Cold agglutinin disease revisited: a multinational, observational study of 232 patients.

We retrospectively studied 232 patients with cold agglutinin disease (CAD) at 24 centers in 5 countries. In Norway and a northern region of Italy, the study was close to being population-based. For the first time, we demonstrate fourfold differences between cold and warmer climates regarding prevalence (20 vs 5 cases/million) and incidence (1.9 vs 0.48 cases/million per year). Mean baseline hemoglobin level was 9.3 g/dL, but 27% had hemoglobin <8 g/dL. Identification of typical features of CAD-associated lymphoproliferative disorder in the bone marrow was greatly increased by centralized biopsy assessment. CAD seems to be associated with a slightly increased risk of venous thrombosis. This work includes a follow-up study of therapies, focusing on the long-term outcomes of the rituximab plus bendamustine and rituximab plus fludarabine regimens. Rituximab plus bendamustine therapy resulted in responses in 35 (78%) of 45 patients; 24 (53%) achieved complete response. Interestingly, these rates were still higher than observed in the original (2017) prospective trial, and we also found a shift toward deeper responses with time. This is explained by the prolonged time to response seen in many patients, probably related to long-lived plasma cells. In patients responding to rituximab-bendamustine, median response duration was not reached after 88 months, and estimated 5-year sustained remission was 77%. The regimen appeared safe regarding late-occurring malignancies. Rituximab plus fludarabine therapy seems to carry a higher risk of long-term adverse effects.

A man in his twenties with fever and severe abdominal pain below the right costal margin. / En mann i 20-årene med feber og sterke magesmerter under høyre kostalbue.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystem disorder characterised by chronic rhinosinusitis, asthma, and pronounced peripheral blood eosinophilia. The most commonly involved organ is the lung. However, EGPA can affect any organ system, including the cardiovascular, gastrointestinal, renal, and central nervous systems. CASE PRESENTATION: A previously healthy 24-year-old man was admitted to the hospital with fever and abdominal pain. He was treated with antibiotics due to suspicion of cholangitis, but his general condition did not improve. He was then given corticosteroids 1 mg/kg x 1 for suspected hypereosinophilic syndrome because of peripheral blood eosinophilia. The corticosteroids improved his condition. After a few days, however, he developed headache, paresis and impaired consciousness. CT cerebral venography revealed haemorrhaging secondary to cerebral venous sinus thrombosis. The patient developed brain herniation and died. Autopsy revealed that he suffered from EGPA. INTERPRETATION: Our patient had an unusual presentation with fever and abdominal pain. After the onset of fever and general symptoms, his vasculitis took an aggressive course. He did not have asthma, sinusitis, or allergies. According to the literature, about 96-100 % of EGPA cases are associated with asthma. Because EGPA is a rare disease, which can have a very serious course, increased knowledge and awareness of the condition is important to achieve early diagnosis and optimal treatment.

Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial.

Primary chronic cold agglutinin disease (CAD) is a well-defined clinicopathologic entity in which a bone marrow clonal B-cell lymphoproliferation results in autoimmune hemolytic anemia and cold-induced circulatory symptoms. Rituximab monotherapy and fludarabine-rituximab in combination are documented treatment options. In a prospective, nonrandomized multicenter trial, 45 eligible patients received rituximab 375 mg/m2 day 1 and bendamustine 90 mg/m2 days 1 and 2 for 4 cycles at a 28-day interval. Thirty-two patients (71%) responded; 18 (40%) achieved complete response (CR) and 14 (31%) partial response (PR). Among 14 patients previously treated with rituximab or fludarabine-rituximab, 7 (50%) responded to bendamustine-rituximab (3 CR and 4 PR). Hemoglobin levels increased by a median of 4.4 g/dL in the complete responders, 3.9 g/dL in those achieving PR, and 3.7 g/dL in the whole cohort. The 10th percentile of response duration was not reached after 32 months. Grade 3-4 neutropenia occurred in 15 patients (33%), but only 5 (11%) experienced infection with or without neutropenia. Thirteen patients (29%) had their dose of bendamustine reduced. In conclusion, bendamustine-rituximab combination therapy is highly efficient, sufficiently safe, and may be considered in first line for patients with CAD requiring therapy. The trial was registered at www.clinicaltrials.gov as #NCT02689986.

Pain and bleeding associated with trephine biopsy.

The study objectives were to determine the intensity and duration of pain, factors that may influence pain experience during and after trephine biopsy, and to assess bleeding and infectious complications related to the procedure. Patients scheduled for trephine biopsy were recruited to the study. Local anesthesia was applied in all patients. Pain intensity was recorded twice daily by the patients using the numeric rating scale (NRS). Bleeding was graded into four grades. Median age of 184 patients was 63 yr. Maximum NRS level was measured at time of biopsy (T0); 167 (91%) patients experienced pain at T0. Median (Q1:Q3) NRS was 3 (1; 5). Median duration of pain was 36 h. Fourteen patients reported pain for more than 7 d. Significant inverse correlation was found between NRS at T0 and age. Pain duration at rest correlated with NRS at T0 and age, while pain duration in activity correlated with NRS at T0, age, and with body mass index (BMI). Mild and moderate bleeding at T0 occurred in 97 (54%) and 18 (10%) patients, respectively; no severe bleeding or infectious complications were registered. Secondary bleeding occurred in two patients; both required hospitalization. In conclusion, the study shows that despite the application of local anesthetic, more than 50% of the patients experienced pain of ≥ 3 points. Procedure-related bleeding is mild to moderate and managed by local pressure only.

[High-dose treatment with autologous stem cell support in a Norwegian region]. / Høydosebehandling med stamcellestøtte i Midt-Norge.

BACKGROUND: The introduction of high-dose treatment with autologous stem cell support (HMAS) in Norwegian regional hospitals in the early 1990s was controversial. Concerns that low numbers of patients would lead to unacceptably low quality were expressed. MATERIAL AND METHODS: We present treatment results in the health region of Middle Norway, based on nearly 10 years of experience and 100 treated patients. Myeloma results are compared to the results from other Norwegian regional hospitals. RESULTS AND INTERPRETATION: Overall survival for multiple myeloma after HMAS (median 6.8 years) was not significantly different in middle Norway compared to the rest of the country, and comparable with published results. Treatment-related mortality was low (1.2%). Results and complications in malignant lymphoma, breast cancer or germ cell tumours are described. HMAS can be satisfactorily given in a regional hospital with relatively few patients.

Hyperferritinemia is associated with insulin resistance and fatty liver in patients without iron overload.

OBJECTIVE: During the last 10 years we have experienced an increasing number of referrals due to hyperferritinemia. This is probably due to increased awareness of hereditary hemochromatosis, and the availability of a genetic test for this condition. Most of these referred patients were over-weight middle-aged men with elevated ferritin levels, but without the hemochromatosis-predisposing gene mutations. We evaluated the relationship between hyperferritinemia and the metabolic syndrome in 40 patients. METHODS: Forty consecutive patients referred for hyperferritinemia were investigated. The examination programme included medical history, clinical investigation and venous blood samples drawn after an overnight fast. This resulted in 34 patients with unexplained hyperferritinemia, which were further examined. Liver biopsy was successfully performed in 29 subjects. Liver iron stores were assessed morphologically, and by quantitative phlebotomy in 16 patients. RESULTS: The majority of the patients had markers of the metabolic syndrome, and 18 patients (52%) fulfilled the IDF-criteria for the metabolic syndrome. Mean body mass index was elevated (28.8+/-4.2), mean diastolic blood pressure was 88.5+/-10.5 mmHg, and mean fasting insulin C-peptide 1498+/-539 pmol/l. Liver histology showed steatosis and nuclear glycogen inclusions in most patients (19 out of 29). Only four patients had increased iron stores by histology, of which two could be explained by alcohol consumption. Fourteen of 16 patients normalized ferritin levels after phlebotomy of a cumulative blood amount corresponding to normal iron stores. Ferritin levels were significantly related to insulin C-peptide level (p<0.002) and age (p<0.002). CONCLUSION: The present results suggest that liver steatosis and insulin resistance but not increased iron load is frequently seen in patients referred for suspected hemochromatosis on the basis of hyperferritinemia. The ferritin level seems to be positively associated to insulin resistance.

[Lead poisoning--a case report]. / Blyforgiftning--en kasuistikk.

Lead poisoning may cause irreversible health defects, including anaemia, central nervous system problems and various organ defects. We describe a patient with lead poisoning. A 54-year-old woman was admitted to hospital with anaemia and unspecific gastrointestinal symptoms. Peripheral blood smear and bone marrow aspirate showed basophilic stippling of erythrocytes suggestive of lead poisoning, which was confirmed by high concentrations of lead in her blood. The lead source was the glazing of a ceramic wine jug. Chelating therapy was started. Haemoglobin was normalised; the patient returned to work after nine months. Correct diagnosis and treatment can prevent serious health problems caused by lead poisoning.

[Lead poisoning--an overview]. / Blyforgiftning--en oversikt.

MATERIAL AND METHODS: We present a review of the history, pathophysiology, diagnosis and treatment of lead poisoning based on relevant literature. RESULTS AND INTERPRETATION: The human body does not metabolize lead, and lead accumulation may cause organ failure. Lead poisoning may cause serious health defects, including anaemia, central nervous system problems and various organ defects. Sources of lead may be found in the home as well as in the workplace or elsewhere in our environment, but lead poisoning is an infrequent condition. Prevention is important, but manifest lead poisoning can be treated effectively.