History<br />Asthma : derived from the Greek aazein, meaning "sharp breath." The word first appears in Homer's Iliad.<br />In 450 BC. Hippocrates: more likely to occur in tailors, anglers, and metalworkers. <br />Six centuries later, Galen: caused by partial or complete bronchial obstruction.<br />1190 AD, Moses Maimonides: wrote a treatise on asthma, describing its prevention, diagnosis, and treatment<br />17th century, Bernardino Ramazzini: connection between asthma and organic dust. <br />1901: The use of bronchodilators started.<br />1960s: inflammatory component of asthma was recognized and anti-inflammatory medications were added to the regimens.<br />
ASTHMA<br />Chronic inflammatory condition of the airways characterized by;<br />- airflow limitation (reversible with treatment)<br /> - airway hyper-responsivenessto a wide range stimuli<br /> - inflammation of the bronchi<br />In chronic asthma, inflammation maybe accompanied by irreversible airflow limitation<br />Symptoms are cough, wheeze, chest tightness, and shortness of breathwhich often worse at night<br />
Simple Definition<br />A reversible chronic inflammatory airway disease which is characterized by bronchial hyper-responsiveness of the airways to various stimuli, leading to widespread bronchoconstriction, airflow limitation and inflammation of the bronchi causing symptoms of cough, wheeze, chest tightness and dyspnoea.<br />
Epidemiology<br />Majority of patients(87.3%) had mild asthma; 9.9% had moderate asthma and 2.7% had severe asthma<br />Among severe asthmatics, only 19.4% were on inhaled corticosteroids<br />Common disease with unacceptably high morbidity and mortality<br />Commonly underdiagnosed and undertreated<br />Only 36.1% of adult asthmatics ever had their peak flow measured<br />Higher prevalence in rural (4.5%) than in urban areas (4%),lower educational status(5.6%) and lower income<br />
EPIDEMIOLOGY<br />The prevalence of asthma has increased 61% over the last two decades.<br />Asthma is the leading chronic illness among children.<br />Asthma results in 10 million lost school days and 3 million lost work days.<br />Deaths from asthma have increased by 31% since 1980.<br />
Classification<br />Extrinsic – implying a definite external cause<br />more frequently in atopic inviduals<br />(atopic – individual which tends to develop hypersensitivity by contact with allergens)<br />often starts in childhood - accompanied by eczema<br />Intrinsic/cryptogenic – no causative agent can be identified<br />starts in middle age<br />
Types of Asthma<br />According to the severity: helpful for treatment and management.<br />
Types of Asthma<br />According to pathophysiology<br />Allergic asthma<br />Occupational (allergic)<br />ABPA (allergic)<br />Intrinsic (Non-Allergic)<br />Exercise-induced<br />Steroid-resistant<br />
Pathogenesis<br />Complex, not fully understood<br />numbers of cells, mediators, nerves, and vascular leakage -activated by expose to allergens or several mechanism<br />Inflammation<br />Eosinophils, T-lymphocytes, macrophages and mast cell<br /> Remodeling<br />Deposition of repair collagens and matrix proteins-damage<br />Loss of ciliated columnar cells- metaplasia – increase no of secreting goblet cells<br />
Pathologic features of asthma<br />Inflammatory cell infiltration of the airways<br />Increased thickness of the bronchial smooth muscle<br />Partial or full loss of the respiratory epithelium<br />Subepithelialfibrosis<br />Hypertrophy and hyperplasia of the submucosal glands and goblet cells<br />Partial or full occlusion of the airway lumen by mucous plugs<br />Enlarged mucous glands and blood vessels<br />
Pathophysiology<br />Smooth muscle contraction<br />Thickening of airway –cellular infiltration and inflammation<br />Excessive secrection of mucus <br />Genetic factor<br />Cytokine gene complex (chromosome 5)-IL-4 gene cluster control IL-3, IL-4 , IL-5 and IL-13<br />Environment factor<br />Childhood expose irritants or childhood infection<br />
Pathophysiology<br />Extrinsic asthma: Atopic/allergic, occupational, allergic bronchopulmoaryaspergillosis.<br />Atopic or allergic<br />Dust, pollens, animal dander, food etc. Family history of atopy.<br />↑ serum IgE. <br />Skin test with Ag wheal, flare ( Classical IgE mediated response)<br />Exposure of pre-sensitised mast cells to the Ag stimulates chemical mediators from these cells. Type 1 hypersensitivity.<br />
Aetiology and triggers<br /><ul><li>Complex and multiple environmental and genetic determinant</li></ul>Genetic factors<br />Allergen exposure house dust mite, household pets, grass pollen<br />Atmospheric polutionsulphurdioxide, ozone, ciggerate smoke, perfume<br />Dietary deficiency of antioxidants vit E and selenium may protect asthma in children(freshfruits and vegetables)<br />
Aetiology and triggers<br />Occupational sensitizers<br />isocyanates(from industrial coating, spray painting)<br />colophony perfumes(electronic industries)<br />Drugs<br />NSAIDS<br />B-blocker(B1 adrenergic blocker drug such as atenolol is avoided to treat HPT and angina in asthmatic pt<br />Cold air<br />Exercise exercise-induced wheeze is driven by histamin and leukotrienes which are release from mast cells when epithelial lining fluid of the bronchi become hyperosmolar owing to drying and cooling during exercise<br />Emotion<br />
History <br />Presenting symptoms:<br />Cough ± sputum<br /> - time: become worse at night<br /> - duration: chronic / acute<br /> - associated with wheezing<br /> - fever? URTI<br />Wheeze<br /> - max during expiration and accompanied by prolonged expiration<br />
Cough History<br />1.Ask specifically about the symptoms:<br /> -Cough?how is the cough?<br /> more severe at night or on day?<br /> associated symptoms like dyspnea &<br /> wheezing?<br /> how long is the cough?<br /> Recurrent?Any previous similar episode?<br /> Aggravated factor?like cough become severe <br /> after exercise?or the cough is initiated after <br /> exercise? <br />
Cough History<br />2.If the cough is associated with dyspnea and wheezingis it relieved by bronchodilator?<br />3.Ask for any precipatating factors<br /> -whether the symptoms(cough,dyspnea,wheezing)<br /> started after exposure to weather changes, dust,<br /> exercise, infection or drugs?<br />4.Is there any pets,carpet or feather pillow in home?(easily trapped dust and the dust or animal<br /> fur will cause exacerbation of asthma)<br />
Dyspnoea History<br />Dyspnoea<br /> - onset: after exercise? cold? dust? animal fur? emotion?<br /> - severity and pattern: varies from day to day or from hour to hour<br /> - no chest pain<br />
History<br />Clinical features<br /><ul><li>Display diurnal pattern,symptoms and PEF worse in the morning
Mild intermittent asthma-asymptomatic between exacerbation
Persistent asthma-chronic wheeze and breathlessness</li></li></ul><li>History<br />5.Any history of atopy(eczema,hay fever) or allergic<br /> rhinitis?<br />6.Any family history of asthma?Any childhood asthmatics?<br />7.Whether he is a smoker or any family members is a smoker?<br />8.What is his occupation? Exposure to chemicals?<br />
History<br />Past medical history:<br />Experienced asthma attack before<br />Taking any medications: NSAIDs / β-blocker / aspirin (non atopic asthma)<br />Family history:<br />Has family history of asthma<br />
History<br />Social history:<br />Occupation: expose to fumes/organic/chemical dust<br />House: near to factory? Pets? Dust? Carpet? Feather pillow?<br />Smoking in any family members<br />
known asthmatic<br />When he was diagnosed with asthma?<br />How the asthma was diagnosed?<br />Who diagnosed it?<br />Whether he is on prophylaxis?<br />What type of prophylaxis?<br />How he get the drugs and how many dosage of the drugs?<br />Whether he know how to deliver the drugs properly?<br />How is his compliance to drugs?<br />
Physical examination<br />General inspection:<br /> - tachypnoeic, sign of respiratory distress, effort of breathing, cyanosis (life-threatening)<br />Inspection:<br />- fingers: tar staining<br /> - pulse rate: tachycardia and pulsusparadoxus, bradycardia (life-threatening)<br /> - used of accessory muscles or recession<br /> - wheezing<br />
Chest<br />Percussion:<br /> - may be hyperresonance / normal<br />Auscultation:<br /> - breath sound: vesicular<br /> - ronchi in expiratory phase, may be both in severe asthma<br /> - prolonged expiratory phase<br /> -vocal resonance decrease / normal<br />Inspection:<br /> - shape: hyperinflated in severe asthma<br /> - movement of chest/silent chest (life-threatening)<br /> - chest deformity:<br /> - recession:<br />Palpation:<br /> - chest expension may be reduce (hyperinflated)/ normal<br /> - apex beat: may be displaced<br /> -vocal fremitus: decrease<br />
Pulsusparadoxus (exaggeration of the normal variation in the pulse volume with respiration, becoming weaker with inspiration and stronger with expiration )</li></li></ul><li>Correlation<br /><ul><li>The symptoms of asthma consist of a triad of dyspnea, cough, and wheezing.
At the onset of an attack, patients experience a sense of constriction in the chest, often with a nonproductive cough.
Respiration becomes audibly harsh; wheezing in both phases of respiration becomes prominent; expiration becomes prolonged; and patients frequently have tachypnea, tachycardia, and mild systolic hypertension.
If the attack is severe or prolonged, there may be a loss of adventitial breath sounds, and wheezing becomes very high pitched.
The accessory muscles become visibly active, and a paradoxical pulse often develops.</li></li></ul><li>Diagnosing asthma<br />
Diagnosing asthma<br /><ul><li>Reversible and variable airflow limitation-as measured by a peak expiratory flow (PEF) meter in any of the following ways:</li></ul> PEF increases more than 15% and 200mls 15 to 20 minsafter inhaling a short acting beta2 agonist, or<br /> PEF varies more than 20% from morning measurement upon arising to measurement 12 hours later in patients who are taking a bronchodilator, or<br /> PEF decreases more than 15% after 6 mins of running or exercise<br />
Reversibility Test<br /><ul><li>This test is done to see whether the obstruction can be relieved by the use of a short-acting bronchodilator egsalbutamol
An improvement of 15% or more (as measured on the peak flow meter) is diagnostic of asthma.
However, in severe chronic disease or patient who has treated with long-acting bronchodilators, little reversibility will be demonstrated. </li></li></ul><li>Reversibility test<br />Forced expiratory manoeuvres before 20 minutes after inhalation of a beta-2-adrenoceptor agonist. Note the increase in FEV1 from 1.0 to 2.5 litres.<br />
Peak expiratory flow rate<br />Simple and cheap<br />Subject take full inspiration then blow out forcefully into peak flow meter.<br />Best used to monitor progression of the asthma and its treatment.<br />To access possible occupational asthma<br />PEFR value varies with sex, age and height.<br />
Peak Expiratory Flow Rate (PEFR)<br />The maximum rate of air breathed out as hard as possible through a measuring device called a peak flow meter, (after a full breath taken in). <br />Reading is measured in litres/minute (l/min). <br />Take 3 readings and choose the best <br />Reading < 80% - presense of obstruction, but not diagnostic of asthma<br />
Require to take a series of reading<br /> - on waking up<br /> - prior taking bronchodilator<br /> - after taking bronchodilator (before sleep)<br />
PEF measurements<br />During periods of well-being: provides measurement of the patients best PEF value which will provide the target for the doctor and the patient to aim for.Twice daily measurements before any inhaled bronchodilator tx will determine the diurnal variability of airway calibre.Good control of asthma means PEF variability is maintained at less than 10%.<br />During symptomatic episodes: During an attack of asthma PEF fairly accurately measures the degree of bronchospasm.A PEF of less than 50% of normal or best suggests a very severe attack and a PEF of less than 30% suggests a life-threatening attack<br />
Chest X-ray<br />Showed lung hyperinflation.<br />Not diagnostic of asthma<br />Useful to rule out other causes eg. Pneumothorax<br />-----------------------------------------------<br />Hyperinflation and increased bronchovascular markings<br />
Allergies & Atophy<br />Allergen Provocation Test<br />In suspected occupational asthma and food-allergy related asthma<br />Skin-Prick Test<br />To identify allergens<br />A drop of allergen is placed on skin , site is marked and pricked with needle, measured any weals<br />
to restore normal or best possible long term airway function
to reduce morbidity and prevent mortality </li></li></ul><li>Approach of chronic asthma<br />Education of patient and family<br />Avoidance of precipitating factors <br />Use of the lowest effective dose of convenient medications minimizing short and long term side effects. <br />Assessment of severity and response to treatment. <br />
1) Education of patient and family<br />Recognition of features of worsening asthma<br /><ul><li>increase in bronchodilator requirement
reducing peak flow rates). </li></ul>Self management plan for selected, motivated patients or parents.<br />The danger of non prescribed self medication including certain traditional medicines.<br />Natureof asthma<br />Preventive measures/avoidance of triggers <br />Drugs used and their side-effects <br />Proper use of inhaled drugs <br />Proper use of peak flow meter <br />Knowledge of the difference between relieving and preventive medications <br />
2) Avoidance of precipitating factors<br />The following factors may precipitate asthmatic attacks: <br /><ul><li>Beta blockers contraindicated in all asthmatics
Aspirin and nonsteroidal anti-inflammatory drugs if known to precipitate asthma, these drugs should be avoided.
Allergens e.g. house dust mites, domestic pets, pollen should be avoided whenever possible.
Occupation should be considered as a possible precipitating factor.
Other treatments</li></ul> Anti-histamines including ketotifen<br />AnticholinergicsExamples: Ipratropium bromide (Atrovent) <br />Methylxanthines<br /> Examples: Nuelin SR, Theodur, Euphylline<br />
Approach To Drug Therapy - "Stepwise Approach"[step 1]<br />Start at the step most appropriate to severity, moving up if needed <br />or down if control is good for > 3 months. Rescued courses of <br />prednisolone may be needed<br />STEP 1<br />MILD EPISODIC ASTHMA<br /><ul><li>Infrequent symptoms
nebulised beta2 agonist, 2-4 times a day </li></li></ul><li>Approach To Drug Therapy - "Stepwise Approach"[step 4]<br />STEP 4<br />VERY SEVERE ASTHMA<br /><ul><li>Persistent symptoms not controlled by step 3 medications </li></ul>Treatment: <br /><ul><li>as in step 3, plus oral steroids (the lowest dose possible)</li></ul>STEP DOWN<br /><ul><li>Patients should be reviewed regularly.
When the patient’s condition has been stable for 3-6 months, drug therapy may be stepped down gradually.
The monitoring of symptoms and peak flow rate should be continued during drug reduction. </li></li></ul><li>
Management of acute severe asthma<br /><ul><li>RR >50/min
B2 agonist / 02 if required</li></li></ul><li>Management Of Acute Asthma <br />Aims Of Management<br />To prevent death<br />To relieve respiratory distress <br />To restore the patient’s lung function to the best possible level as soon as possible.<br />To prevent early relapse <br />
1. Assess severe attack<br />Severe attack:<br /> a) Unable to complete sentences<br /> b) RR>25/min<br /> c) PR>110 bpm<br /> d) PEF< 50% of predicted or best<br /> Life-threatening attack:<br /> a) PEF<33% of predicted or best<br /> b) Silent chest, cyanosis, feeble respiratory effort<br /> c) Bradycardia/ hypotension<br /> d) Exhaustion, confusion, or coma<br /> e) ABG : normal/high PaCO2>5kPa (36mmHg)<br /> PaO2< 8kPa (60mmHg)<br />low pH, e.g. <7.35<br />
2. Start treatment immediately<br /><ul><li>Sit patient up & give high dose O2 in 100% via non-rebreathing bag
MgSO4 1.2-2g IV over 20 min, unless already given.
Consider aminophylline, if not already on a theophylline. Alternatively, give salbutamol IVI.</li></li></ul><li>Once patient improving…<br />Once patient is improving<br /><ul><li>Wean down and stop aminophylline over 12-24 h.
Reduced nebulized salbutamol and switch to inhaled β-agonist.
Initiate inhaled steroids and stop oral steroids if possible
Continue to monitor PEF. Look for deterioration on reduced treatment and beware early morning dips in PEF
Look for the cause of the acute exacerbation and admission</li></li></ul><li>
Follow-Up and Monitoring<br />Include review of symptoms and measurement of lung function<br /><ul><li>PEF monitoring at every visit along with review of symptoms helps in evaluating the patient’s response to therapy and adjusting tx.PEF consistently >80% of the patient’s personal best suggests good control.
Regular visits (at 1 to 6 month interval as appropriate) is essential even after control of asthma is established</li></li></ul><li>Asthma Management Plan<br /><ul><li>When PEF >80%: continue current dose of inhaled corticosteroids
When PEF 60-80%:double the dose of inhaled corticosteroids
When PEF 40- 60%:start rescue course prednisolone
When PEF persists below 60% despite rescue course prednisolone with worsening symptoms,advised to come to EMERGENCY DEPT immediately </li></li></ul><li>Management of asthma in pregnancy<br /><ul><li>In general during pregnancy,asthma becomes worse in a third of women,is stable in another third and improves in the remaining third.
Women should be reassured that their asthma medication carries less risk to the foetus than a severe asthma attack
Inadequately treated asthma can cause maternal and foetal hypoxaemia,which leads to complications during pregnancy and poorer birth outcomes</li></li></ul><li>Management: Pregnancy in asthmatics<br /><ul><li>Treatmentshould be aggressive,with the aim of eliminating symptoms and restoring and maintaining normal lung function
Beta2 agonists: No evidence of a teratogenic risk with the commonly used inhaled beta2 agonists
Ipratropium bromide: appears to be safe for use during pregnancy
Salmeterol/formoterol: not been tested extensively in pregnant women</li></li></ul><li>Management: Pregnancy in asthmatics<br /><ul><li>Theophyllines: may aggravate the nausea and GERD and can caause transient neonatal tachycardia and irritabilityTeratogenicity has been shown in animals.
Sodium cromoglycate: no adverse foetal effects
Inhaled corticosteroids: mainstay of tx in persistent asthma,good safety profile in pregnancy
Oral corticosteroids: necessary for severe asthma in pregnancy but usually only for short periods.Increased risk of cleft palate in animals given huge doses of oral steroids
Anti-leukotrienes: no data available</li></li></ul><li>Labour and Breastfeeding<br /><ul><li>Women with very severe asthma may be advised to have an elective caesarean section at a time when their asthma control is good
Breastfeeding should be continued in women with asthma
In general,asthma medications are safe during pregnancy and lactation and the benefits outweigh any potential risks to the foetus and baby</li></li></ul><li>Allergic Rhinitis and Asthma<br /><ul><li>80% of patients with asthma have allergic rhinitis
When allergic rhinitis is undetected or untreated,patients have frequent exacerbations not responding to conventional treatment
Nasal inhalation of corticosteroids are mainstay of treatment with or without oral antihistamine</li></li></ul><li>Status Asthmaticus<br />Acute exacerbation of asthma that does not respond to standard treatment of bronchodilators and corticosteroids.<br />Symptoms include chest tightness, rapidly progressive dyspnoea, dry cough and wheezing<br />The lung failure means that oxygen can no longer be provided, carbon dioxide can no longer eliminated.<br />Hence, leading to acidosis.<br />
It is not just asthma<br />Case Presentation / UMMC<br />
MIBMH<br />10.5 years old boy, known case of mild intermittent asthma presented to HSB with:<br /><ul><li>Fever, cough and runny nose ----- 1 wk.
Seen by GP and managed with oral antibiotic and symptomatic treatment but the patient did not improve.</li></li></ul><li>Review of symptoms<br />The patient is unable to lie flat for the past 2 weeks due to feeling of breathlessness.<br />
In HSB<br />respiratory distress upon admission<br />CXR:<br />mediastinal mass on right perihilar region <br />multiple cannon ball lesions in both lung fields, so <br />CT thorax, abdomen and pelvis done<br />Huge anterior mediastinalmass encasing great vessels with lung metastasis and lymphadenopathy.<br />Referred to UMMC for possibility of malignancy.<br />
Past history<br />Asthma<br />since age of 7 years <br />not on regular follow-up or treatment/prophylaxis<br />mild infrequent diurnal symptoms <br />no interference with general activity or school attendance.<br />acute exacerbation: twice a year and precipitated mainly by coldness.<br />No hospital admission<br />
Perinatal history: uneventful.<br />Developmental history: attends school, average level, very shy.<br />Immunization: full schedule.<br />Allergy: allergic to dust.<br />Family and social history:<br /><ul><li>No ill family member.
No H/O contact with T.B</li></li></ul><li>O/E<br />Looks lethargic, dyspneic RR 32/min with recessions, HR 120/min, SpO2 96% on face mask O2 5l/min, temp 36.4C <br />No lymphadenopathy.<br />Lungs: -reduced breath sounds on right medial and lower zones with crepitations on the right side<br />CVS: S1 + S2 , no murmur.<br />Abdomen: soft, liver 2cm firm.<br />
LH 11 mu/ml (H) (<0.1-6)<br />FSH 33 mu/ml(H) ( 1.2-2.5)<br />Estradiol <37 pmol/l (0-198)<br />Testosterone 2.3 nmol/l (L) (8.4-28.7)<br />DHEAS 0.5 umol/l (L) (2.2-15.2)<br />Karyotyping: 47 XXY, how many cells? Any evidence of mosaic Klinefelter? (waiting formal report).<br />
diagnosis<br />Mediastinal germ cell tumor with bilateral lung metastasis and pseudoprecocious puberty.<br />Klinefelter syndrome.<br />
Management and progress<br />Respiratory support, required BiPAP .<br />Required neb Salbutamol 4 hourly.<br />Had spikes of fever, covered with Erythromycin and Ceftriaxone.<br />After 4 days in PICU transferred to P6.<br />Started chemotherapy(UKCCSG).<br />Had NNF covered with piptazocin then imipenem and later on Ampho-B. <br />
Became neutropenic.<br />All blood and respiratory cultures have no growth.<br />
Klinefelter syndrome<br />In 1942 Klinefelter et al published a paper on 9 men with large breasts, minimal sexual and body hair, small testes and inability to produce sperms.<br />It is the most common syndrome assoc with male hypogonadism and infertility.<br />Classically 47XXY, but many variants like 48 XXXY, 48XXYY,49XXXXY,49XXXYY,50XXXXYY.<br />It is due to meiotic non-disjunction. mosaic patients may be fertile .<br />
Features<br />Hypogonadism (small testes and azoospermia-hyalinzation and fibrosis of seminiferous tubules).<br />Gynaecomestia in late puberty (30-50%) due to increase estradiol/testosterone ratio.<br />Psychosocial problems.<br />Elevated urinary gonadotrophins.<br />Mental retardation is affected by number of X chromosomes (decreased IQ 15 points for each X chromosome) [most males with 47XXY have normal intellegence, 70% have minor developmental and learning disability]<br />
Other features:<br />Pescavus, genuvalgus, fifth finger clinodactily.<br />Taurodontism (prominent molar teeth): 40% in Klinefelter, 1% in general population.<br />Radio-ulnarsynostosis---- 49XXXXY.<br />
Mortality<br />40% of conceptions with Klinefelter survive fetal period.<br />Mortality is not significantly higher in healthy individuals.<br />
Prevalence: in USA 1:500-1000<br />Race: no race difference.<br />Age: it goes undetected in most affected males until adulthood. the common indication for karyotyping is hypogonadism and infertility.<br />
investigations<br />Mid-puberty: increase FSH and LH, decrease testosterone.<br />Increase estradiol/testosterone ratio-----gynaecomastia 80%.<br />Cortisol should be checked (47% have low cortisol).<br />Decrease osteocalcin---- bone resorption.<br />Coagulation profile because of increased risk of DVT and pulm embolism.<br />Karyotyping:47 XXY 80-90 % - 10% mosaic.<br />
Primary mediastinal germ cell tumors<br />Comprise only 1-3% of germ cell tumors.<br />Overall teratoma is the most common variant, seminomais the most common malignant variant.<br />Malignant variants are uncommon and more in males.<br />Benign variants are equally disributed among males and females.<br />Testicular examination, U/S and CT are mandatory to rule out testicular primary cancer.<br />
Serum markers<br />Alpha-fetoprotein: indicates malignant non-seminomatous type.<br />BhCG: suggests trophoblastic component.<br />Malignant non-seminomatous and mixed GCTs carry worse prognosis than other GCTs.<br />
Association of M- GCTs with Klinefelter syndrome <br />Klinefelter syndrome is present in 20% of patients with M-GCT.<br />The incidence of M-GCT is 50 fold increased in patients with Klinefelter syndrome.<br />M-GCT mask the usual clinical signs of Klinefelter syndrome by inducing puberty by BhCG.<br />
Comparison of GCT between KS and general population<br />Klinefelter syndrome:<br />All contain non-seminominatous elements<br />Present at younger age (mean 17 years)<br />Precocious puberty is seen more often.<br />Almost exclusively extragonadal.<br />General population:<br />Pure seminoma is the most common malignant variant.<br />Older age at presentation (mean 29 years)<br />Precocious puberty is less often.<br />Only 2-5% extragonadal.<br />