Patients with fever not meeting these criteria, and specifically those admitted to the hospital with neither an apparent site of infection nor a noninfectious diagnosis, may be considered to have fever without localizing signs.

Abscesses:

Abdominal, brain, dental, hepatic, pelvic, perinephric, rectal, subphrenic,psoas

Infections:
Bacterial

1. Brucellosis
2. Salmonella
3. Tuberculosis
4. Bartonella henselae (cat-scratch disease)
5. Francisella tularensis,Listeria monocytogenes
6. Rat-bite fever (Streptobacillus moniliformis; streptobacillary form)
7. Others -Mycoplasma pneumoniae ,Yersiniosis, Actinomycosis , Campylobacter , Meningococcemia (chronic) -rarely
8. Localized infections- Cholangitis ,Infective endocarditis ,Mastoiditis , Osteomyelitis,Pneumonia ,Pyelonephritis ,Sinusitis

Spirochetes

1. Borrelia burgdorferi(Lyme disease),Relapsing fever (Borrelia recurrentis)
2. Leptospirosis
3. Rat-bite fever (Spirillum minus; spirillary form of rat-bite fever)
4. Syphilis

Fungal diseases
Blastomycosis (extrapulmonary) ,Coccidiodomycosis (disseminated) ,Histoplasmosis (disseminated)
Chlamydia (Lymphogranuloma venereum,Psittacosis)
Rickettsia (Ehrlichia canis ,Q fever,Rocky Mountain spotted fever ,Tick-borne typhus)

Viruses
CMV, Hepatitis viruses ,HIV, IM (Epstein-Barr virus)

Parasitic Diseases
Amebiasis , Giardiasis ,Babesiosis ,Malaria ,Toxoplasmosis
Trichinosis ,Trypanosomiasis ,Visceral larva migrans (Toxocara)

Rheumatologic diseases

1. Behçet disease
2. Juvenile dermatomyositis
3. JRA
4. Rheumatic fever
5. SLE
6. Hypersensitivity diseases-Drug fever,Hypersensitivity pneumonitis ,Pancreatitis ,Serum sickness ,Weber-Christian disease

Neoplasms

1. Atrial myxoma
2. Cholesterol granuloma
3. Hodgkin disease
4. Inflammatory pseudotumor
5. Leukemia
6. Lymphoma
7. Neuroblastoma
8. Wilms tumor

Granulomatous diseases

1. Crohn disease
2. Granulomatous hepatitis
3. Sarcoidosis

Familial-hereditary diseases

1. Anhidrotic ectodermal dysplasia
2. Fabry disease
3. Familial dysautonomia
4. Familial Mediterranean fever
5. Hypertriglyceridemia
6. Ichthyosis
7. Sickle cell crisis

Miscellaneous

1. Chronic active hepatitis
2. Diabetes insipidus (non-nephrogenic and nephrogenic)
3. Factitious fever
4. Hemophagocytic syndromes
5. Hypothalamic-central fever
6. Infantile cortical hyperostosis
7. Inflammatory bowel disease
8. Kawasaki disease
9. Periodic fevers
10. Poisoning
11. Pulmonary embolism , Thrombophlebitis ,
12. Thyrotoxicosis

Undiagnosed fever
Persistent, Recurrent, Resolved

Diagnostic Approach:

A careful history and physical examination is the first step in evaluating a patient with fever of unknown origin.
History:
Fever
o Duration, height and pattern, measurement technique
o Appearance of the child during the febrile episode
o Whether or not the fever responds to antipyretic drugs

Lack of response to NSAIDs may indicate a non-inflammatory condition as the cause of the fever
o Associated sweating
Fever, sweating and heat intolerance may indicate hyperthyroidism
Fever, heat intolerance and absence of sweating is suggestive of ectodermal dysplasia

Fever pattern:
o Intermittent:high spike and rapid defervescence-Pyogenic infection ,Can also occur in tuberculosis, lymphoma , JRA
o Remittent:fluctuating peaks and baseline that does not return to normal-Viral infections ,Can occur with bacterial infections, especially endocarditis, sarcoid, lymphoma and atrial myxoma
o Sustained: persist with little or no fluctuation-Typhoid fever, typhus and brucellosis
o Relapsing: afebrile for one or more days in between febrile episodes-Malaria, rat bite fever, Borrelia infection and lymphoma
o Recurrent: episodes of fever of more than six month’s duration-Metabolic defects,CNS dysregulation of temperature control,Periodic disorders such as cyclic neutropenia, hyperimmunoglobulin D syndrome and deficiencies of selected
Rash

Examination of the characteristics and distribution of the rash will help in the diagnosis of the cause.
A maculopapular, petechial, or urticarial rash -bacterial infections or with medication-related fever.
Viral infections -non-specific maculopapular or a petechial rash.
Many inflammatory/vasculitic disorders present with a rash.

Arthralgias –
septic arthritis and osteomyelitis;
viral infections such as infectious mononucleosis, CMV, toxoplasmosis, and tick-borne illnesses (Lyme disease or Rocky Mountain spotted fever);
medication-related reactions; or malignancies

Poor growth, poor appetite, and weight loss are observed with any chronic illness as opposed to a history that is of relatively short duration (e.g., bacterial infections).
Absent tears are observed in autonomic disease.
There may be a history of recent tick or mosquito bite with Lyme disease, Rocky Mountain spotted fever, and malaria infection.
Bone pains are present in osteomyelitis, leukemia, juvenile idiopathic arthritis (JIA), and SLE.
CNS symptoms -encephalitis, bacterial endocarditis, myocarditis, cerebral abscesses, tuberculous meningitis, secondary spread from a malignancy, severe inflammatory disorders (e.g., SLE), and cerebral malaria. Chorea is present with advanced rheumatic fever.
Urinary symptoms of dysuria, frequency, and haematuria accompany UTIs such as cystitis and pyelonephritis.

Associated complaints
o Include past or current complaints
Exposure
o Sick contacts
o Animal exposures

Household pets, domestic animals in the community and wild animals
o Travel history starting at birth

Site of travel
Prophylactic medications and immunizations for travel
Exposure to contaminated food and water while traveling
Exposure to other persons with recent travel
o Tick or mosquito bites
o Consumption of raw or undercooked meat or raw shellfish
o Consumption of dirt (pica)

Ethnic background
o Ulster Scots: nephrogenic diabetes insipidus
o Sephardic Jewish, Armenian, Turkish or Arab descent: familial Mediterranean fever , Ashkenazi Jewish descent: familial dysautonomias

Physical Exam
Careful physical exam which should be performed while the patient is febrile
Special attention to the following areas:
General appearance and vital signs
Skin and scalp
Eyes
Sinuses
Oropharynx
Lymph nodes
Abdomen
Musculoskeletal
Genitourinary

Heart rate-Tachycardia -common with fever, but persistent tachycardia may suggest thyroid storm or endocarditis/myopericarditis.
Respiration-Tachypnoea may be present in pneumonia, or multisystem disorders with lung involvement.
BP measurement
Hypertension-inflammatory/vasculitic disorders, chr pyelonephritis, SLE, and thyroid storm.
Postural hypotension -toxic shock syndromes, medication-related, and autonomic disorders.
Pallor-leukemia, lymphoma, most chronic bacterial infections and inflammatory/vasculitic illnesses, malaria, and tuberculosis.
Jaundice-Present in patients with hepatic abscess and infectious mononucleosis.
Clubbing-Present in patients with endocarditis, inflammatory bowel disease, and tuberculosis.

Lymphadenopathy
Isolated cervical lymphadenopathy -Kawasaki disease and cat-scratch disease.
Disseminated lymphadenopathy -Infectious mononucleosis, CMV, toxoplasmosis, leukemia, lymphomas, tick-borne illnesses, and some inflammatory/vasculitic illnesses.
Most bacterial infections give rise to regional lymphadenopathy.
The ulceroglandular form of tularaemia typically presents with lymphadenopathy.

Diagnostic Studies
Directed toward likely cause of fever based on information gained from the history and physical
Timing of labs and studies is based on severity of illness
For Serious cases no diagnostic test should be delayed.

CBC
o Anemia: malaria, IE, IBD, SLE or tuberculosis
o Thrombocytosis: Kawaskai disease
o WBC: atypical lymphocytes -viral infection, immature forms -leukemia , Eosinophilia-parasitic, fungal, neoplastic, allergic or immunodeficiency disorders

ESR and CRP: non-specific acute phase reactants and general indicators of inflammation Initial Tests:

Urinalysis and urine culture: UTI is a common source of FUO, sterile pyuria is suggestive of Kawaski disease or genitourinary tuberculosis

Chest X Ray: evaluate for infiltrates or lymphadenopathy

Mantoux test
Serum electrolytes, BUN, creatinine and hepatic enzymes

HIV: significant variability in manifestations of primary HIV infection

Initian Test

1.CBC ,PS,ESR, CRP
2.Aerobic blood C/S, UA, urine C/S,
3.CXR, tuberculin skin test,
4.Electrolytes, BUN, creatinine,
5.hepatic enzymes, HIV serology
Blood cultures: obtain several sets if infective endocarditis is a consideration

Additional Tests are Guided by information obtained with history, physical exam and results of initial testing

Stool studies: culture, ova and parasites in patients with loose stools or recent travel

Bone marrow: most useful in diagnosing malignancy, histiocytic disorders and hemophagocytic disease, not helpful in diagnosing infection

Serologies: targeted approach is indicated
HIV serology for all children with FUO
Syphilis is recommended for neonates, young infants and adolescents
Consider evaluation for EBV, CMV, toxoplasmosis, bartonellosis, brucellosis, tularemia as well as parasitic infections such as strongyloidiasis
Serum ANA: obtain in children over age 5 with family history of rheumatologic disease
Immunoglobulins:serum IgG, IgA and IgM in children with evidence of recurrent or persistent infections and in those with persistent fever and a negative initial evaluation
Molecular testing: (ie PCR) may be useful in specific cases
Ophthalmologic exam can be helpful to evaluate uveitis or leukemic infiltration

Imaging and other evaluations

Abdominal imaging
o Indicated if inflammatory bowel disease is suspected
o Consider if fever may be due to intrabdominal abscess -psoas abscess or cat scratch disease .

Imaging of the nasal sinuses or mastoid is recommended if sinusitis is a possible etiology for FUO

ECG/Echocardiography should be performed if there is concern for infective endocarditis

Biopsy is recommended only when there is evidence of specific organ involvement

Computed Tomography Scanning- If USG fails to help reveal the diagnosis, obtain CT scans of the abdomen in all patients with symptoms suggesting an intra-abdominal process, Intravenous pyelographymay be more sensitive than CT scanning in detecting processes involving the descending urinary tract, but CT scanning is preferred for most other processes of the retroperitoneal space.

Magnetic Resonance Imaging-osteomyelitis, vasculitides.
Endoscopic Examination
Upper and lower gastrointestinal tract, including retrograde cholangiography when indicated or when searching for Crohn disease,Whipple disease, biliary tract disease, and gastrointestinal tumors..
Radionucleotide Studies
Ventilation and perfusion radionucleotide studies to document pulmonary emboli.
A technetium bone scan may be a more sensitive method for documenting skeletal involvement when osteomyelitis is suspected in a patient in whom conventional radiography has shown no compatible changes.
Consider radionucleotide studies using gallium citrate or granulocytes labeled with indium In 111 (111In) for diagnosis of occult abscesses, neoplasms, or soft-tissue lymphomas.
Angiography, Echocardiography
Biopsy

Empiric Treatment

Approach Considerations-
Generally avoid empiric treatment with anti-inflammatory medications or antibiotics as an effort to diagnose the patient’s condition.
Empiric antibiotics can mask or delay diagnosis of infections such as meningitis, infectious endocarditis or osteomyelitis

Exceptions:
O Nonsteroidal agents in presumed JIA
O Antituberculosis drugs in critically ill children with possible disseminated TB
O Clinically deteriorating with suspicion of bacteremia or sepsis.
O Immunocompromised
Antibiotics if used should be at targeted disease rather than blancket therapy with 4-5 antibiotics.

In general, empiric therapy has little or no role in cases of classic fever of unknown origin (FUO).Treatment should be directed toward the underlying cause, as needed, once a diagnosis is made.Some studies suggest a few exceptions to this general approach, including the following:
1.Cases that meet criteria for culture-negative endocarditis
2.Cases in which findings or the clinical setting suggests cryptic disseminated TB (or, occasionally, other granulomatous infections)
3.Cases in which temporal arteritis with vision loss is suspected.

Inpatient Treatment-No evidence supports prolonged hospitalization in patients who are clinically stable and whose workup findings are unrevealing.

Outpatient Care-Conduct close follow-up procedures and systematic reevaluation studies to prevent clinical worsening. Guide further workup studies on an outpatient basis.

Patient Transfer-The need for transfer is indicated if (1) the current facility is unable to establish a diagnosis, (2) diagnostic tests are unavailable at the existing facility, or (3) the patient deteriorates clinically.

Several studies have found that prolonged, undiagnosed FUO generally carries a favorable prognosis.

The Best Approach
“ there is no substitute for observing the patient , talking to him and thinking about him”

REFERENCES-

1.Nelson Text Book of Pediatrics 18thEdition

2.Ergönül O, Willke A, Azap A, et al. Revised definition of ‘fever of unknown origin’: limitations and opportunities.J Infect. Jan 2005;50(1)

3.Cunha BA.Fever of Unknown Origin. New York, NY: Informa Healthcare; 2007

4.Pyrexia of Unknown Origin: Approach to management ,Singapore Medical Journal 2005 Vol 36: 204-208)

5.Feigin RD, Shearer WT. Fever of unknown origin in children.Curr Probl Pediatr.1976;6:1ospital.

6.Tolan, R.W. Fever of Unknown Origin: A Diagnostic Approach to This Vexing Problem. Clinical Pediatrics. 2010 49:207

7. medscape-emedicine

CHRONIC COUGH

Cough  lasting for 4 weeks or more -CHEST January 2006

1.Inflammatory disorder of airway
Asthma & Loeffler’s syndrome, Tropical eosinophilia, hypersensitivity pneumonitis.
Infection- viral, bacterial, chlamydia, mycoplasma, tuberculosis, fungal, parasitic etc.
Inhalation of environmental irritant- smoke, dust, tobacco.

2.Suppurative lung disease
Bronchiectasis, cystic fibrosis
Foreign body retained in the bronchi
Immune deficiency, dysmobility of cilia

3.Anatomic lesions
Vascular ring compressing airway; tracheal stenosis; tracheo-esophageal fistula; congenital malformations; sequestrated lobe; laryngeal web, cyst or stenosis; vocal cord paralysis; laryngotracheobronchomalacia

4.Psychogenic- habit cough

5.Post nasal discharge, sinusitis

6.Gastroesophageal reflux disease (chronic aspiration)

7.Interstitial lung disease

8.Pressure to trachea/main bronchus enlarged LN, cysts,& tumors in mediastinum. anomalous Lt. pulmonary artery
Pulmonary hemosiderosis

9.Cardiac causes
a. Pulmonary edema
b. Congestive cardiac failure
c. Pericarditis
d. Myocarditis
e. congenital heart disease

10.Drugs
a. ACE inhibitor
b. Beta antagonists

11. Abdominal Causes
a.Diaphragmatic hernia
b.eventeration of diaphragm
c. intra-abdominal masses
d.Massive ascites

Click On to Enlarge

]]> http://medchrome.com/major/paediatrics/respiratory-system/approach-child-chronic-cough-accp-guidelines/feed/ 1 http://medchrome.com/major/paediatrics/genetic-defects-paediatrics/down-syndrome-or-trisomy-21-chromosomal-disorder/ http://medchrome.com/major/paediatrics/genetic-defects-paediatrics/down-syndrome-or-trisomy-21-chromosomal-disorder/#comments Sat, 02 Jul 2011 12:34:40 +0000 Administrator http://medchrome.com/?p=1988 Trisomy 21 or  Down Syndrome was first described by John Langdon Hayden Down a Physician ( 1828-1896 AD) in The London Hospital in 1866 AD.In 1959, Lejeune and Jacobs et al independently determined -trisomy 21 as cause of Down Syndrome.

Karyotype-

1. Trisomy 21: 47 XX or XY +21 . Usually caused by an extra copy of Chromosome 21
2. Translocational type- 46 XX, der ( 14;21)(q10;q10),+21
3. Mosaic type- 46 XX/ 47 XX ,+21

Most common of the chromosomal disorders ( incidence 1 in 700 births).Risk increases with maternal age. Significant increase in risk with Maternal age above 40 years. 1:2000 in  under 25 years, 1: 300 at 35 years and 1:100 at 40 years. Co-relation with maternal age suggests that meiotic  non-disjunction of Chromosome 21 occurs in Ovum.

Male:Female ratio is 1.15:1 not much difference.

Pathogenesis

1. Meiotic non-dysjunction (95%)
2. Robertsonian translocation (4%)
3. Mosaicism due to miotic non-dysjunction during the embryogenesis. (1%) : Mosaics are people having 2 or more populations of cells within individuals.  They have variable features and milder.

Clinical features-

Severe mental retardation- most common cause of genetic mental retardation.  IQ is generally low to very low.

Facial  features :

• Mongoloid facies-flat face,low-bridged nose, epicanthal folds, mongoloid slant of eyes
• brachycephaly commonly , microcephaly, delayed closure of  fontanels, a patent metopic suture
• Absent frontal and sphenoid sinuses, and hypoplasia of the maxillary sinuses may be seen.
• low-set ears ,dysplastic ears-small ear with overfolded helix
• hypertelorism –wide set eyes
• high arched palate,open mouth with protruded and furrowed tongue ( macroglossia)

Click to view full size

Eyes-

• Brushfield spots-speckled appearance of the iris
• Cataract and squint sometimes
• Refractive error and nystagmus

Hands-

• Simian hand- short broad hands with short stubby fingers
• Simian Crease- Single palmar flexion crease.
• Clinodactyly -( Hypoplasia of the middle phalanx of 5^th finger producing incurving little finger)
• Dermatoglyphics-  more than 8 ulnar loops on fingers and distal axial triradii becomes obtuse.

Foot-

• Sandal gap- Increased gap between 1^st and 2^nd toe
• Sub-hallucial pad of fat
• Single deep longitudinal plantar crease

Cardiovascular System-Congenital heart defects- Endocardial cushion defect leads to formation of an atrioventricular canal ( a common connection between all 4 chambers), VSD, ASD, PDA

GI system – Duodenal atresia ( ‘ double bubble ‘ sign), Hirchsprung disease, tracheo-esophageal fistula, Imperforate anus.

Other System-

• Muscular hypotonia
• Broad short neck, Short height, Growth retardation
• Atlantoaxial subluxation with spinal cord compression <1 : A delay in recognizing atlantoaxial and atlanto-occipital instability may result in irreversible spinal-cord damage and add disability like visual and auditory loss.
• Infertility
• Personality- Cheerful, fond of Music.
• Premature Aging.
• Umbilcal hernia and diastasis rectii

Increase susceptibility to-

• Increased risk ( 15-20 X) of Acute Lymphoblastic Lymphoma- Trisomy 21, GATA 1 mutation and unknown genetic alternation.
• Alzheimer disease ( by age 40 virtually all will develop Alzheimer Disease)
• Coeliac disease may be associated .
• Increased susceptibility to infection (pneumonia, otitis media, sinusitis, pharyngitis, periodontal disease)
• Autoimmune hypothyroidism and Hashimoto disease
• Hyperuricemia, Diabetes Mellitus,

Prenatal Diagnosis-

1. In-utero:  Triple test using Maternal serum levels of alpha-fetoprotein, hCG, and unconjugated  estriol.
2. Ultrasonography- increased nuchal fold >4 mm, failure to visualize fetal nasal bone at age 11-13 weeks POG,femur and the humerus tend to be shortened.
3. Amniocentesis
4. Chorionic Villi sampling
5. Percutaneous umbilical blood sampling (PUBS)

Prognosis:

Down syndrome decreases prenatal viability and increases prenatal and postnatal morbidity as well. About 75%  with trisomy 21 die in fetal life.~ 85% of infants survive to age 1 year, and 50% can be expected to live longer than age 50 years. Down Syndrome is compatible to life . With good medical care , current median age at death is 47 years.

More Readings at:-

Down Syndrome: Prenatal Risk Assessment and Diagnosis
Prenatal Screening for Down Syndrome by Len Leshin, MD, FAA

Reference:

• Robbins and Cotran Pathological Basis of Disease
• Langman’s Medical embryology.
• USG measurement in down Syndrome
• Kundu Bedside Medicine
• Kaplan’s Lecture notes
• Medscape-Emedicine

Signs and symptoms of progeria

Alternative names

Hutchinson-Gilford Progeria Syndrome (HGPS)
Hutchinson-Gilford Syndrome
Progeria Syndrome

Definition

Progeria is a rare and fatal congenital disorder marked by physical symptoms resembling that of aging but having early onset in childhood. The word “Progeria” is derived from the Greek word “Progerus” meaning “prematurely old”. It has a reported incidence of about 1 in 4 – 8 million newborns. It affects both sexes equally and all races.

Cause

Point mutation in the LMNA gene that encodes the protein Lamina A which is a part of the building blocks of nuclear envelope. Hence, the production of abnormal Lamina A proteins leads to premature death of cells. It is not inherited but it is almost always a chance occurrence that is extremely rare. Progeria is related with these diseases:

• Werner’s syndrome
• Cockayne’s syndrome
• Xeroderma pigmentosum
• Scleroderma

Signs and Symptoms

Children with progeria generally appear normal at birth. By 12 months, signs and symptoms, such as skin changes and hair loss, begin to appear.

• Growth failure during the first year of life
• A narrowed face and beaked nose
• Narrow, shrunken or wrinkled face
• Alopecia (baldness, loss of eyebrows and eyelashes)
• Scleroderma like skin conditions
• Dwarfism and mental retardation
• Large head for size of face (macrocephaly)
• Small jaw (micrognathia)
• Nail and dental abnormalities
• Prominent scalp veins
• Skeletal defects with limited range of motion
• Atherosclerosis and cardiac problems

Complications

• Myocardial infarction (MI or heart attack)
• Stroke (sudden death of brain cells in a localized area due to inadequate blood flow)

Diagnosis

• On the basis of above signs and symptoms
• Blood test revealing low level of High Density Lipoprotein (HDL)
• Confirmed through genetic tests
• Earlier the diagnosis is made, treatment can be commenced to ease the signs and symptoms and prevent the possible complications like heart attack and stroke.

Treatment

Progeria is an incurable disease. Most treatment focuses on reducing possible complications. These are:

• Artery bypass surgery or angioplasty.
• Low dose aspirin.
• High calorie diet.
• Growth hormone therapy.
• Physical & occupational therapy to minimize joint stiffness and improve mobility.
• Extraction of milk teeth to provide enough space for prematurely erupting adult teeth.
• Infants who feed poorly may benefit from a feeding tube and a syringe.

Life span

Average age of 13 years with a range of about 8 – 21 years (death due to atherosclerosis)

Progeria in Nepal

No cases of progeria has been identified in Nepal by this date.

Where to donate for Progeria?

Progeria Research Foundation is a trusted foundation that conducts campaign to collect funds and aims to find the cure and effective treatment for this disease.

Go to Donate Page

Progeria as depicted in Movie “PAA”

Amitabh Bachchan as Auro who is suffering from Progeria

Amitabh Bachchan plays the 13 year old character named Auro who is suffering from Progeria. This disease rapidly accelerates his aging and towards the end of the movie by the time the character hits his teens he dies.

Main sources of information:

Mayoclinic
Medline Plus
Progeria Research Foundation