Respiratory symptoms in a patient on anti-tumour necrosis factor therapy; beware the negative enzyme linked immuno-spot (ELISpot) in suspected mycobacterial disease.

Mycobaterium tuberculosis (MTB) accounts for significant morbidity and mortality worldwide. Non-tuberculous mycobacteria (NTM) species, usually considered benign contaminants, are increasingly recognized to be associated with pulmonary disease in immuno-compromised hosts. The tuberculin skin test (TST) is of limited benefit in immuno-supressed individuals who often fail to mount a delayed type hypersensitivity reaction. In such patients, the ELISpot assay is considered a more robust method of diagnosing tuberculosis. We present a case which illustrates that ELISpot can be negative in mycobacterial disease. A 51 year old Jamaican housekeeper, living in the UK for the past 45 years, presented with a 5-month history of a productive cough, shortness of breath and fatigue. She had a 10 year history of seropositive rheumatoid arthritis which was well controlled with methotrexate and etanercept, an anti-tumour necrosis factor (TNF) biologic. She had previously received another anti-TNF drug, infliximab, to which she developed secondary loss of response after 3 years of treatment. Prior to commencing anti-TNF therapy, she was screened for latent tuberculosis and found to have a negative TST and chest radiograph. She was an ex-smoker with a 15 pack-year history. On examination, there was no lymphadenopathy, finger clubbing or focal respiratory findings. The rheumatoid arthritis was inactive. Blood tests showed haemoglobin 12.7 g/dl (11.4–15.0), leukocyte count 4.7 10/l (4.0–11.0), creatinine 62mmol/l (60–110), normal liver function, c-reactive protein 8mg/l (0–10) and erythrocyte sedimentation rate 79 mm/h (1–12). A chest radiograph showed extensive rightsided intra-alveolar and left mid-zone shadowing (Figure 1A). Following treatment with clarithromycin and amoxicillin there was no clinical improvement. A computerised tomography scan of the chest showed patchy areas of ground-glass opacity with traction dilatation of the small airways (Figure 1C). There were small volume pre-tracheal, aortic, pulmonary and right hilar lymph nodes. In view of the clinical presentation in a lady on anti-TNF, a diagnosis of tuberculosis was considered. The ELISpot assay was negative. Sputum microscopy for acid-fast bacilli (AFB) was negative on three occasions. However, sputum culture identified AFB that proved to be Mycobacterium fortuitum. Etanercept was discontinued and the patient was treated with 14 days of amikacin followed by co-trimoxazole and moxifloxacin. A repeat sputum culture at 1 month was negative and a chest radiograph at 4 months showed resolution