1.\u2003TIF1-γ associated dermatomyositis

Abstract

Abstract Introduction This is a case of a patient presenting at the age of 39 with dermatomyositis. Subsequent investigations revealed her to have a TIFI-γ antibody and a metastatic colon adenocarcinoma. She was initially steroid responsive and her malignancy simultaneously responded to chemotherapy. A relapse of her malignancy was preceded by a flare in her dermatomyositis which proved to be non-responsive to steroids and further chemotherapy. Case description The patient presented to rheumatology at the age of 39 with a few-week history of a photosensitive rash on her face, upper chest and hands. This was followed by rapidly progressive symmetrical proximal and truncal muscle weakness and pain. She described dysphagia to solids and shortness of breath on exertion. She had a very short history of weight loss, attributed to reduced oral intake. She had no relevant past medical history and was taking no medications. Examination revealed power of 3/5 in both upper and lower limbs, a heliotrope rash with Gottrons papules with normal cardiovascular and respiratory examinations. CK at presentation was 3709. Haematology and biochemistry was otherwise normal. MRI thighs showed extensive myositis. ANA was positive with a positive TIFI-γ antibody. CT scan showed a proximal sigmoid mass with local and mediastinal lymphadenopathy and a 6mm lung nodule. Histology from a mediastinal node confirmed a metastatic adenocarcinoma. Initially, the patient was treated as an autoimmue dermatomyositis with pulsed IV methylprednisolone followed by high dose prednisolone. She responded rapidly both clinically and biochemically to steroids. Following the diagnosis of malignancy, she underwent a hemicolectomy from which she made an uneventful recovery. She then completed 12 cycles of oxaliplatin and 5FU chemotherapy, with interval CT scanning showing good partial response to treatment and she returned to work. One month after completing chemotherapy, whilst still taking prednisolone her rash reoccurred. This rapidly progressed despite an increase in her steroids and quickly became associated with weakness and further shortness of breath. CT showed a progression of her malignancy with carcinomatosis lymphangiitis. She received one cycle of Irinotecan before being admitted with neutropenic sepsis and progression of her cancer. At this time she decided to withdraw all treatment and died shortly afterwards at the age of 40, 18 months after her initial presentation. Discussion TIF1-γ antibodies were first identified in 2006 and are involved in cell regeneration, apoptosis and innate immunity. High levels of TIFI-Y are found in the nuclei of regenerating myofibres. They are associated with dermatomyositis and are found in between 13 – 31% of adults and 22 – 29% of children. There is a strong association with malignancy in those aged over 39 (positive predictive value of 58%, sensitivity 78%, specificity 89%). There are no case reports of malignancy associated with TIF1- Y antibodies in patients under the age of 39. Malignancy typically presents early in the course of dermatomyositis, being diagnosed at presentation or within 8 months. There are case reports of TIF1- Y antibodies co-existing with Mi2 antibodies, increasing malignancy risk. In younger patients this association with cancer is not seen but the antibody is associated with skin ulceration and chronic disease. It is hypothesised that differences in HLA regions and protein conformation may account for these different phenotypes. Patients typically have a lower CK and there is a higher incidence of amyopathic dermatomyositis compared with other myositis specific antibodies. Our patient was at the lower end of the risk spectrum for malignancy and had no localising symptoms for this. She was initially very steroid responsive, which again lowered our threshold for suspicion of malignancy. Indeed, her CT was requested on the basis of shortness of breath looking for interstitial lung disease rather than anything more sinister. Key learning points TIF1-γ antibodies have a strong association with malignancy in patients over the age of 39. Clinicians should have a high index of suspicion even in the absence of symptoms of malignancy. Malignancy associated dermatomyositis can be steroid responsive. A relapse of dermatomyositis should raise suspicion for a relapse of malignancy. Conflicts of interest The authors have declared no conflicts of interest.