FUU is currently classified into four different categories:

FUU is body temperature of ? 38.3 ° C (101 ° F) rectally, which is not caused by temporary and selbstlimiterte disease or rapidly fatal disease or diseases associated with unique localized symptoms or signs or with irregularities to common investigations such as X-ray, urine analysis accompanied, or blood cultures. FUU is currently classified into four different categories: Classic FUU: Fieberr for> 3 wks. without apparent cause after 3 days hospital evaluation or ? 3 outpatient visits FUU in medical care: fever in hospitalized patients with acute care without present infection or incubation at recording when the diagnosis remains uncertain after 3 days with appropriate evaluation. Immunodeficient FUU: fever in patients with immunodeficiency, remains if the diagnosis after 3 days of appropriate evaluation, including negative cultures after 48 h uncertain. HIV-related FUU: fever for> 3 weeks in outpatients with confirmed HIV infection or> 3 days in hospitalized patients with confirmed HIV infection if the diagnosis after appropriate evaluation remains uncertain. Etiology causes of FUU are usually divided into four categories (see table: Some causes of FUU): infections (25-50%) and connective tissue disorders (10-20%) neoplasms (5-35%) Other (15- 25%) infections are the most common cause of FUU. In patients with HIV infection, should by opportunistic infections (eg TB;. Infection by atypical mycobacteria, fungi or cytomegalovirus spreads) are sought. Common diseases of the connective tissue close SLE, RA, giant cell arteritis, vasculitis, and juvenile RA in adults (adult Still’s disease) tools. The most common causes are Neoplastic lymphoma, leukemia, renal cell carcinoma, gastrointestinal tumors and metastatic ovarian cancer. However, the occurrence of neoplastic causes has been declining for fever of unknown origin, probably because they are detected by sonography and CT, which are now widely used during the first evaluation. Important causes are different drug effects, deep vein thrombosis, recurrent pulmonary embolism, sarcoidosis, inflammatory bowel disease and artificial fever. In about 10% of adults there is no cause for FUU. Some causes of FUU Cause Suggestive Findings Diagnostic Approach * Contagious abscesses (abdominal, pelvic, dental) abdominal or pelvic discomfort, mostly sensitivity Sometimes zurückliegenede surgery, trauma, diverticulosis, peritonitis or gynecological procedure CT or MRI cat scratch disease recently by a scratched or licked cat Regional adenopathy Parinaud oculoglandular syndrome, headaches Culture (sometimes aspirate of lymph nodes), similar antibody titers, PCR tests CMV infection Recent blood transfusion from CMV-positive donor syndromes mononucleosis (fatigue, easy hepatitis, splenomegaly, lymphadenopathy) Chorioretinitis CMV IgM antibody titers may PCR tests EBV infection sore throat, lymphadenopathy, right upper quadrant tenderness, splenomegaly, fatigue Usually occurring in adolescents and young adults in the elderly, typical findings may not be present Serological tests HIV infection Back Lying high-risk behavior (eg. As unprotected sex, sharing needles) weight loss, night sweats, fatigue, swollen lymph nodes, opportunistic infections tests for HIV antibodies (ie, ELISA, Western blot) Sometimes tests for HIV RNA (for acute HIV infection) infectious endocarditis often past risk factors (z. B. structural heart disease, artificial heart valve, periodontitis, IV catheters, drug use) Normally, a heart murmur, sometimes extracardiac manifestations (eg. B. splitter bleeding, petechiae, Roth spots, Osler node, Janeway lesions, joint pain or effusion , splenomegaly) Serial blood cultures, echocardiography disease Visiting or living in an endemic area erythema migrans rash, headache, fatigue, Bell palsy, meningitis, radiculopathy, heart block, joint pain and swelling Serological tests osteomyelitis Localisable pain, swelling, redness X-rays Sometimes MRI (accurate test), scintigraphy with indium 111-, bone scan sinusitis Prolonged congestion, headaches, facial pain CT sinus TB (pulmonary and disseminated) In the Past exposed to high risk cough, weight loss, fatigue use of immunosuppressants Past HIV infection chest x-ray, PPD, interferon-gamma release assays sputum smear for acid-fast bacilli, nucleic acid amplification tests (NAAT), culture of body fluids (eg. B. stomach sucked, sputum, cerebrospinal fluid) Rare infections (eg, brucellosis, malaria, Q fever, toxoplasmosis, trichinosis, typhoid) Past r travel to endemic areas Exposure to or ingestion of certain animal products Serological tests for individual causes Peripheral blood smears for malaria connective tissue Adult Still’s disease Temporary salmon pink rash, joint pain, arthritis, myalgia, cervical lymphadenopathy, sore throat, cough, chest pain ANA, RF, serum ferritin concentration, Röntg enaufnahmen the affected joints giant cell (temporal) Unilateral headache, blurred vision often symptoms of polymyalgia rheumatica, sometimes jaw claudication sensitivity of the temporal artery in scanning ESR, temporal artery biopsy polyarteritis nodosa fever, weight loss, muscle pain, joint pain, purpura, hematuria, abdominal pain, testicular pain, angina, livedo reticularis, new-onset hypertension biopsy of the involved tissue or angiography polymyalgia rheumatica In the past Morgenstei stiffness in the shoulders, hips and neck discomfort, fatigue, loss of appetite may synovitis, bursitis, edema of extremities creatinine kinase, ANA, RF, ESR may MRI of the extremities reactive arthritis Sometimes recent infection with Chlamydia, Salmonella, Yersinia, Campylobacter, or Shigella Asymmetric oligoarthritis, urethritis, conjunctivitis, genital ulcerations ANA, RF, serological tests for causative pathogens Rheumatoid arthritis: Symmetrical peripheral arthritis, prolonged morning stiffness, subcutaneous rheumatoid nodules at pressure points (extensor surfaces of the ulna, sacrum, mind Oh illes tendon) ANA, RF, citrulline peptide antibody (anti-CCP), X-rays (to identify identify bone erosions) SLE fatigue, joint pain, pleuristische pain, erythemal skin rash, tender swollen joints, mild peripheral edema, Raynaud’s syndrome, serositis, nephritis , alopecia Clinical criteria, ANA, antibodies to double-stranded DNA Neoplastic colon abdominal pain, change in bowel habits, hematochezia, weakness, nausea, vomiting, weight loss, fatigue Colonoscopy, biopsy hepatoma Past chronic liver disease, abdominal pain, weight loss, early satiety, palpable mass in the right upper quadrant abdominal ultrasonography and CT, liver biopsy leukemia Sometimes past myelodysplastic disorder fatigue, weight loss, bleeding, pallor, petechiae, ecchymosis, anorexia, splenomegaly, bone pain CBC, bone marrow examination lymphoma Painless adenopathy, weight loss, fatigue, night sweats, splenomegaly, Hepatomega lie lymph node biopsy metastatic cancer symptoms dependent (from the site of metastasis for. As cough and shortness of breath for lung metastases, headache and dizziness for brain metastasis) often asymptomatic, during a routine medical examination discovered biopsy of the suspect mass or nodes imaging method according to the areas concerned Myeloproliferative diseases often asymptomatic, first detected abnormal occurrence in the CBC Screening tests are based on the presumed impairment renal cell carcinoma weight loss, night sweats, flank pain, hematuria, palpable flank mass, hypertension serum calcium of (for the detection of hypercalcemia), urinalysis, CT Kidney Other Alcoholic cirrhosis long history of alcohol use Sometimes ascites, jaundice, small or enlarged liver, gynecomastia, Dupuytren- contractures, testicular atrophy PT / PTT, alkaline phosphatase, transaminases, albumin, bilirubin Sometimes abdominal sonography and CT Deep vein thrombosis pain, swelling sometimes redness of the leg ultrasonography D-dimer assay drug fever falls sometimes together with the administration of a drug (usually within 7-10 days) Sometimes a rash drug discontinuation Artificial fever dramatic, atypical appearance, vague and inconsistent details, knowledge of textbook descriptions, compulsive or habitual lies (Pseudologia Fantastica) diagnosis of exclusion. Inflammatory bowel disease abdominal pain, diarrhea (sometimes bloody), weight loss, guajakpositiven stools Sometimes fistulas, perianal and oral ulcers, arthralgias endoscopy of the upper digestive system with small bowel barium enema or CT Enterographie (Crohn’s disease) colonoscopy (ulcerative colitis or Crohn’s colitis) * missing in patients with FUU possibly typical findings, but after this should be sought. ANA = antibodies to cell nuclei; ANCA = antineutrophil cytoplasmic antibody; CMV = cytomegalovirus; EBV = Epstein-Barr virus, ELISA = enzyme-linked immunosorbent assay; RF = rheumatoid factor. In evaluating puzzling cases as FUU, it is to presuppose a mistake that all information collected or exactly collected by previous doctors. Doctors should pay attention to what the patient already reported (to fix discrepancies), but he should not simply details of the previously recorded Copy reports. (Z. B. family history, social history). Initial omission errors have been maintained by many doctors for a long day of hospital stay, which a lot of unnecessary tests result had. Even if the first evaluation was thorough, to remind patients often renewed interrogations of new details. Conversely, physicians should not ignore previous test results and should not repeat tests without paying attention to how likely it is to obtain different results. (Z. B. because the patient’s condition has changed, because a disease develops slowly). History The medical history should focal symptoms are revealed and factors (eg. As travel, work, family history, exposure to animal vectors dietary past), which might be a cause. In the history of the present illness duration and pattern (constant z. B. interruptions) should be determined by fever. Fever pattern usually have little or no diagnostic value in FUU although fever every other day (tertian fever) or every 3 days (fever quartan) occurs may be an indication of malaria in patients with risk factors. Focal pain often provide the location (though not the cause) of the underlying disease. Doctors should first generally, then ask en especially after complaints in each body part. The examination of the body systems should include non-specific symptoms such as weight loss, loss of appetite, fatigue, night sweats and headaches. Furthermore (diarrhea, steatorrhea, abdominal pain z. B.) should be looked for symptoms of connective tissue diseases (eg. As muscle pain, joint pain, skin rashes), and gastrointestinal disorders. History should cause diseases that are known fever, such as cancer, tuberculosis, connective tissue disorders, alcoholic cirrhosis, inflammatory bowel disease, rheumatic fever and include hyperthyroidism. Doctors should Disorders or factors that promote infection such as immune deficiency ((z. B. from diseases such as HIV infection, cancer, diabetes, or the use of immunosuppressive drugs), structural heart disease, urinary tract abnormalities, surgery and insertion of devices such note intravenous access, cardiac pacemakers, prosthetic joints). B.. The medical history to medicines also questions about specific drugs should be made available cause fever. Questions about the social background should provide information on infectious risk factors such. As the consumption of injected drugs, risky sexual practices (eg. As unprotected sex, different partners) contact with infected people (eg. As with TB), traveling, and possible exposure to animals or insects as vectors. Risk factors for cancer, such as smoking, alcohol consumption, and exposure to chemicals should also be recognized. Family history should include questions about inherited causes of fever (z. B. Familial Mediterranean fever). Medical reports are examined on earlier test results indicate, especially those with certain diseases exclude lassen.Körperliche investigation The general appearance, especially cachexia, jaundice and pallor, is noted. The skin is thoroughly focal erythema (which may indicate a focus of infection) is checked, and rash (e.g., malar rash in SLE.) Out; the study should include the perineum and the feet, especially in diabetics who are prone to infections in these areas. Doctors should check lesions by endocarditis what painful subcutaneous microembolisms at the fingertips (Osler’s Node), painless hemorrhagic lesions including on the palms or soles (Janeway lesions) and splinter hemorrhages under the nails. The entire body (especially the spine, bones, joints, stomach and thyroid) should be scanned for tenderness, swelling or organomegaly; digital rectal examination and gynecological examination belong to the teeth on sensitivity towards taps (refers to an apical abscess). During palpation any regional or systemic adenopathy is noted for. B. Regional adenopathy t characteristic of cat scratch disease in contrast to diffuse lymphadenopathy. The heart is to noises (suggesting a bacterial endocarditis) and friction (resulting in a, pericarditis suggesting due to rhematologischen or infectious disease) tapped. Sometimes or seem important physical abnormalities in patients with FUU so subtle that repeated physical examinations are necessary to the causes (eg., By detecting new adenopathy, heart murmurs, rash, or nodules and weak pulsations in the temporal artery) herauszufinden.Warnhinweise The following are particularly important: immunodeficiency murmurs Implanted devices (eg intravenous access pacemakers, prosthetic joints.) Kur past travel to endemic areas interpretation of results After a thorough history and physical examination, the following scenarios are typical: Local symptoms or signs that do not occurred, not detected, or when previous studies have not been found to be detected. These results are interpreted and analyzed as indicated (see table: Some causes of FUU). only nonspecific findings are often in the evaluation recognized that occur in many different causes of FUU, but it used to determine the risk factors that can help in the implementation of tests (eg. as travel to endemic areas, exposure to animal vectors) , Sometimes risk factors are less specific and point only to a group of diseases out for. As weight loss without anorexia is more related to infections as a cancer that causes usually anorexia. Possible causes should be investigated further. In the most difficult cases, patients have nonspecific findings and zero or more risk factors, so logical, sequential approaches to Diagnostikvon are essential. Initial tests are designed to narrow the diagnostic possibilities and to be a benchmark for subsequent testing. Tests Preceding test results, especially from cultures must be checked. In some organisms, it takes time until the cultures show a positive result. As much as possible clinical information is used to manifest the tests. (See table: Some causes of FUU). For example bound to the house, older patients would be tested with a headache is not a tick-borne infections or malaria, but these diseases should be considered in younger travelers who have migrated in an endemic area into consideration. Elderly patients need to be reviewed for giant cell arteritis; younger patients do not. In addition to specific tests, the following should be done: CBC with differential ESR liver Serial blood cultures (ideally before antimicrobial therapy) HIV antibody test, RNA concentration evidence and PCR evidence tuberculin skin test or interferon-gamma release evidence Although earlier performed these tests can help indicate a rich trend. Urinalysis, urine culture and radiograph of the chest cavity that have already been carried out as a rule will only be repeated if appropriate findings can deem necessary. All available liquids or materials of abnormal areas that have been identified during the evaluation are cultivated. (Eg., Bacteria, mycobacteria, fungi, viruses or certain fastidious bacteria as indicated). Organismuspezifische tests such as PCR and serological titer (acute and convalescent) are mainly useful when they are guided by clinical suspicion, and not in the snapshot process. Serological tests such as antinuclear antibodies (ANA) and rheumatoid factor are performed to look for rheumatic diseases. Imaging methods are determined by the symptoms and signs. Normally, the areas should cause discomfort, displayed -z. (To check infections or tumors) as in patients with back pain, MRI of the spinal column; in patients with abdominal pain, CT of the abdomen. However, a CT of the thorax, abdomen and pelvis should be considered to test for adenopathy and occult abscesses back, even if patients are not local symptoms or signs. With positive blood cultures, or heart murmurs or peripheral symptoms suggestive of endocarditis, an echocardiogram is performed. In general, a CT is useful to delineate anomalies in the stomach or chest area. MRI is more sensitive than CT in the evaluation of a cause FUU with cerebral involvement and should always be durchgeführ when a cerebral cause is considered. Venous duplex imaging may be useful in cases of deep vein thrombosis. Scintigraphy with indium-111-labeled granulocytes can help to locate some infectious or inflammatory processes. This technique is generally out of favor because it is believed that it contributes very little to the diagnosis, but some reports suggest that it has a higher diagnostic hit rate than CT. PET may also be useful in the detection of fever cooker A biopsy is required when an abnormality is suspected in the tissue, which is accessible for a biopsy (eg., Liver, bone marrow, skin, pleura, lymph nodes, intestine or muscle). Biopsy samples should be histopathologically and culturally tested for bacteria, fungi, viruses and mycobacteria or through a PCR detection. Muscle biopsies or skin biopsies of rashes can confirm vasculitis. Bilateral biopsy of the temporal arteries can confirm the diagnosis of Temporalarterienarteriitis in elderly patients with unexplained ESR increase. Therapy Treatment of FUO focuses on the causal disease. Antipyretics should be used with caution, taking into account the duration of fever. Geriatrics Basics: FUO causes of FUU in the elderly are generally similar to those in the general population, but connective tissue diseases are frequently identified. The most common causes are giant cell lymphomas abscesses TB Key Points Classic FUU’s body temperature ? 38.0 ° C rectally for> 3 wks. without apparent cause after 3 days hospital examination or ? 3 outpatient visits. Identified causes can be classified as infectious, connective tissue, neoplastic or different. The evaluation should be based on the synthesis of medical history and physical examination, with special attention to risk factors and possible causes based on individual circumstances.


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