The 22-year-old male patient presented at age 14 years with epistaxis related to severe thrombocytopenia. Immune thrombocytopenic purpura (ITP) was diagnosed and he was initially treated with high doses of prednisone. Prior to immunosuppression, his immunoglobulins had been measured and were found to be in the normal range (IgG 8.8 g/l, nr 7-14). Following initiation of steroid therapy he became hypogammaglobulinemic (IgG 4.3 g/l).
Once the severe hypogammaglobulinemia was identified, he was treated with IVIG (2 g/kg), with the added expectation the immunomodulatory doses of IVIG would reduce his risk of infections as well as potentially benefitting his ITP. He then developed Evans syndrome with autoimmune haemolytic anaemia, in addition to the ITP. When reviewed in 2011, he was Cushingoid from corticosteroids. He responded to this regimen and the prednisone was tapered to 10 mg daily and stopped.
He was well until 2013 when his ITP relapsed. On this occasion he did not respond to high dose prednisone, vincristine, cyclosporine, cyclophosphamide or rituximab. Due to ongoing cytopenias he underwent a splenectomy in 2014. Histology revealed the presence of splenic granulomas. Although the splenectomy was not successful, he remitted with eltrombopag in 2014.
He remained well until early 2017 when he developed diplopia consequent to bilateral cranial VI nerve palsies. He had headaches, fever and signs of meningism. Lumbar puncture showed an elevated CSF opening pressure but protein and other cellular parameters were normal. CSF bacterial culture, fungal antigen tests and viral PCR studies excluded infection. MRI of the brain showed an ill-defined enhancing area around the anterior pons.
He had widespread lymphadenopathy including mediastinal and abdominal lymphadenopathy on MRI scanning. Excision biopsy of a left inguinal lymph node showed the presence of discrete non-caseating granulomas, reactive follicles and overall normal lymph node architecture (Fig. 1a). Plasma cells were present although slightly reduced compared to a normal control (Fig. 1b, c). His serum angiotensin converting enzyme (ACE) level was normal. 
The following week he developed increasing gait instability and was readmitted to hospital. Repeat CSF examination again showed an increased opening pressure (23 cm) and a raised protein level. The cell count and glucose were again normal. A repeat MRI scan of brain and spine revealed enhancing lesions in the cauda equina roots suggestive of granulomatous inflammation (Fig. 2). The previous pontine lesion had resolved. Given the location of inflammation, a biopsy was not possible. Nerve conduction tests of the lower limbs were consistent with nerve root involvement. Several months after starting steroids, a gallium PET scan showed enhancing lesions of the lacrimal gland. 
PCR studies of the CSF and blood were negative for toxoplasma and tuberculosis (TB), the two main infectious differential diagnoses for granulomatous infections in New Zealand. He had not recently travelled internationally. He had a good response to IV methylprednisolone (1 g) treatment with resolution of headaches and fever, as well as improvement in gait. He was able walk unaided. The improvement was reflected in the blood tests, with the CRP decreasing from 69 to 7 mg/l within a week, and improving cytopenias. He was placed on low dose oral prednisone and mycophenolate with iv methylprednisolone 1 g every 2 weeks.
In mid-2018 when the immunosuppression was lifted, his IgG increased from 3.0 g/l to 8.8 g/l (Fig. 3) and the previously decreased IgA and IgM also normalised. Shortly afterwards he developed progressive renal impairment with a creatinine clearance of 36 ml/min. Renal biopsy showed 18/42 sclerosed glomeruli. No granulomas were identified. He was recommenced on Mycophenolate (MMF) and low dose prednisone. There was insufficient time to undertake vaccine response or detailed immunophenotyping studies before the immunosuppression was urgently recommenced. Over the following 6 months the creatinine clearance increased to 66 ml/min. The family has undergone whole exome sequencing for diagnosis and gene discovery but no causative mutation was identified.