以不明原因发热为首发表现的恶性肿瘤69例临床分析

目的探讨以不明原因发热（FUO）为首发表现的恶性肿瘤患者的病因及临床特征。方法回顾性分析我院2000年1月～2007年12月间以FUO为首发表现的69例恶性肿瘤患者的病因、诊断方法和临床表现。结果69例恶性肿瘤患者男女比例为3．06：1,淋巴瘤最多见（占56．5％）,肺癌次之（占24．6％）。多部位穿刺活检有助于淋巴瘤明确诊断,淋巴瘤患者PPD试验阳性率低于结核病,但差异无显著性;89．7％（35／39）的患者有血象下降改变,其中三系细胞均下降比例最高,占36．4％（14／39）,83．9％（26／31）的患者乳酸脱氢酶（LDH）增高。所有肺癌患者均合并有阻塞性肺炎。结论以不明原因发热为首发表现的恶性肿瘤患者中淋巴瘤居首位,肺癌其次,仔细寻找线索有助于明确诊断。     

Fever of unknown origin in older adults

Evaluation of elderly patients who have fever of unknown origin (FUO) requires a different perspective from that needed for young patients. Differential diagnosis often varies with age, and presentation of the disease frequently is nonspecific and symptoms difficult to interpret. Noninfectious diseases are the most frequent cause of FUO in the elderly and temporal arteritis the most frequent specific cause. Tuberculosis is the most common infectious disease associated with FUO in elderly patients. FUO often is associated with treatable conditions in the elderly. Therefore, intensive, accelerated evaluation is necessary, as the lack of physiologic reserve makes this population vulnerable to irreversible changes and functional deterioration.     

Fever of unknown origin caused by adult juvenile rheumatoid arthritis: the diagnostic significance of double quotidian fevers and elevated serum ferritin levels

Fever of unknown origin (FUO) in adults is a commonly encountered clinical problem. Treatable causes of FUO in the adult should be the primary focus of the diagnostic workup. Neoplasms have replaced infectious diseases as being the most common cause of FUO in adults, and collagen vascular diseases are now relatively rare. The most important collagen vascular diseases presenting as an FUO include Takayasu's arteritis, Kikuchi's disease, polymyalgia rheumatica, and adult juvenile rheumatoid arthritis (JRA) (adult Still's disease). There are no specific diagnostic tests for these disorders, which commonly present as prolonged fevers that are not easily diagnosed (i.e., FUO). Adult JRA is a rare but important cause of FUO in adults. Typically, patients with adult Still's disease present with liver/spleen involvement, posi-articular arthritis, ocular involvement, and evanescent salmon-colored truncal rash. An important diagnostic finding in adult JRA is the presence of a double quotidian fever, which occurs in few other disorders. Only visceral leishmaniasis and adult JRA are causes of FUO in adults associated with double quotidian fevers. Highly elevated serum ferritin levels are the most important nonspecific diagnostic finding associated with adult JRA. We present a case of FUO caused by adult JRA presenting with diffuse polyarticular migrating arthritis, evanescent rash, and splenomegaly. The diagnosis of adult JRA was suggested by these findings in association with a double quotidian fever and a highly elevated serum ferritin level. Clinicians should appreciate the diagnostic significance of fever patterns and the diagnostic significance of elevated serum ferritin levels in patients with FUO.     

Aggressive multiple myeloma presenting as mesenteric panniculitis

Mesenteric panniculitis is a rare disease of the bowel mesentery, characterized by tumor-like infiltration by chronic inflammatory cells, fat necrosis, and fibrosis. Reported cases cited clinical presentation ranging from abdominal pain to fever of unknown origin, the majority of which were idiopathic and associated with a benign prognosis. We report the case of a 43-yr-old male who presented with malaise, weight loss, microcytic anemia, and a high erythrocyte sedimentation rate. Radiographic and histological investigations revealed typical features of mesenteric panniculitis. Initial treatment with high-dose oral prednisolone led to rapid and complete resolution of symptomatology, radiographic, and laboratory anomalies. Within 6 months, the patient presented again with anemia, renal failure, and hypercalcemia. A diagnosis of IgA kappa chain myeloma was made. Despite chemotherapy and restoration of normocalcemia, he died from refractory pulmonary edema. This is the first report of a hematological malignancy initially presenting with features of mesenteric panniculitis culminating in an aggressive course and a fatal outcome.     

Fever of unknown origin caused by multiple myeloma: a report of 9 cases

BACKGROUND: Most authorities regard multiple myeloma as a rare cause of fever and not a cause of fever of unknown origin (FUO). OBJECTIVE: To describe a series of patients with FUO caused by multiple myeloma. METHODS: We reviewed the clinical features of 9 patients seen at Mayo Clinic from January 1, 1975, to February 1, 2001, with FUO caused by multiple myeloma. RESULTS: Fever of unknown origin caused by multiple myeloma was found in 9 patients (6 men and 3 women). All patients satisfied accepted criteria for FUO. The mean +/- SD time from the onset of fevers to the initial physician evaluation was 4.8 +/- 2.0 weeks. The mean time from the initial physician evaluation to the diagnosis of multiple myeloma was 11.4 +/- 6.5 weeks. The mean age at diagnosis of multiple myeloma was 55.9 +/- 6.9 years. All 9 patients were anemic. Peripheral blood smears were available for 8 patients, and all had rouleaux formations. All 9 patients underwent exhaustive testing to determine the cause of fevers. Further testing was done in 6 patients subsequent to the diagnosis of multiple myeloma. Acetaminophen or nonsteroidal anti-inflammatory drugs or both relieved fevers in all patients who received them. All 8 patients who received chemotherapy experienced resolution of fevers. The median actuarial survival of the patient cohort was 38 months. CONCLUSIONS: Multiple myeloma can cause FUO. When appropriate, clinicians should include multiple myeloma in the differential diagnosis of FUO to reduce unnecessary testing, rapidly establish the diagnosis, and initiate effective treatments.     

Fever of unknown origin: large vessel vasculitis diagnosed by PET/CT

PET/CT is starting to play an important role in evaluating fever of unknown origin (FUO), due to its ability to localize and delineate areas of high metabolic activity, such as neoplastic proliferation and inflammation, including vasculitis. We present a case of giant cell arteritis (GCA) in a 72-year-old female patient admitted to our department with a 4-month history of FUO, weight loss and fatigue, without specific symptoms or signs. Laboratory investigations suggested acute phase response, with a pronounced erythrocyte sedimentation rate, high CRP level and microcytic anemia. A thorough diagnostic evaluation was performed to exclude an unknown primary tumor, which was initially suspected due to a positive family history of cancer. Surprisingly, PET/CT revealed large vessel vasculitis affecting the ascending, descending and abdominal aorta, as well as subclavian, proximal brachial and carotid arteries bilaterally. Biopsy of the superficial temporal artery confirmed the diagnosis of GCA. Treatment with methylprednisolone and azathioprine led to resolution of clinical symptoms and normalization of laboratory parameters. In addition to the use of PET/CT in the evaluation of FUO, its value as a method complementary to temporal artery biopsy is also discussed.     

Multiple myeloma presenting as fever of unknown origin

BACKGROUND: Multiple myeloma (MM) itself is not considered to be responsible for fever and is not usually listed among the causes of fever of unknown origin (FUO). METHODS: We report three cases of MM presenting with specific fever that we analyze in combination with the three previously published cases. RESULTS: MM could easily be suspected in most, but not all, cases, emphasizing that bone marrow aspiration should be a part of 'standard' FUO investigations. All patients underwent extensive, sometimes potentially harmful, investigations. Conventional treatment of MM produced a sustained improvement in the temperature curve and inflammatory syndrome in all cases within a few months. Fever recurred during nearly all relapses. Six patients died, one after a disease course of more than 8 years. CONCLUSIONS: This series shows that MM may present as a FUO and that useless and hazardous investigations may be avoided given the possibility of specific fever in this disease. Chemotherapy must be considered without much delay after a reasonable work-up to eliminate any associated process, especially infections.     

Fieber ungeklärter Ursache

Fever of unknown origin (FUO) is defined as sustained unexplained fever despite intensive diagnostic evaluation and represents a particular diagnostic challenge. It can be classified into different categories, e.g. classical, nosocomial, neutropenic and HIV-associated FUO, which is based on the patient-specific clinical and immunological situation. Infections, malignant diseases and non-infectious inflammatory diseases have to be considered as the most important causes of FUO; however, no definitive diagnosis can be established in a substantial number of FUO patients despite an extensive diagnostic work-up. The present review focuses on the important diagnostic aspects as well as therapeutic options in FUO patients.     

Treatment of primary defective iron-reutilization syndrome: revisited

 We encountered two patients who presented with hypochromic–microcytic anemia and were refractory to iron therapy. The symptoms were suggestive of anemia of chronic disease (ACD); however, there was no evidence of any such disease, either inflammatory or malignant. These patients were reminiscent of patients originally described as having primary defective iron reutilization. The hematologic picture consisted of hypochromic–microcytic anemia, low serum iron, low to normal iron binding capacity, high serum ferritin, and increased bone marrow iron in the absence of ringed sideroblasts. These patients had symptomatic anemia and received danazol (200 mg orally) three times per day to which they responded very well with an increase of approximately 3 g in the hemoglobin concentration over 1 year and amelioration of their symptoms. Danazol was well tolerated and did not cause any virilizing side effects. Doses were lowered in maintenance after 1 year to 200 mg once per week, and responses were sustained up to 36 months of follow-up duration. In the differential diagnosis of hypochromic–microcytic anemia, especially in postmenopausal women, one has to consider this type of treatable anemia when more common types such as iron deficiency, chronic inflammation, malignancy, sideroblastic anemia, or thalassemia have been ruled out. Received: 16 June 1999 / Accepted: 1 February 2000     

Takayasu's arteritis presenting as fever of unknown origin: report of two cases and literature review

OBJECTIVES: This study reports two patients with Takayasu's arteritis presenting with a fever of unknown origin (FUO) and reviews the literature on that association. METHODS: We describe the clinical presentation, course, and outcome of the two patients, and reviewed the medical literature from 1968 till 1997 using MEDLINE and the key words fever, diagnosis, and Takayasu's arteritis. RESULTS: Takayasu's arteritis is rarely reported as a cause of FUO. Noninvasive diagnostic techniques such as magnetic resonance imaging, computed tomography scanning, gallium-67 scintigraphy, and ultrasonography may help in the diagnosis of Takayasu's arteritis in the prepulseless stage. CONCLUSION: Takayasu's arteritis should be considered in the differential diagnosis of FUO, especially in young women.     

High prevalence of atrophic body gastritis in patients with unexplained microcytic and macrocytic anemia: a prospective screening study

OBJECTIVE: Atrophic body gastritis (ABG) is characterized by atrophy of the gastric body mucosa, hypergastrinemia, and hypo/achlorhydria. Its association with pernicious anemia is well recognized. Gastric hypo/achlorhydria is known to affect iron absorption but ABG is rarely considered as a possible cause of iron deficiency (microcytic) anemia. The aims of this study were to validate a screening methodology for the detection of ABG in a consecutive series of patients with microcytic and macrocytic anemia and to investigate the clinical and gastric morphofunctional characteristics of the two hematological presentations of ABG. METHODS: A two-part prospective study was carried out. Part A aimed to validate the screening methodology to detect the presence of ABG in patients with macrocytic and microcytic anemia who have no specific GI symptoms, by measuring their gastrin levels and verified by performing gastroscopy with biopsy. Part B aimed to detect the presence of ABG in a larger sample of anemic patients by our validated method and, by pooling the data of ABG patients, to determine the clinical, gastric histological, and functional characteristics pertaining to the macrocytic and microcytic presentations of ABG. RESULTS: In part A, ABG was detected in 37.5% of patients with macrocytic and in 19.5% of those with microcytic anemia. Pooling the data of the ABG patients from part A and part B, microcytic ABG patients were on average 20 yr younger than those with macrocytic anemia. The majority of microcytic ABG patients were female, most of whom were premenopausal. H. pylori infection was widely represented in the microcytic ABG group (61.1%). They also had a lesser grade of body mucosal atrophy and lower hypergastrinemia levels, suggesting a less severe oxyntic damage of shorter duration. CONCLUSIONS: Macrocytic anemia is not the only hematological presentation of ABG. Physicians evaluating patients with unexplained iron deficiency anemia should consider ABG as a possible cause by determining fasting gastrin levels and performing gastroscopy with biopsies of the body mucosa.     

PET-imaging proves giant-cell arteritis as the cause of FUO in a patient with a pulmonary nodule of unknown malignancy

Positron emission tomography (PET) has emerged as a powerful tool in clinical oncology which allows to detect pathological changes in the metabolic characteristics of different tissues. In recent years the PET with the radiopharmakon 18F-2-fluoro-2-deoxyglucose has proved to be valuable for the diagnostic approach in inflammatory diseases. We report the case of a 69 year old female patient who was admitted for the diagnostic evaluation of a single pulmonary nodule in the right upper lobe which was suspicious for malignancy in the CT scanning. In the last three month the patient lost 13 kg weight, and was complaining about weakness, fatigue, enhanced body temperature up to 101 degrees F and night sweets. In the laboratory findings a microcytic anemia (80 g/L, 74,4 fL), an enhanced C-reactive protein (133 mg/L) and an accelerated ESR of 100 mm Hg/h was remarkable. The pulmonary nodule located in the second segment of the right upper lobe was not accessible in the bronchoscopic examination. Abdominal and cerebral CT scannings showed no pathological findings. In the positron emission tomography an enhanced accumulation of 18F-2-fluoro-2-deoxyglucose could be detected in the complete aorta and the large-sized arteries of the aortic arch consistent with the diagnosis of a giant-cell arteritis. The suspicious pulmonary nodule of the CT scanning showed no metabolic activity as provable with the PET. The 18F-FDG PET which is used in the initial staging of newly diagnosed lung cancer and known to be superior to CT in the evaluation of lymph node and distant metastases, is applicable in the diagnostic assessment of chronic inflammatory diseases. As the diagnostic approach in patients presenting with clinical symptoms as fatigue, weight loss, night sweets and fever is often arduous and time-consuming, the PET might become a more central role in the future.     

综合医院以不明原因发热为表现的结核病100例临床分析

目的 探讨以不明原因发热(FUO)为表现的结核病的临床特征.方法 回顾性分析100例北京协和医院确诊的以FUO为表现的结核病患者的临床资料.结果 (1)结核累及部位:单纯肺结核39例,单纯肺外结核28例,肺结核合并肺外结核33例.(2)临床表现:由于累及部位的不同,伴随症状各异.实验室检查多为ESR增快和C反应蛋白升高以及不同程度的消耗表现即贫血和低白蛋白血症.(3)诊断方法:抗酸杆菌阳性的34例,组织病理符合结核病的8例,临床诊断并经抗结核治疗有效的49例,诊断性抗结核治疗有效的9例.从发病至确诊的时间为3～77周,中位确诊时间14周.(4)治疗反应:73例随访的患者中仅有2例(2.7%)死亡,其余均好转或治愈.正规抗结核治疗4周以内显效率为77.5%.37例(52.1%)出现药物不良反应,经调整治疗方案和对症处理后均好转.结论 以FUO为表现的结核病诊断比较困难,应对该病临床表现进行综合分析,认真阅读胸部影像学资料,尽可能寻找病原学和病理学的证据,必要时可给予诊断性抗结核治疗.     

Ischemic colitis of the cecum after renal transplantation masquerading as malignant disease

Fourteen years after kidney transplantation and following protracted rejection of the transplant, a patient developed abdominal pain, fever, and leukocytosis. Ultrasound demonstrated a pericolic abscess, and barium enema a deformity of the ascending colon suggesting malignant growth. Colonoscopy showed ulcerative and necrotic lesions of the cecum, and colonic carcinoma was suspected. At surgery, a granulomatous inflammatory reaction with fibrosis involving the kidney transplant and cecum was found. Histological examination revealed ulcerations secondary to ischemic colitis, but no malignancy. Thus, ischemic colitis should be ruled out in cases with a presumptive diagnosis of colonic malignancy at x-ray or endoscopy.     

Fever of unknown origin: chronic lymphatic leukemia versus lymphoma (Richter's transformation)

Currently, malignancies are more common than infections as a cause of fever of unknown origin (FUO) in adults. Many malignant disorders are associated with fever, which may either be of the hectic-septic variety resembling an infectious disease or prolonged and low-grade. Neoplasms with either kind of fever may present as an FUO. The malignancies usually associated with fever are lymphoreticular malignancies involving the blood, liver, spleen, or bone marrow. Most malignancies do not have fever, e.g., chronic lymphatic leukemia (CLL), as part of their clinical presentation. We present a case of long-standing CLL in an elderly woman who presented with an FUO. Initially, it was thought that her FUO was caused by CLL or a CLL-related opportunistic infection. The naprosyn test was used in this patient with CLL and FUO to differentiate a malignant from an infectious etiology. Her response to naprosyn indicated that the etiology of her FUO was neoplastic rather than infectious. The absence of tonsillar enlargement and peripheral adenopathy, as well as the presence of fever, argued against CLL as the cause of her fever. Computed axial tomography scans showed central adenopathy in addition to splenomegaly. The presence of fever, splenomegaly, and central adenopathy indicated that the cause of her FUO was a lymphoma (Richter's transformation) and not CLL.     

An uncommon cause of fever in the elderly: late-onset systemic lupus erythematosus

Infections, tumors and multisystem disease are common causes of fever of unknown origin (FUO) in the elderly. Late-onset systemic lupus erythematosus (LO-SLE) is a very rare cause of FUO in elderly patients. Serositis and musculoskeletal manifestations are common, but fever as an initial manifestation in LO-SLE is rare. We present two patients with LO-SLE who manifested fever as an initial symptom. Fever was the only symptom for 2 months in the first case and for 3 months in the second. In conclusion, in geriatric patients who have fever, LO-SLE should be considered in the differential diagnosis.Abbreviations ANA Antinuclear antibody - ESR Erythrocyte sedimentation rate - HBV Hepatitis B - HCV Hepatitis C - CMV Cytomegalovirus - FUO Fever of unknown origin - HIV Human immunodeficiency virus - LO-SLE Late-onset systemic lupus erythematosus - RF Rheumatoid factor     

Fever of unknown origin: temporal arteritis presenting with persistent cough and elevated serum ferritin levels

BACKGROUND: Fever of unknown origin (FUO) at the present time is most frequently caused by neoplasm and less commonly by infection. Currently, collagen vascular diseases (CVDs) are an uncommon cause of FUO because most are readily diagnosable by serologic methods and do not remain undiagnosed for sufficient time to present as FUOs. CVDs presenting as FUOs not readily diagnosable with specific tests include late-onset rheumatoid arthritis, adult juvenile rheumatoid arthritis, and polymyalgia rheumatica/temporal arteritis (TA). TA, or giant cell arteritis, is an uncommon arteritis of the mid- and large-sized extracranial arteries of the head and neck and is a rare cause of FUO. TA is characterized by headache, scalp tenderness, jaw pain on chewing, and sudden loss of vision. Fever, anorexia, weight loss, and night sweats may also be present. With TA, respiratory symptoms occur in 9% and are the presenting feature in 4%. Laboratory abnormalities associated with TA include a highly elevated erythrocyte sedimentation rate, anemia, and thrombocytosis, and mildly increased alkaline phosphatase/serum transaminases. PATIENT: We present a patient with FUO caused by TA whose predominant presenting symptom was persistent cough that overshadowed head and neck symptoms of TA. To the best of our knowledge, this is the first case of TA presenting as an FUO, with a highly elevated serum ferritin level. RESULTS: We conclude that highly elevated serum ferritin levels in patients with FUO should alert the clinician to consider TA in the differential diagnosis.     

Three cases of fever of unknown origin (FUO) with acute multifocal non-bacterial osteitis (NBO) as reactive osteomyelitis

Evaluation for fever of unknown origin (FUO) requires a long list of studies. Recently, the validity of PET scan in FUO evaluation has been approved for screening and qualification. Non-bacterial osteitis (NBO) refers to non-bacterial and non-specific inflammation of bone, which is usually chronic, and involves multiple bony sites. We have experienced 3 cases of FUO associated with increased symmetric multiple fluorodeoxyglucose uptake preferentially at the epiphysis of the femur and tibia on fusion Positron emission tomography/Computed tomography (PET/CT). Patients were young women, who complained of intermittent fever lasting several months, which was associated only with neutropenia and relative lymphocytosis. Bone biopsies revealed increased lymphocytes and histiocyte infiltration of the cortical bone with reactive bone marrow. With no evidence of infection, the fever showed spontaneous remission within 2 weeks of conservative treatment. We report on 3 cases of FUO with self-limited acute NBO as reactive osteomyelitis and suggest that this unique pattern on PET/CT would be helpful for FUO evaluation.     

Fever of unknown origin: an evidence-based review

ABSTRACT:: Fever is a common problem for which patients seek medical advice. Fortunately, in most cases, fever is self-limiting or the etiology of fever is promptly established. Sustained, unexplained fever despite a comprehensive work up is recognized as fever of unknown origin (FUO), which frequently poses a clinical challenge. For a methodical approach, FUO is recently categorized into classic FUO, nosocomial FUO, neutropenic FUO and HIV-associated FUO based on the clinical setting and patient's underlying immune status. This review focuses on the key factors of classic FUO. The etiologic clues obtainable from the history, bedside physical examination findings and pertinent laboratory tests are discussed. Also, FUO in older patients and tuberculosis as a cause of FUO are briefly discussed.     

Giant cell arteritis and secondary amyloidosis: the natural history

Giant cell (temporal) arteritis (GCA) may be a cause of fever of unknown origin (FUO) in elderly patients. The development of secondary (reactive) amyloidosis is an unusual complication of the disease. We describe a 65-year-old male patient who was hospitalized in our hospital with FUO and was diagnosed as having GCA 5 years later. At that time, he also had a nephrotic syndrome and secondary amyloidosis (AA-type). He died due to end-stage renal failure. The probable explanation for the development of this rare complication might be the late diagnosis of this chronic inflammatory disease, which was left untreated for a long period of time.