in particular no cough, weight loss or dyspnoea. He did not appear to be ill with a blood pressure of 115/70 mmHg, heart rate 105 beats/min and oxygen saturation 98% on ambient air. No physical abnormalities were observed. His body temperature was 37.1 degrees Celsius.
Laboratory investigations showed normal electrolytes including calcium and renal function. Erythrocyte sedimentation rate was 5 mm/h and C-reactive protein was <6.0 mmol/L. Angiotensin converting enzyme was 86 U/L (normal range 12-82 U/L).
Chest radiogram disclosed suspicion of mediastinal and hilar lymphadenopathy and interstitial densities in the right lobe which was confirmed on computed tomography of the thorax (Fig. 2).
Bronchoscopy was performed with lavage in the right upper lobe in combination with trans-bronchial needle aspiration (TBNA) of a pretracheal lymph node. No acid-resistant bacilli were found in the fluid lavage or in the cytologic material of TBNA. PCR for M. tuberculosis DNA was negative. Nevertheless since there was high suspicion on reactivation of pulmonary tuberculosis anti-tuberculosis drug therapy was initiated.
Two months following initiating treatment for M. tuberculosis another computed tomogram of the thorax was performed which was completely unchanged in comparison to the earlier scan, except now there were multiple nodules located at the right major fissure.
An endoscopic ultrasound with fine needle aspiration of a subcarinal lymph node was performed. Microscopic analysis revealed a population of lymphoid cells with spread granulomas. Necrosis was not observed. PCR for MTBC DNA was negative and acid-resistant bacilli were not present. Apart from the fine needle aspiration, a biopsy of an erythematosquamous lesion on the left upper arm was taken which revealed granulomatous structures, consisting of epitheloid histiocytes and few polynucleid giant cells, surrounded by small atypic lymphocytes. No central necrosis or caseiting was seen.
The patient was diagnosed with sarcoidosis and anti-tuberculosis therapy was discontinued.
Cardiac magnetic resonance imaging revealed no cardiac granulomas.
Diffusion capacity for carbon monoxide was normal and during exercise testing no oxygen uptake problem could be observed.
As there was no indication for initiating immunosuppressive therapy patient was seen at our outpatient clinic every three months for follow-up.