Unraveling the mystery of fever of unknown origin: a remarkable journey towards the diagnosis of peripheral T-cell lymphoma-T follicular helper type: A rare case report.

INTRODUCTION: Fever of unknown origin (FUO) remains one of the most challenging clinical conditions. It demands an exhaustive diagnostic approach, considering its varied etiologies spanning infectious, autoimmune, inflammatory, and malignant causes. PATIENT CONCERNS: This report shows the journey of diagnosing a 28-year-old male who presented with persistent fever and lower-extremity weakness over 9 months. Despite seeking care at multiple hospitals, a definitive diagnosis remained elusive. DIAGNOSIS: The patient underwent a series of evaluations in various specialties, including gastroenterology, infectious diseases, rheumatology, hematology, and cardiology. Multiple tests and treatments were administered, including antiviral therapy for hepatitis B and antibiotics for suspected infections. INTERVENTIONS: After an initial misdiagnosis and unsuccessful treatments, a positron emission tomography-computed tomography scan and lymph node biopsy ultimately led to the diagnosis of peripheral T-cell lymphoma-T follicular helper type (PTCL-TFH) lymphoma. The patient was referred to the hematology clinic and initiated on CHOEP (cyclophosphamide, vincristine, etoposide, and prednisone) chemotherapy. OUTCOMES: The patient showed a positive response to CHOEP therapy, as indicated by a posttreatment positron emission tomography-computed tomography scan. He reported a significant improvement in his quality of life. Additional rounds of the same regimen were planned to further manage the lymphoma. CONCLUSION: This case emphasizes the importance of a comprehensive and persistent diagnostic approach in managing FUO. Initially, the focus on infectious causes led to extensive treatments, but the disease's progression and complications shifted attention to other specialties. The eventual diagnosis of PTCL-TFH lymphoma highlights the significance of advanced imaging techniques and multidisciplinary collaboration in uncovering elusive diagnoses. Thorough surveillance, timely reassessments, and repeated testing can uncover definitive changes critical for diagnosis. PTCL-TFH lymphoma, although rare, should be considered in the differential diagnosis of FUO, especially when initial evaluations are inconclusive.

Prospective randomized open-label multicenter phase I/II dose escalation trial of visilizumab (HuM291) in severe steroid-refractory ulcerative colitis.

BACKGROUND: Visilizumab is a humanized IgG(2) monoclonal anti-CD3 antibody. We evaluated its safety and dose response in severe intravenous steroid-refractory ulcerative colitis (UC). METHODS: In all, 104 patients were treated. In Stage I, 73 patients were randomly assigned to receive intravenous visilizumab 5, 7.5, 10, or 12.5 microg/kg/day for 2 consecutive days. In Stage II, 33 patients received visilizumab at the optimal clinical dose (OCD) of 5 microg/kg/day for 2 days. Symptomatic response and remission were defined by the modified Truelove-Witts severity index. Clinical response and remission were defined by the Mayo score. RESULTS: The rates of symptomatic response at day 15 in the 5, 7.5, 10, or 12.5 microg/kg dose groups were 71%, 70%, 50%, and 61%, respectively, in Stage I and in 54% in Stage II. The symptomatic remission rates were 35%, 5%, 22%, and 11% in Stage I and 18% in Stage II. The rates of clinical response at day 30 in the 5, 7.5, 10, or 12.5 microg/kg dose groups were 71%, 65%, 50%, and 67%, respectively, in Stage I and 55% in Stage II. The clinical remission rates were 6%, 5%, 0%, and 11% in Stage I and 6% in Stage II. All patients experienced adverse events. Serious adverse events included abdominal abscess, cytomegalovirus infection, atrial fibrillation, herpes zoster, and esophageal candidiasis. CONCLUSIONS: Treatment with visilizumab induced symptomatic response and clinical response. Results with 5 microg/kg/day were similar to those observed with higher doses.

The "return" of hepatitis B.

There has been a significant advance in the treatment of chronic Hepatitis B virus (HBV) infection and the following drugs were approved for therapy: Conventional interferon (IFN), pegylated interferon alfa-2a (PEG IFN alpha2a), lamivudine, adefovir and entecavir. Compared to nucleoside analogues IFN induces higher rates of sustained remission and HBsAg loss. Conventional IFN in lower doses (1, 5-3 MIU) tiw for 4-6 mo has similar efficacy in comparison to "standard IFN therapy". Longer IFN treatment is a significant factor for long-term remission in HBeAg-negative CHB, but the higher actual IFN dose is not such a factor. PEG IFN is superior to conventional IFN. There is no significant difference between PEG IFN alpha2a at doses 90 mcg/wk and 180 mcg/wk in HBeAg-positive patients. These results provide a rational for further clinical trials with lower doses PEG IFN alpha2a given in prolonged course as maintenance or intermittent treatment. Serious new problems arose after the introduction of nucleoside/nucleotide analogues in clinical practice. The most important ones are drug-resistance and the high rates of relapse after treatment discontinuation. Therapy should only be recommended if the expected benefit exceeds significantly the abstain from treatment. The choice of therapy should take into account the patient's age, co-morbidity, severity of liver disease and the risk of drug-resistance. New antivirals significantly suppress HBV-replication, but have no effect on cccDNA in hepatocytes, and after the treatment discontinuation viral relapses occurs. At the present level of knowledge it is impossible "to eradicate the virus" The realistic treatment goal is to achieve durable response by clearance of HBeAg, sustained decrease of serum HBV DNA levels, normalization of ALT, improvement of liver histology and stopping of liver fibrogenesis. The competition between IFN based therapy and nucleoside or nucleotide analogues still remains. IFN can cure the liver disease while nucleotide analogues only suppress the viral replication during therapy and can reduce the liver fibrosis. Treatment should be prolonged for 24-mo or longer by using maintenance or intermittent treatment course with the lowest effective IFN and PEG IFN doses. Nucleoside/nucleotide analogues are a promising treatment option, but additional data for treatment duration and long-term post-treatment outcome are necessary.