We reported the case of a 72-year-old woman for whom a history of primary tuberculosis infection during childhood was unclear and who presented with tuberculous arthritis during the setting of 177Lu-DOTATATE PRRT. Initially, this patient had abdominal pain at diagnosis and a contrast-enhanced computer tomography (CE-CT) lead to the diagnosis of primary pancreatic NET with synchronous liver metastases (grade 2 and Ki-67 15% at biopsy). The patient received a first-line treatment using somatostatin analogues without significant tumor response or improvement of the clinical symptomatology. A second and third line of treatment using chemotherapy (gemcitabine/oxaliplatin followed by capecitabine/temozolomide) only stabilized the disease for less than a year. Indeed, a follow-up FDG PET/CT scan showed a mild metabolic progression in both primary pancreatic tumor and liver metastases. 68 Ga-DOTATATE PET/CT showed high uptake in both primary pancreatic tumor and liver metastases (Additional file 1: Fig. S1 ). Therefore, in agreement with the standard of care and after approval of the dedicated multidisciplinary board, initiation of PRRT using 177Lu-DOTATATE was decided. Patients or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this case report.
PRRT Therapy
The patient received the first cycle (C1) of PRRT with a reduced activity of 5.6 GBq instead of standard 7.4 GBq due to her low body mass index (18 kg/m2) though clinical examination was unremarkable and the blood work was within normal range (Fig. 1). Between the first and second cycle, the patient reported a traumatic fall involving the right elbow and the right ankle with persistent inflammatory pain in the latter. At clinical examination before the second treatment, there was a limping of the right ankle with pain at mobilization and swelling, but no redness nor fever was found. In light of those symptoms, PRRT was postponed until further investigations. Same day blood work showed elevated white cell counts with 13.5 (N > 1.8) G/L for neutrophils (NP), whereas lymphocytes (LP) were below 0.4 (N > 1.5) G/L (Fig. 1). In addition, C-reactive protein (CRP) was elevated at 102 (N < 5) mg/L, but procalcitonin was normal at 0.08 (N < 0.5) µg/L) and blood cultures were negative. Similarly, synovial fluid withdrawal did not show any inflammatory nor cancerous cells nor crystals, and standard ankle and chest X-rays were also negative (Additional file 1: Fig. S2). Thus, the resulting diagnostic was a mono-arthritis of undefined origin ranging from paraneoplastic, chondrocalcinosis, inflammatory rheumatism to insidious infection. Additionally, as the blood work normalized the next day without any treatment (NP: 4.9 G/L and LP: 0.65 G/L, Fig. 1) and in the absence of conclusive clinical sign of active infection, the patient received the second cycle of PRRT with a further reduced activity of 3.8 GBq of 177Lu-DOTATATE with good clinical tolerance. Clinical assessment before injection of the third injection of 177Lu-DOTATATE was normal, and the patient did not present any pain at the clinical examination of her right ankle. Between the 3rd and 4th cycle of PRRT, the patient was again investigated for the same pain of the right ankle, which was explored without conclusive results leading to a delay in initiating the 4th injection of 177Lu-DOTATATE by 4 weeks. At the time of C4, the blood work was satisfactory though a slight Lymphopenia was seen 1.4 G/l (Fig. 1), and the treatment was carried out with injection of half the standard activity of 177Lu-DOTATATE with a good clinical tolerance.
Interestingly, though all investigations remained negative during the course of PRRT, post-injection planar scintigraphy at 48 h showed from the second cycle an increasing mild uptake of the right angle (Fig. 2). In contrast, on additional SPECT/CT imaging, there was a continued decrease in Lu177-DOTATATE uptake in NET lesions, particularly in the pancreatic tumor and liver metastases (Fig. 3). Ultimately, the patient presented with a good response on the 68 Ga-DOTATATE PET/CT scan done 4 months after the end of PRRT (Additional file 1: Fig. S1).
However, two months after the end of PRRT, the patient experienced once again an acute pain in the right ankle. Blood tests, ankle ultrasound and CT scan were suspicious for an active infection, with the latter showing bone erosions in favor of an aggressive process. The patient underwent an arthroscopy with multiple biopsies, an arthrotomy of the medial malleolus and a curettage of the infection site. Biopsies and subsequent bacterial cultures led to retain the diagnosis of a chronic tuberculosis infection with mycobacteria tuberculosis of the right ankle. As tuberculosis was suspected, a thoracic CT scan was performed and did not show any pulmonary sign of the disease. After a pneumology referral, a long-term anti-tuberculosis treatment using the four-drug fixed-dose combination regimen RIMSTAR® (9), combined with a B6 vitamin substitution, was started.