Rheumatology Advances in Practice | 2021
Rapid weight loss in a patient with anti-synthetase syndrome treated with sodium–glucose cotransporter 2 inhibitors and corticosteroids
Abstract
DEAR EDITOR, Sodium–glucose cotransporter 2 (SGLT2) inhibitors, which block glucose reabsorption in the proximal tubules, have been used to treat type 2 diabetes mellitus (T2DM) [1]. Recently, the usefulness of SGLT2 inhibitors in patients with heart failure has also been reported [2]. Thus, SGLT2 inhibitors have become new therapeutic options for T2DM and heart failure. Body weight loss is a side effect of SGLT2 inhibitors [3]. Although body weight is not a serious problem in clinical practice, it can be problematic in specific patients. A 71-year-old Japanese woman was admitted to our hospital because of dyspnoea. One year before admission, she was diagnosed with idiopathic pulmonary fibrosis in another hospital, where her pulmonary function remained relatively steady. Her family did not want her to undergo detailed examination; therefore, she was diagnosed with low-activity interstitial lung disease (ILD) and did not receive medication. Four months before admission, her dyspnoea worsened. On further evaluation, she tested positive for serum anti-aminoacyl-transfer RNA synthetase (anti-ARS) antibodies, suggesting CTDassociated ILD (CTD-ILD). Therefore, she was admitted to our hospital for possible CTD-ILD. She had a medical history of hypertension, T2DM and atrial fibrillation. She received empagliflozin (10 mg/day), telmisartan, amlodipine and warfarin. On admission, her vital signs were as follows: body temperature, 35.5 C; blood pressure, 96/64 mmHg; pulse, 96 beats/min; respiratory rate, 16 breaths/min; and peripheral oxygen saturation, 96% in ambient air. Her body weight and BMI were 61.3 kg and 23.1 kg/m, respectively. Physical examination revealed Gottron’s papules and mechanic’s hands. Bilateral digital arthralgia was also observed. On auscultation, fine crackles were heard in the left and right lower lung fields. Neurological examination revealed mild muscle weakness of the neck flexors (grade 5 ) and pectoralis major (grade 4þ/4þ), without weakness of other proximal muscles. Laboratory investigations showed elevated levels of serum CRP (0.89 mg/dl). Serum levels of Krebs von den Lungen and surfactant protein D were significantly elevated (3363 U/ml and 259 ng/ml, respectively). Serum levels of muscle deviation enzymes (creatine kinase, myoglobin and aldolase) were within the normal limits. The ANA titre was 1:40 with a speckled pattern and 1:80 with a cytoplasmic pattern. The ELISA was positive for anti-ARS antibodies; however, the specific type of anti-synthetase syndrome antibody was not detected owing to the unavailability of immunoprecipitation in our institution. Urinalysis revealed glucosuria (4þ), but the blood glucose concentration and haemoglobin A1c were 124 mg/dl and 6.2%, respectively. Based on these, her T2DM was well controlled by empagliflozin. Chest CT revealed non-specific interstitial pneumonia. Skin biopsy showed liquefaction, degeneration, lymphocyte infiltration around small vessels and mucin deposition, consistent with DM. She was diagnosed with anti-synthetase syndromeassociated ILD. She then received a CS treatment (initial dose: methylprednisolone, 48 mg/day) and tacrolimus. Her blood glucose concentration increased to 250 mg/ dl because the CS exacerbated her T2DM. Her body weight decreased rapidly after the initiation of CS therapy, whereas her serum urea nitrogen levels increased. Orthostatic hypotension was also observed. Her rapid body weight loss was probably a side effect of the SGLT2 inhibitor (empagliflozin), accumulated by the CS. Empagliflozin was replaced with an insulin injection. She stopped losing weight, and the serum levels of urea nitrogen decreased after empagliflozin discontinuation (Fig. 1). Patients treated with SGLT2 inhibitors lose 1–3 kg of body weight [4]. This is often recognized as a beneficial side effect of SGLT2 inhibitors [4]. It has been assumed that the weight loss is caused by body water loss owing to osmotic diuresis, fat reduction owing to energy loss through urinary glucose excretion, and hypercatabolism secondary to metabolic adaptations. Accordingly, it was reported that early weight loss until 4 weeks in patients treated with ipragliflozin might be largely related to fluid loss owing to osmotic diuresis, whereas ongoing weight loss until 12 weeks might represent reduction in body fat related to calorie loss [5]. The skeletal muscle mass index reportedly decreased after administration of luseogliflozin [6]. In our case, the serum levels of urea nitrogen were elevated as the patient lost weight, indicating accelerated catabolism. CSs induce hyperglycaemia and hypercatabolism [7]. Thus, we hypothesized that the CS-induced hyperglycaemia increased osmotic diuresis Key message