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The INBUILD trial investigated the efficacy and safety of nintedanib versus placebo in patients with progressive fibrosing interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF). We aimed to establish the effects of nintedanib in subgroups based on ILD diagnosis.

A 72 year old man was diagnosed with chronic myelomonocytic leukaemia (CMML) according to the FAB group classification. He presented with symptoms of anaemia, urinary frequency, hesitancy, and nocturia. He was later admitted with acute urinary retention and acute renal failure, which resolved with treatment. A transurethral resection of the prostate was performed. Histological examination showed fibromuscular hyperplasia with dense infiltration by myelomonocytes which stained positively with chloroacetate esterase; immunohistochemical staining was positive for lyso-zyme, CD43, CD45, and CD68. Following treatment with oral etoposide he transformed to acute myeloid leukaemia and eventually died. Myelomonocytic infiltration of the prostate has not been reported before. This case extends the spectrum of disease previously recognised in CMML.

Alemtuzumab, a licensed treatment for relapsing multiple sclerosis (MS) has proven efficacy in reducing relapse rates and improving disability outcomes. However, despite these beneficial effects, approximately 50% of patients develop secondary autoimmune disease (AID). The constellation of AIDs reported thus far encompasses Th2, B cell/antibody-driven pathologies including thyroid autoimmunity, idiopathic thrombocytopenic purpura and Goodpasture’s syndrome. In contrast to this, we present two patients with MS treated with alemtuzumab whom subsequently developed systemic sarcoidosis, a Th1 mediated disease. The first case presented with chest pain and shortness of breath 8 years after the initial infusion of alemtuzumab with computed tomography (CT) of the thorax demonstrating widespread lymphadenopathy and peri-bronchovascular nodularity. Biopsy of a cervical lymph node demonstrated non-caseating granulomas with the changes considered consistent with sarcoidosis. Four years after initial infusion, the second case was found to have incidental right-sided hilar lymphadenopathy following routine Xray with CT demonstrating widespread lymphadenopathy. Subsequent sub-carinal lymph node core biopsy demonstrated granulomatous inflammation in association with a raised serum ACE and a diagnosis of sarcoidosis was made. To our knowledge, these are the first reported cases of Th1-cell mediated secondary autoimmunity following alemtuzumab for MS and we speculate on the possible immunological mechanisms to account for this.