Chronic use of metamizole: not so safe after all?

Metamizole can be used in both short- and long-term pain relief therapies and has a relatively favourable safety profile compared with classic NSAIDs. Metamizole is also infamous because of its potential fatal adverse drug reaction, agranulocytosis. Although this risk varies, it is estimated to occur in less than one million metamizole prescriptions. We describe a case of a 68-year-old patient who developed leukopenia after using metamizole.

Mucositis not neutropenia determines bacteremia among hematopoietic stem cell transplant recipients.

BACKGROUND: In the 1960s, it was reported that infectious complications were the main cause of fever during neutropenia that followed hematopoietic stem cell transplant (HSCT). More recently, mucositis has become recognized as an important determinant of the inflammatory response and infectious complications. METHODS: The objective of this prospective study was to determine the impact of intestinal mucositis, as measured by plasma citrulline, and neutropenia on the systemic inflammatory response (C-reactive protein) and the occurrence of bacteremia among 2 cohorts of HSCT recipients: 1 composed of 18 patients who had been treated with a myeloablative (MA) regimen (high-dose melphalan) and the other involving 19 patients who had received the non-myeloablative (NMA) regimen (fludarabine and cyclophosphamide). Blood cultures were obtained for surveillance from admission onwards as well as at the onset of fever. RESULTS: The MA regimen induced severe intestinal mucositis manifest by citrullinemia <10 µmol/L, which was accompanied by an inflammatory response, and bacteremia affected 8 (44%) of 18 patients and coincided with the nadir of citrullinemia. By contrast, those who had been treated with the NMA regimen did not develop severe intestinal mucositis, had a moderate inflammatory response, and only 2 (11%) of the 19 patients developed bacteremia. However, both groups experienced profound neutropenia and its duration was significantly longer for those receiving the NMA regimen. CONCLUSION: This study suggests that severe intestinal mucositis, i.e., citrullinemia <10 µmol/L, defines the period of risk of bacteremia better than does neutropenia, and that measuring plasma citrulline may prove useful in deciding who needs empirical antimicrobial therapy and when.

Impact of palifermin on intestinal mucositis of HSCT recipients after BEAM.

The matched-control study failed to show a clinical relevant impact of palifermin on intestinal mucositis, although there was a reduced inflammatory response and less febrile neutropenia among patients who had no bacteraemia.

Citrulline and albumin as biomarkers for gastrointestinal mucositis in recipients of hematopoietic SCT.

Gastrointestinal (GI) mucositis is a common side effect of intense chemotherapy to prepare patients for hematopoietic SCT. Measuring intestinal damage objectively remains difficult, and clinicians often rely on albumin levels as an indicator of GI mucositis, but citrulline might be a more specific marker, which has in the past been shown to correlate with clinical signs of GI mucositis. We evaluated the courses of albumin and citrulline following different conditioning regimens for SCT and studied their relatedness to the subsequent inflammatory response using C-reactive protein. Patterns of albumin and citrulline differed significantly between myeloablative and non-myeloablative conditioning regimens. After myeloablative regimens, decreasing citrulline levels preceded the occurrence of inflammation unlike albumin levels, which decreased thereafter. Albumin levels were greatly influenced by inflammation, confirming it to be a 'negative acute-phase protein', whereas citrulline levels were not. Citrulline appeared to be a better biomarker of GI mucositis than albumin. Measuring citrulline might prove useful in clinical decision making, in identifying GI mucositis, and it would also be of interest to see how it compares with other biomarkers in the setting of acute GI GVHD.

Bacteraemia coincides with low citrulline concentrations after high-dose melphalan in autologous HSCT recipients.

Mucosal damage to the intestines induced by myeloablative conditioning for allogeneic PBSC transplant (PBSCT) can be determined by the concentration of citrulline, which is a functional marker of small intestinal enterocytes. Low citrulline concentrations in blood coincide with and are a response to severe mucosal barrier injury. We treated 29 patients with high-dose melphalan 200 mg/m(2) (Mel-200) to prepare for an autologous PBSCT and collected plasma samples from each patient starting before the myeloablative regimen and three times per week thereafter until discharge. The baseline citrulline concentration was 27.6 mM+/-4.0 (mean+/-95% confidence interval; CI), and citrulline concentrations declined rapidly thereafter reaching a nadir averaging 6.7 mM+/-2.7, 12 days after starting Mel-200. Citrulline concentrations, only increased gradually and were still low (12 mM+/-4) at discharge. A total of 20 patients developed fever, which was associated with bacteraemia in 10 cases. Their mean citrulline concentrations were lower at 5.5 mM+/-1.5 than were those of patients without bacteraemia (10.2 mM+/-3.9). Importantly, neither the number of preceding neutropenic days nor the mean C-reactive protein (CRP) concentration at the onset of fever was different between these two groups. In conclusion, citrulline concentrations rapidly decline after Mel-200 reflecting intestinal mucosal barrier injury. Low citrulline, rather than the duration of neutropenia, is associated with bacteraemia indicating the importance of an intact mucosal barrier in neutropenic patients.

Staging for CLL-type non-Hodgkin's lymphoma reveals a gastrointestinal stromal tumour.

We report a 73-year-old man presenting with fatigue, lymphadenopathy and weight loss. He had no abdominal pain, fever or night sweats. Physical examination revealed a palpable 1.4-cm hard nontender lymph node behind the left sternocleidomastoid muscle and a palpable 2-cm lymph node in the left axilla. Bone marrow examination and excisional biopsy of the lymph node behind the left sterno-cleidomastoid muscle showed a CLL-type non-Hodgkin's lymphoma (CLL-type NHL). Staging by CT scanning revealed, besides axillary and mediastinal adenopathy, an unexpected mass in the stomach. Gastroscopy and pathological evaluation showed a gastrointestinal stromal tumour (GIST) with immunohistochemical staining for CD 34 and CD 117. The patient was treated with imatinib. CLL-type NHL and GIST both tend to occur in middle-aged and older patients. A double-tumour consisting of both these tumours is rare: the incidence is estimated to be 3 per 10 billion people.