Susceptibility to mycobacterial infection in a young man with a hypoglossal nerve palsy: the hunt for an immunological defect

A 17-year-old boy presented with a four-week history of neck pain, difficulty chewing and deviation of his tongue to the right. On examination there was tenderness of the mid-cervical spine and a right XII nerve palsy. A 6 cm lesion was noted over the left deltoid (Figure 1). There was no lymphadenopathy or splenomegaly. Blood tests were normal apart fromESR 44 mm/h andCRP 83mg/L. Cervical spine X-rays showed increased space between the odontoid peg and the arch of C1. CT of the neck revealed destruction of the basisphenoid, clivus and right occipital condyle, with craniocervical instability. The cervical spine was immobilized with a hard collar pending halo fixation. Gadolinium-enhanced MRI showed a T1 signal abnormality around the hypoglossal nerve and involving the anterior foramen magnum and the right side of the C1 vertebra. Tc bone scintigraphy revealed increased uptake in the sacrum, right iliac crest, right eighth rib and left acetabulum. Following BCG vaccination four years previously the patient developed a chronic 6 cm discharging lesion at the inoculation site. This was biopsied one year prior to his presentation with neck pain. Histology demonstrated necrotizing granulomas and BCG was cultured. He defaulted follow-up and failed to complete antimycobacterial therapy. The right iliac crest was biopsied and histology revealed non-caseating granulomatous inflammation. Although staining for AAFB was negative, rifampicin, isoniazid and ethambutol were commenced for presumed disseminated BCG. Culture confirmed BCG at 7 weeks, sensitive to rifampicin, isoniazid and ethambutol, resistant to pyrazinamide. The patient’s neck pain and XII nerve palsy resolved and his cutaneous lesion began to heal. A bone scan at 5 months showed reduced uptake in the right iliac crest and no additional abnormality. CT of the cervical spine at 9 months indicated fusion of the right occiput to C1. Triple therapy was continued for 1 year followed by rifampicin+ isoniazid for a further year. Nuclear magnetic spectroscopy 1 year after discontinuing therapy showed improvement and the patient remains well. He had no history of infection with bacteria, viruses or fungi, suggesting an isolated predisposition to mycobacteria. He was HIV-negative with normal immunoglobulin levels, IgG subclasses, complement levels and normal levels of specific antibodies to all the childhood vaccinations. Lymphocyte subsets showed generalized depression, attributed to disseminated infection, but normal percentages. Major histocompatibility complex class I & II expression was normal. He had normal adenosine deaminase and purine nucleoside phosphorylase levels, normal lymphocyte proliferative responses, normal neutrophil oxidative burst function and normal Toll-like receptor (TLR) 4 and TLR 7/9 screening by CD62L shedding assay. DECLARATIONS