FEBRILE PATIENT Most patients with fever have associated symptoms that make diagnosis strightfoward. The majority have viral respiratory infections or uncomplicated bacterial respiratory or urinary infections. A careful history and a full examination have a great value. If the diagnosis is not immediately obvious, particular attention should be paid to special features of history and examination, listed further under PUO. First line investigations include full blood count, urinalysis and chest X-ray. Antibiotics should never be started until appropriate cultures have been sent. Epidemiological data - recent overseas travel, exposure to human or animal contacts, known outbreak of e.g. influenza, measles, bronchiolitis. Clinical presentation: Infection - acute onset of fever, an obvious focus of inflammation or sepsis or a predisposing cause such as immunosupression. Helpful features associated with fever in infections: Tonsillitis – acute onset with high fever suggests streptococcal disease, more insidious onset inf. mononucleosis. Tuberculosis – fever may resolve with bed rest. Brief, high spikes of fever – bedsores. Fever without associated rise in pulse rate – typhoid fever, brucellosis, factitious fever. Rigors = uncontrollable shivering lasting up to half an hour, followed by profuse sweating, associated with rapid rise of temperature, associated with malaria, lobar pneumonia, cholecystitis, pyelonephritis, sepsis. (Chills = brief episodes of shivering.) Headache is common with fever, usual in influenza, typhoid fever, meningitis, localized headache in sinusitis and mastoiditis. Delirium: confusion, hallucinations and nightmares are seen with fever, esp. in children, in lobar pneumonia and sepsis. Abrupt withdrawal of alcohol due to illness in habituated persons may contribute to confusion and delirium. Meningism in intracranial infection, but esp. in children is frequent in other febrile conditions such as strep. tonsillitis, pneumonia and pyelonephritis. Febrile convulsions in children up to the age of six. Abdominal pain often associated with fever in children, caused by alterations of intestinal motility or tender intraabdominal lymhp nodes. Other causes such as appendicitis must be excluded. Clinical examination - special attention to: - respiratory tract (middle ear in children) incl. paranasal sinuses, lungs - spleen for enlargement - skin and buccal mucosa for rashes - abdomen for tenderness - neck for lymph nodes and stiffness - eyes for photophobia - fontanelle for bulging Laboratory investigations appropriate to clinical symptoms, some providing rapid, some later results. Management, if the cause of fever is not quickly demonstrated: a) Treat symptoms and observe closely – in not very ill pt., who may recover rapidly. b) Keep the pt. under constant review while further results of investigations are awaited – in moderately ill pt. Antimicrobial therapy may mask an important diagnosis. c) Start empirical antimicrobial therapy after initial specimens have been taken – in potentially life-threatening circumstances. The choice of antimicrobial therapy is based upon judgement of possible infectious causes. Sometimes the response is taken as confirmatory evidence of diagnosis. PYREXIA OF UNKNOWN ORIGIN (PUO) is a fever which has persisted for at least 7-10 days and is still unexplained after one or more medical consultations. The possible causes of PUO: 1. - Infections (45-55%): tuberculosis – extrapulmonary, miliary sepsis or abscess imported diseases – typhoid fever, brucellosis, amoebic abscess infective endocarditis zoonoses with subacute or chronic course 2. Malignancies (12-20%): - haematological: lymphoma, leukaemia, histiocytosis - visceral: kidney, liver, pancreas 3. Connective tissue disorders, autoimmunity (10-15%): - rheumatological: rheumatoid arthritis, SLE, polyarteritis nodosa, dermatomyositis, temporal arteritis - granulomatous: sarcoidosis, Crohn´s disease, granulomatous hepatitis 4. Hypersensitivity disorders: - drugs: sulphonamides, penicillins, isoniazid, streptomycin, amphotericin B, phenytoin, methyldopa - environmental factors: fungus-infected hay (farmer´s lung), bird proteins (pigeon-fancier´s lung) 5. Rare metabolic disorders: porphyrias, familiar relapsing polyserositis (Mediterranean fever), VIPoma and glucagonoma 6. Factitious fever Temperature – axillar, oral, rectal To exclude or monitor fever, single or occasional readings are inadequate and three-hourly temperature chart is helpful. Fever: A) physiological – variations throughout the day, exposure to extreme weather conditions, clothing, activity, ovulation B) pathological C) factitious – patient manipulate his temperature recordings D) fraudulent – real, but deliberately induced fever Pattern of fever: continuous, constant – meningitis, pneumonia, typhoid fever intermittent - malaria, relapsing fever swinging with periods of remission – tuberculosis, chronic vasculitis, spiking - abscess undulant – brucellosis, Hodgkin´s disease Work-up plan: 1. History: (besides previous medical history and history of present illness) Exposure to infection: contact with other cases, travel, food, water, occupation, recreation, animals - pets, sexual risk contacts Exposure to allergens: drugs, cotton, hay, bird protein, industrial dusts and vapours Predisposition: family history of relapsing serositis, Reiter´s syndrome and connective tissue diseases Exposure to carcinogenic agents Protection or resistance - after previous infection, active or passive immunization, use of chemoprophylaxis 2. Physical examination should be repeated at daily intervals in patients in hospital, looking particularly for: heart murmurs chest signs lymph nodes localized bone or joint pain – discomfort, stifness, in children reluctance to move skin rashes, nail for splinters mild meningism mild localized abdominal tenderness 3. Routine investigations (before the label of PUO is applied, repeat them, particularly if they were performed early in the course of illness): - blood count, differential WBC count - ESR, CRP - blood culture - urine – biochemistry, microscopy of sediment, culture - sputum microscopy, culture - CSF, stool, aspirates culture, if indicated - biochemical screen – renal and liver tests, electrolytes, thyroid tests - chest X-ray In patients at risk for tuberculosis or if suspected for any reason: - sputum and early morning urine for acid-fast bacilli and tuberculosis culture on three ocassions (+ PCR) - CSF for AFBs if indicated(+PCR) - tuberculin test 4. Second-line investigations (depending on clinical picture): Tests for connective tissue and granulomatous disease: rheumatoid factor, anti-nuclear antibodies, double-stranded-DNA antibodies, organ-specific antibodies (smooth-muscle, mitochondria, thyroid), anti-neutrophil cytoplasmic antibodies (ANCA), complement levels, immunoglobulins Serology (depending on suspected agent): viral – flu, adenovirus, herpes, mumps, measles, parvovirus, HIV bacterial – mycoplasma, chlamydia, syphilis, leptospirosis, legionella, brucella Imaging: ultrasonography – upper abdomen, pelvis echocardiography computed tomography (+ guided aspiration if indicated) magnetic resonance imaging radioisotope scans (bone scan, radiolabelled leukocytes) X-ray techniques laparoscopy, bronchoscopy, GIT endoscopy, cystoscopy, mediastinoscopy Biopsy - liver, lymph node, bone marrow, skin lesion, temporal artery Therapeutic trial after all possible specimens were obtained: Reasons: 1. To gain further evidence for a suspected diagnosis - expected response (suspected specific infection – give drug with the narrowest possible spectrum). 2. A "blind" trial, when the patient´s condition is critical. Risks: Antibiotics: reduced usefulness of diagnostic cultures modification of infection without cure adverse side-effects complicating the illness Corticosteroids: reduced usefulness of immunological tests progression of the infection with reduced signs of inflammation In about 5 % no diagnosis was done and no improvement is obtained. About half of these cases eventually recover and most of the others remain feverish but do not deteriorate.