ETIOLOGY & PATHOPHYSIOLOGY OF PYREXIA OF UNKNOWN ORIGIN (PUO) &

PNEUMONIA

PYREXIA OF UNKNOWN ORIGIN (PUO)

Defi niti on

Petersdorf and Beeson defined pyrexia of unknown origin (PUO) in 1961. It is defined as:

A temperature greater than 38.3°C on several occasions. This should be accompanied by more than 3 weeks of

illness. There should also be failure to reach a diagnosis, after 1

week of inpatient investigation.

Pathophysiology • Fever is a natural response of the body that helps in fighting

off foreign substances, such as microorganisms, toxins, etc.• Body temperature is set by the thermoregulatory center,

located in an area in the brain called hypothalamus. cytokines cause the thermoregulatory center in the hypothalamus to reset the normal temperature level.

• The body's initial response is to conserve heat by vasoconstriction, a process in which blood vessels narrow and prevent heat loss from the skin and elsewhere. This alone will raise temperature by two to three degrees.

• Fever is a body defense mechanism. It has been shown that one of the effects of temperature increase is to slow bacterial growth.

Common causes of PUO Most cases are unusual presentations of

common diseases e.g. tuberculosis, endocarditis, gallbladder disease and HIV infection, rather than rare or exotic diseases.

• In adults: infections and cancer (25-40% of cases each) account for most of PUOs.

• Children: 30-50% of cases are due to infections, 5-10% cancer, autoimmune disorders 10-20%.

Bacterial

• Abscesses – There may be no localising symptoms. – Previous abdominal or pelvic surgery, trauma .– Most commonly in the subphrenic space, liver,

right lower quadrant, retroperitoneal space or the pelvis in women.

• Tuberculosis (TB) – caused by Mycobacterium tuberculosis in humans.

Most infections in humans result in an asymptomatic.– The classic symptoms are a chronic cough with blood-

tinged sputum, fever, night sweats, and weight loss. Infection of other organs .

– More people in the developed world are contracting tuberculosis because their immune systems are compromised by immunosuppressive drugs, substance abuse, or AIDS.

• Urinary tract infections (UTIs) are rare causes. Perinephric abscesses occasionally fail to communicate with the urinary system resulting in a normal urinalysis

• Hepatobiliary infections e.g. cholangitis can occur without local signs and with only mildly elevated or normal liver function tests especially in the elderly.

• Osteomyelitis Subacute in onset, there is dull, constant pain and soft tissue swelling/tenderness over the involved bone, with low-grade fever.

• Brucellosis should be considered in patients with persistent fever and a history of contact with cattle, swine, goats or sheep, or patients who consume raw milk products.

• Giant cell arthritis Consider when an elderly patient develops a new headache associated with a tender, ropy, or nodular temporal artery and/or fever.

• Other spirochetal diseases that can cause PUO include Spirillum minor (Rat-bite fever), Borrelia burgdorferi (Lyme disease), and Treponema pallidum (syphilis).

ViralHerpes viruses such as cytomegalovirus and Epstein-Barr virus (EBV) can cause prolonged febrile illnesses with constitutional symptoms and no prominent organ manifestations, particularly in the elderly.

• HIV: – Prolonged febrile episodes are frequent in patients

with advanced HIV infection. – Suspect tuberculosis in high-risk patients such as HIV-

infected persons, tuberculosis is usually extra pulmonary (bones, nodes, renal, genitals, or liver).

– Over 80% of patients with AIDS and lymphomas have involvement of extranodal sites - usually the brain.

Fungi• Immunosuppression, the use of broad-spectrum

antibiotics, the presence of intravascular devices and total parenteral nutrition all predispose people to disseminated fungal infections.

Parasites• Toxoplasmosis: This should be considered in

patients who are febrile with lymph node enlargement.

• Trypanosoma, leishmania and amoeba species may rarely cause PUO.

Rickettsial organismsCoxiella burnetii may cause chronic infections, chronic Q fever or Q fever endocarditis may be identified in patients with a PUO.

Psittacosis• Infection by the causative organism, Chlamydophila

should be considered in a patient with PUO who has a history of contact with birds.

Lymphogranuloma venereum• This should also be considered, but is rare.

Drug fever• The most common are beta-lactam antibiotics,

procainamide (now discontinued) and isoniazid. Stopping the drug generally leads to recovery within 2 days.

• may be due to serum sickness, allergy, or immune-mediated vasculitis.

• It is usually accompanied by a rash.

Collagen vascular and autoimmune diseases• Systemic-onset juvenile rheumatoid arthritis.

High-spiking fevers, non-pruritic rashes, arthralgias and myalgias, pharyngitis and lymphadenopathy typically are present.

• Polyarteritis nodosa (PAN), rheumatoid arthritis and mixed connective-tissue diseases should be considered.

Neoplasms• Hodgkin and non-Hodgkin lymphomas may cause

PUO. • Leukaemias may also be responsible. • Among solid tumours, renal cell carcinoma is most

commonly associated with PUO. Vasculitides• Giant cell arteritis and also the related polymyalgia

rheumatica • Polyarteritis nodosa • Behcet's has also been reported

Inherited diseases• Familial mediterranean fever a hereditary

disease usually seen in Armenians and Sephardic Jews, with short recurrent attacks of fever, pain in the abdomen, chest, or joints, and erythema like that of erysipelas; it may be complicated by amyloidosis.

Hyperthyroidism and subacute thyroiditis• These are the most common endocrine causes of

PUO.

Diagnosis when a fever over 101°F (38.5°C) remains unexplained for

longer than 3 weeks, is usually a result of infection (40%), neoplasm (20%), or collagen-vascular disease (20%).

• Record all complaints even if not currently present.• Discuss nutrition including consumption of products and

source of these products.• Drug history should be recorded, to include over-the-

counter medications, • Immunization status should be documented. • Enquire about family history of illness. • Occupational history should include illicit substances.• Sexual history should be recorded. • Take a history of travel and recreational habits

Examine for subtle clues & Clinical Findings•Extreme elevations of fever (40°C )it is found in heat stroke, hypothalamic dysfunction, meningitis, midbrain hemorrhage,falciparum malaria.• Relative bradycardia occurs typhoid fever, meningitis with increased ICT,factitious fever, tularemia, brucellosis, mumps, hepatitis, and with concomitant beta blockers.

•Relapsing fever (days of fever alternating with days without) occur in brucellosis (fever with physical activity), Hodgkin's disease, extrapulmonary tuberculosis, malaria, and Lyme disease. Hectic fever.• FUO lasts longer than 6 months, consider factitious fever, granulomatous hepatitis, neoplasm, Still disease, infection, collagen-vascular disease.

Jwara samprapti

• Jirna Jwara च. चिच. ३

त्रि�सप्ताहे� व्यता�ता� ता� ज्वरो� यस्तानु�ताम्� गता�। प्लिप्�हे�ग्नि�नुसदम्� कु� रुता� स जी�र्णो%ज्वरोम्�च्यता�।म्.त्रिनु. म्धु�कु�ष

• त्रि�सप्ताहे� Fever continuous after 21 days ,indicating chronicity & long duration of fever may be due to failure in diagnosis or in treatment.

• म्न्दज्वरो : it may be due to failure of immune system to control infections.

• प्लिप्�हेव*द्धी,: Angnimandya lead to disturbance in Dhatupotion Dhatukshaya Vataprakopa Medakshaya Pliharuddhi.

च. चिच. ३

Pneumonia

• Definition Pneumonia is an abnormal inflammatory condition of the

lung. it is often characterized as including inflammation of the parenchyma of the lung (that is, the alveoli) and abnormal alveolar filling with fluid (consolidation and exudation).

• Classification• Early classification schemes

Initial descriptions of pneumonia focused on the anatomic or pathologic appearance of the lung, either by direct inspection at autopsy or by its appearance under a microscope.

• Lobar pneumonia• Interstitial pneumonia• Bronchial pneumonia• Multilobar pneumonia

Combined clinical classificationTraditionally, clinicians have classified pneumonia

by clinical characteristics, dividing them into "acute" (less than three weeks duration) and "chronic" pneumonias.

1. Chronic pneumonias, on the other hand, mainly include those of Nocardia, Actinomyces and Blastomyces as well as the granulomatous pneumonias (Mycobacterium tuberculosis and atypical mycobacteria, Histoplasma capsulatum.

2. Acute pneumonias are further divided into the classic bacterial bronchopneumonia's (such as Streptococcus pneumoniae),The atypical pneumonias (such as the interstitial pneumonitis of Mycoplasma pneumoniae ), and the aspiration pneumonia syndromes.

* There are two broad categories of pneumonia ; 1) Community-acquired pneumonia (CAP) 2)Hospital-acquired pneumonia. A recently introduced type of healthcare-associated pneumonia lies between these two categories.

1) Community-acquired pneumonia (CAP):it is infectious pneumonia in a person who has not recently been hospitalized. CAP is the most common type of pneumonia. Streptococcus pneumoniae is the most common cause of CAP The term "walking pneumonia" has been used to describe a type of community-acquired pneumonia of less severity usually caused by the atypical bacterium, Mycoplasma pneumoniae.

2)Hospital-acquired pneumonia, also called Nosocomial pneumonia, is pneumonia acquired during or after hospitalization for another illness or procedure with onset at least 72 hrs after admission. Hospital-acquired microorganisms may include resistant bacteria such as MRSA, Pseudomonas, Enterobacter, and Serratia. Ventilator-associated pneumonia (VAP) is a subset of HAP, VAP is pneumonia which occurs after at least 48 hours of intubation and mechanical ventilation

Other types of pneumonia

1)Severe acute respiratory syndrome(SARS) .2) Bronchiolitis obliterans organizing pneumonia(BOOP) . 3)Eosinophilic pneumonia. 4)Chemical pneumonia. 5)Aspiration pneumonia. 6)Dust pneumonia.7)Necrotizing pneumonia,

Signs and symptomsPeople with infectious pneumonia often have 1) cough producing greenish or yellow sputum or phlegm. 2)High fever that may be accompanied by shaking chills. 3)Shortness of breath is also common.4) A pleuritic chest pain, a sharp or stabbing pain, either experienced during deep breaths or coughs or worsened by them.5) People with pneumonia may cough up blood.6)experience headaches, or develop sweaty and clammy skin.

pneumonia caused by Legionella may cause abdominal pain and diarrhea, while pneumonia caused by tuberculosis or Pneumocystis may cause only weight loss and night sweats.

CauseThe symptoms of infectious pneumonia are caused by the invasion of the lungs by microorganisms and by the immune system's response to the infection The most common causes of pneumonia are viruses and bacteriaVirusesA virus reaches the lungs when airborne droplets are inhaled through the mouth and nose. virus directly kills the cells. When the immune system responds to the viral infection, even more lung damage occurs lymphocytes, activate certain chemical cytokines which allow fluid to leak into the alveoli. This combination of cell destruction and fluid-filled alveoli.Viral pneumonia is commonly caused by viruses such as influenza virus, respiratory syncytial virus (RSV), adenovirus, and metapneumovirus.

Bacteria. Streptococcus pneumoniae, often called "pneumococcus", is the most common bacterial cause of pneumonia . Bacteria enter the lung when airborne droplets are inhaled, but can also reach the lung through the bloodstream through infection in another part of the body. The neutrophils engulf and kill the offending organisms, and also release cytokines, causing a general activation of the immune system. This leads to the fever, chills, and fatigue . fluid from surrounding blood vessels fill the alveoli and interrupt normal oxygen transportation. Less common causes of infectious pneumonia are fungi, parasites & Idiopathic interstitial pneumonias (IIP) are a class of diffuse lung diseases

Pneumonia as seen on chest x-ray. A: Normal chest x-ray. B: Abnormal chest x-ray with shadowing from pneumonia in the right lung (white area, left side of image).

• Investigations• An important test for pneumonia in

unclear situations is a chest x-ray. Chest x-rays can reveal areas of opacity (seen as white) which represent consolidation.

• chest CT (computed tomography) can reveal pneumonia that is not seen on chest x-ray. X-rays can be misleading, because other problems, like lung scarring and congestive heart failure

• Sputum cultures take at least two to three days.

• Heamogram ,RFT,LFT, ect.

Differential diagnosis• . Chronic obstructive pulmonary disease (COPD) or

asthma can present with a polyphonic wheeze, similar to that of pneumonia.

• Other diseases to be taken into consideration include bronchiectasis, lung cancer and pulmonary emboli.

Complications• Respiratory and circulatory failure ,Pneumonia can also

cause respiratory failure by triggering acute respiratory distress syndrome (ARDS).

• Pleural effusion. Chest x-ray showing a pleural effusion. The A arrow indicates "fluid layering" in the right chest.

• empyema, and abscess

1. Normal AP CXR.2. Normal lateral CXR.3. AP CXR showing left lower lobe

pneumonia associated with a small left sided pleural effusion.

4. AP CXR showing right lower lobe pneumonia.

5. A lateral CXR showing right lower lobe pneumonia

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