Methotrexate dosage as a source of bias in biological trials in rheumatoid arthritis: a systematic review.

OBJECTIVES: To evaluate if optimal dose of either oral or injectable regimens of methotrexate (MTX) of 25 mg/week was used in the comparator arms of studies comparing biologic drugs with MTX in rheumatoid arthritis (RA). METHODS: A systematic literature search was carried out in MEDLINE, EMBASE and the Cochrane Library databases for randomised controlled trials comparing biologics with MTX in RA. A systematic review was performed among studies that met predefined criteria focusing on assessment of dose of MTX used in the comparator arm. Study authors were contacted when necessary. Study quality was assessed. RESULTS: A total of 3276 references were identified and 13 trials were included. We obtained maximal dose and regimen for all. The maximal dose of MTX used in the comparator arm of the trials was no more than 20 mg/week in any trial and for all but one trial, MTX was given orally and not by injection. The trial that used an injectable form reached a maximum of 15 mg/week. CONCLUSIONS: A suboptimal dose of MTX was used in biological clinical trials performed in RA, particularly regarding route of administration. This may have biased findings in favour of biological agents.

Adult Onset Henoch-Schönlein Purpura: Case Report and Review of Literature.

Henoch-Schönlein purpura (HSP) is an IgA mediated small-vessel vasculitis, more common in children than adults. We present the case of a 37-year-old male who presented with complaints of nausea, vomiting, abdominal pain, purpuric rash over lower extremities, and migratory polyarthralgia five days after being treated with antibiotics for bronchitis. In addition to the abdominal pain, he developed diarrhea and colonic biopsy findings were suggestive of inflammatory bowel disease (IBD). Skin biopsy revealed leukocytoclastic vasculitis with direct immunofluorescence studies (DIF) staining of IgA deposition confirming the diagnosis of HSP. The clinical features of cutaneous eruption with abdominal complaints can be seen with either HSP or IBD; however the specific skin biopsy findings on DIF can distinguish between the two disease processes. Though HSP is primarily seen in the pediatric population, it is a disease process that must be considered in adults presenting with vasculitic skin rashes and abdominal complaints.

Severe heart failure after bortezomib treatment in a patient with multiple myeloma: a case report and review of the literature.

BACKGROUND: Bortezomib is a novel, first-in-class peptide which reversibly inhibits the proteasome and is Food and Drug Administration approved for the treatment of multiple myeloma, non-Hodgkin lymphoma, Waldenström's macroglobulinemia, and systemic light chain amyloidosis, among others. CASE REPORT: Very few cases of bortezomib-induced cardiotoxicity have been reported in the literature, and most of them have been confounded by the previous use of anthracyclins. We reviewed the case of a 56-year-old woman with a medical history of well-controlled hypertension who was newly diagnosed with International Staging System stage I multiple myeloma. She presented with new symptoms of exertional dyspnea, paroxysmal nocturnal dyspnea, and orthopnea after a 4th cycle of a bortezomib/dexamethasone-based chemotherapy. Clinical examination was consistent with heart failure. 2-D echocardiogram showed an left ventricular ejection fraction of 25%, abnormal wall motion, severe eccentric mitral regurgitation, and moderate pericardial effusion. Coronary angiogram showed normal coronaries, and cardiac magnetic resonance did not show delayed gadolinium enhancement. CONCLUSION: We reviewed the possible mechanisms involved in cardiotoxicity caused by bortezomib, and the diagnostic methods and importance of early identification of this adverse event. Differential diagnoses such as cardiac amyloidosis and viral myocarditis are also discussed. To our knowledge, this is the first case where pericardial effusion and mitral regurgitation were described after bortezomib treatment.

Superior vena cava syndrome caused by colon adenocarcinoma metastasis: a case report and review of literature.

Superior vena cava (SVC) syndrome is a critical medical condition that usually results from compression of the SVC by an intrathoracic mass. The majority of contemporary etiology of SVC syndrome are related to mediastinal malignancies and/or to the presence of intravascular devices. Rarely, SVC syndrome has been associated with intraluminal metastasis to this vessel. We describe an unusual case of an 88-year-old woman with stage IIA colon carcinoma diagnosed seven years earlier that was treated with surgical resection, who presented with classical signs and symptoms of SVC syndrome. Imaging studies confirmed the presence of an extensive mass in the SVC and intravascular biopsies showed metastatic colon cancer. She was treated with palliative radiotherapy with good clinical response, remaining asymptomatic eight months after the documentation of metastatic disease. To our knowledge this is the second published case of colorectal adenocarcinoma with intravascular metastasis to the superior vena cava causing SVC syndrome. We discuss the different etiologies and management of this syndrome, and encourage physicians to consider intraluminal metastasis as one of the etiologies.

Gitelman syndrome and pregnancy.

Gitelman syndrome (GS) is an autosomal-recessive condition characterized by hypokalemia, hypomagnesemia and hypocalciuria. Very little information is available in the literature to guide the management of pregnant patients with GS. We report a case of a 27-year-old woman with GS who became pregnant and despite persistent hypokalemia and hypomagnesemia during pregnancy and labor, had a successful maternal and fetal outcome.