This document discusses fever of unknown origin (FUO) in children. It begins by explaining how the body regulates temperature and what causes fevers. FUO is defined as a fever over 38.3°C for at least 8 days without diagnosis. Common causes are listed which are often infectious diseases, connective tissue diseases, and neoplasms. Specific infectious etiologies like brucellosis, cat scratch disease, and tuberculosis are explained. The diagnostic approach and evaluations for FUO are outlined including history, physical exam, initial labs, additional testing, and imaging. Empiric treatment is generally not recommended to avoid delaying diagnosis. Herbal treatments used in unconventional medicine for FUO and tuberculosis are also mentioned

1. PRESENTED BY:
SHAYAN FATIMA AZAD
ABDUL RASHED GHORI
PRESENTED TO:
PROF. DR SALEEM HASAN MUKADDAM
TABIBA HUMA SAYEED

2. 
Fever Of Unknown Origin???

3. 
The body has several ways to maintain normal body temperature. The organs
involved in helping with temperature regulation include the brain, skin, muscle, and
blood vessels.
The body responds to changes in temperature by:
 Increasing or decreasing sweat production
 Moving blood away from, or closer to, the surface of the skin
 Getting rid of, or holding on to, water in the body
 Naturally wanting to seek a cooler or warmer environment
What is Fever ???

4. 
When child has a fever, the body works the same way to control the
temperature, but it resets its thermostat at a higher temperature. The
temperature increases for a number of reasons:
 Chemicals, called cytokines and mediators, are produced in the body in response to
an invasion from a microorganism, malignancy, or other intruder.
 The body is making more macrophages, which are cells that go to combat when
intruders are present in the body. These cells actually eat-up the invading organism.
 The body is busily trying to produce natural antibodies, which fight infection. These
antibodies will recognize the infection next time it tries to invade.
 Many bacteria are enclosed in an overcoat-like membrane. When this membrane is
disrupted or broken, the contents that escape can be toxic to the body and stimulate
the brain to raise the temperature.

5.  Fever of 38.3 degree centigrade or greater of at least eight days duration, with
no apparent diagnosis after initial outpatient or hospital evaluation that includes
a careful history and physical exam and initial laboratory assessment.
 This definition may be variable to duration of 3-4 days to 3 weeks.
 A careful history and physical is the first step in evaluating a patient with fever of
unknown origin.
FUO

6. 
 Usually caused by common disorders which may have an unusual presentation.
 Most common categories are infectious disease, connective tissue diseases and
neoplasms (in order of frequency).
 A diagnosis is often never established; undiagnosed cases have become more
common in recent years.
Etiologies

7. 
Infectious

8. 
Classification According
To Etiology

9. 
Brucellosis
 Indolent infection with persistent fever and lethargy, osteoarticular complaints,
hepatosplenomegaly and mild LFT elevation.
 Consider in patients exposed to animals or animal products, especially
unpasteurized cheese.
Generalized Infections

10. 
Cat Scratch Disease
 Bartonella henselae infection.
 Often presents with lymph node inflammation; hepatosplenic involvement is
the hallmark of FUO cases.
Leptospirosis
 Clinical manifestation includes fever, rigors, myalgias, headache, cough and GI
complaints
 Occurs after exposure to animal urine, contaminated soil or water (swimming)
or infected animal tissue.
Generalized Infections

11. 
Malaria
 Caused by plasmodium species through a vector mosquito.
 Splenomegaly typically accompanies fever
 Should be considered in patients with history of travel to endemic areas, can
present months after travel.
Mycobacterial
 Extrapulmonary tuberculosis is more common than pulmonary TB.
 Careful history of possible contacts can help make the diagnosis.
 Nontuberculosis mycobacterium can cause dissemintated infection (more
common in HIV infected patients).
Generalized Infections

12. 
Salmonellosis
 Can cause typhoidal as well as localized GI illness.
 Diagnosis can be made with blood and stool cultures.
Toxoplasmosis
 Most often accompanied by cervical or supraclavicular lymphadenopathy.
 Consider with exposure to feline feces or consumption of game meat.
Generalized Infections

13. 
Tularemia
 Carried by a variety of animals and insects.
 Should be considered in children with history of animal contact, exposure to
dead wild carcasses or ingestion of rabbit or squirrel meat.
Viral Infections
 CMV, EBV, hepatitis viruses, enteroviruses and arboviruses.
 Symptoms can be non-specific and variable.
 LFTs may be elevated.
Generalized Infections

14. 

15. 

16. 
Bone and joints
 Typically present with recognizable symptoms.
 Osteomyelitis may present as FUO ; locations that are more common are
the pelvic bones, small bones and flat bones.
Infective endocarditis
 Usually occurs in setting of preexisting cardiac lesion.
 Diagnosis can be difficult: blood cultures are not always positive and
murmur may not be present
 Viridans streptococci, enterococci and staphylococci are most common
organisms.
Localized Infections

17. 
Intraabdmonial abscesses
 Patients may not have abdominal complaints at presentation
 Increased suspicion with prior intraabdominal disease, abdominal surgery or
vague abdominal pain
 Pyogenic liver abscesses are more common immunocompromised children .
Upper respiratory tract infection
 Mastoiditis, sinusitis, chronic or recurrent otitis media, chronic or recurrent
pharyngitis, tonsillitis, peri tonsillar abscess and non-specific URI have all been
reported as causes of FUO.
Urinary tract infection
 UTIs may also present with FUO.
Localized Infections

18. 
 Second most common category of FUO in children.
 Positive ANA is suggestive of a connective tissue disorder.
 Juvenile rheumatoid arthritis (juvenile idiopathic arthritis).
 Systemic presentation: high, spiking fevers, lymphadenopathy, and an
evanescent rash which may be present only when the patient is febrile
 Polyarteritis nodosa
 Systemic lupus erythematosis
Connective Tissue Disease

19. 

20. 
 Leukemia and lymphoma are the most common
malignancies that cause FUO in children.
 Neuroblastoma, hepatoma, sarcoma and atrial myxoma are
less common malignancies that may present as FUO.
Neoplasms

21. 
Leukemia
 Leukemia is carcinoma of blood forming tissues including bone marrow and
lymphatic tissues.
Lymphoma
 Carcinoma of lymphatics.
 Two types Hodgkin’s and Non Hodgkin’s.
Leukemia And Lymphoma

22. 

23. 

24. CNS dysfunction
 Severe brain damage and resulting autonomic dysfunction can be responsible for
FUO.
 Epilepsy can cause fever.
Drug fever
 Allergic reaction.
 Vaccination.
 Medication may impair thermoregulation ie phenothiazines, anticholinergic drugs
and epinephrine.
 Typically disappears within 48-72 hours of stopping medication, but can take as
long as 5-7 days or even weeks to resolve.
Other Causes

25. 
Familial dysautonomia
 Autosomal recessive disorder: autonomic and peripheral sensory nerve
dysfunction results in defective temperature regulation.
 Poor swallowing coordination, excessive salivation, diminished tearing,
excessive or diminished sweating, labile blood pressure, erythema or blanching
of the skin.
 Absence of peripheral pain sensation can lead to skin trauma.
 Impairment of deep tendon and corneal reflexes.
Other Causes

26. 
Hemophagocytic lymphohistiocytosis
 Non-malignant but life threatening disorder.
 Uncontrolled proliferation of activated lymphocytes and histiocytes leads to
hypersecretion of inflammatory cytokines.
 Manifestations: prolonged fever, hepatosplenomegaly, cytopenias.
Diabetes insipidus
 Central and nephrogenic DI can cause FUO.
Other Causes

27. 
Infantile cortical hyperostosis
 Inherited disease with persistent fevers, subperiostal bone hyperplasia and
swelling of overlying tissues
 Symptoms can include irritability and tenderness over the affected regions
 Leukocytosis, elevation of ESR and radiologic demonstration of periosteal
involvement establish the diagnosis.
Inflammatory Bowel Disease
 Fever may be more common than abdominal symptoms, especially in patient’s
with Crohn’s disease.
 Should be suspected in patients with anemia, weight loss and an elevated ESR.
Other Causes

28. 
Periodic fevers
Two most common heritable periodic fever disorders in children are familial
 Mediterranean fever and hyperimmunoglobulin D syndrome.
 FMF: autosomal recessive disorder in individuals of Mediterranean descent with
episodic fever and serosal inflammation.
 Hyperimmunoglobulin D syndrome: autosomal recessive disease with episodes of fever,
skin eruptions, abdominal complaints and joint involvement and elevated serum IgD.
Other causes

29. 
How To Evaluate The
Patient With FUO

30. 
 A careful history and physical exam is the first step in evaluating a patient with
fever of unknown origin.
Diagnostic Approach

31. Fever:
 Duration, height and pattern, measurement technique.
 Appearance of the child during the febrile episode.
 Whether or not the fever responds to antipyretic drugs.
1. Lack of response to NSAIDs may indicate a non-inflammatory condition as the
cause of the fever.
 Associated sweating:
1. Fever, sweating and heat intolerance may indicate hyperthyroidism.
2. Fever, heat intolerance and absence of sweating is suggestive of ectodermal
dysplasia.
History

32. 
Fever pattern:
 Intermittent: high spike and rapid defervescence
1. Pyogenic infection
2. Can also occur in tuberculosis, lymphoma and juvenile rheumatoid arthritis
 Remittent: fluctuating peaks and baseline that does not return to normal
1. Viral infections
2. Can occur with bacterial infections, especially endocarditis, sarcoid, lymphoma.
 Sustained: persist with little or no fluctuation
1. Typhoid fever, typhus and brucellosis

33. 
Fever pattern:
 Relapsing: afebrile for one or more days in between febrile episodes
1. Malaria, rat bite fever, Borrelia infection and lymphoma
 Recurrent: episodes of fever of more than six month’s duration
1. Metabolic defects
2. CNS dysregulation of temperature control
3. Periodic disorders such as cyclic neutropenia, hyper immunoglobulin D
syndrome and deficiencies of selected interleukin receptor sites.
 Associated complaints
1. Include past or current complaints

34. 
Fever pattern:
 Exposure
1. Sick contacts
2. Animal exposures
i. Household pets, domestic animals in the community and wild animals
3. Travel history starting at birth
i. Site of travel
ii. Prophylactic medications and immunizations for travel
iii. Exposure to contaminated food and water while traveling
iv. Exposure to other persons with recent travel
4. Tick or mosquito bites
5. Consumption of raw or undercooked meat or raw shellfish
6. Consumption of dirt (pica)
7. Exposure to medications.

35. 
 Careful physical exam which should be performed while the
patient is febrile
 Special attention to the following areas:
1. General appearance and vital signs
2. Skin and scalp
3. Eyes
4. Sinuses
5. Oropharynx
6. Lymph nodes
7. Abdomen
8. Musculoskeletal
9. Genitourinary
Physical Exam

36. 
 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, ie, patients
who are more ill should be evaluated with laboratory studies at a faster
pace than those who appear well.
Diagnostic Studies

37.  CBC and peripheral smear, ESR, CRP, Aerobic blood cultures, UA, urine
culture, CXR, tuberculin skin test, electrolytes, BUN, creatinine, hepatic
enzymes, HIV serology.
 CBC
1. Anemia: may be suggestive of malaria, infective endocarditis, IBD, SLE or
tuberculosis
2. Thrombocytosis: Kawasaki disease
3. WBC: atypical lymphocytes may suggest a viral infection, immature forms may
suggest leukemia and eosinophilia is suggestive of parasitic, fungal, neoplastic,
allergic or immunodeficiency disorders.
 ESR and CRP: non-specific acute phase reactants and general indicators of
inflammation.
Initial Diagnostics

38. 
 Urinalysis and urine culture: UTI is a common source of FUO, sterile pyuria is
suggestive of Kawasaki disease or genitourinary tuberculosis.
 Chest X Ray: evaluate for infiltrates or lymphadenopathy.
 PPD: tuberculin skin test.
 Blood cultures: obtain several sets if infective endocarditis is a consideration
 Serum electrolytes, BUN, creatinine and hepatic enzymes.
 HIV: significant variability in manifestations of primary HIV infection.
Initial Diagnostics

39. 
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
1. HIV serology for all children with FUO
2. Syphilis is recommended for neonates, young infants and adolescents
3. Consider evaluation for EBV, CMV, toxoplasmosis, bartonellosis, brucellosis,
tularemia as well as parasitic infections such as strongyloidiasis.
Additional Diagnostics

40. 
 Serum anti-nuclear antibody: 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.
Additional Diagnostics

41. 
 Abdominal imaging
1. Indicated if inflammatory bowel disease is suspected
2. Consider if fever may be due to 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.
 Ophthalmologic exam can be helpful to evaluate uveitis or leukemic infiltration.
 Biopsy is recommended only when there is evidence of specific organ involvement.
Imaging And Other
Evaluations

42. 
 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:
1. Nonsteroidal agents in children with presumed JIA.
2. Anti tuberculosis drugs in critically ill children with possible disseminated TB.
3. Patients who are clinically deteriorating and in whom bacteremia or sepsis is
strongly suspected.
4. Patients who are immunocompromised.
Empiric Treatment

43. 

44. 

45. 
HERBAL TREATMENT

46. 
Malva sylvestris (khubazi)
Atremisia absanthimum (afsantheen)
Aconitum heterophyllum (atees)
Occimum basillicum (tulsi)
Sysimbrium irio (khaksi)
Ceasalpinia bounducella (karanjwa)
Tinospora cordifolia (gilo)
FUO

47. 
 Adhatoda vasica nees (vasaka)
 Allium cepa (onion)
 Allium sativum (garlic)
 Aloe vera (aloe gel)
 Acalypha indica (acalypha)
Tuberculosis

48. 
 The aqueous extract of these plants inhibits the
enzymes and bind then inhibit those enzymes which
are essential for mycolic acid synthesis.
Mechanism of Action

49. 
 Qurs Tabasher
 Arq-e-hara bhara
 Arq-e-sher
 Qurs sher
 Qurs Tap daq
Compound Drugs Of T.B

50. 
 Artrimesia absanthimum (afsantheen)
 Swertia Chiraita (chiraita)
 Tinospora cordifolia (gilo)
 Qurs Ajamia
Malaria

51. 
 Attach with haeme with parasite free radical
endoplasmic reticulum inhibit protein synthesis
lysis of parasite.
Mechanism of Action

52. 
 Silybum marianum (Milk Thistle)
 Berberis Vulgaris (zarishk)
 Picrorhiza Kurroa (kutki)
Hepatitis

53. 
 It increase the activity of gluta-thione which has anti-
oxidant activity to prevent the damage of hepatic
cells.
Mechanism of Action

54. 
‫لئے‬ ‫کے‬ ‫استمعال‬ ‫بیرونی‬:
‫حکنول‬ ‫اور‬ ‫داخلیوں‬ ‫مرہم‬
‫شام‬ ‫و‬ ‫صبح‬:
، ‫مققشر‬ ‫السوس‬ ‫،اصل‬ ‫کاسنی‬ ‫بادیان،بیخ‬ ‫استوخودوس،پرسیاوشاں،بیخ‬(‫نیم‬
‫دینگے‬ ‫خیساندہ‬ ‫کے‬ ‫کر‬ ‫کوفتہ‬
‫انجیر‬ ‫اور‬ ‫منققی‬ ‫مویز‬ ‫ہمراہ‬
ABSCESS

55. 
Local application:
Alsi (6g) – tukhm halba (6g) – piyaz safed (9g) – namak
tawaam (2g)
ABSCESS

56. 
‫لئے‬ ‫کے‬ ‫استعمال‬ ‫بیرونی‬:
‫ناریل‬ ‫روغن‬ ، ‫کافور‬ ‫مرہم‬‫ناریل‬‫مالکر‬ ‫میں‬ ‫ہلدی‬ ‫پانی‬ ‫کے‬
‫صبح‬‫شام‬ ‫و‬:
‫جوہری‬(‫رسکپور‬+‫فلفل‬‫سیاہ‬‫عناب‬ ‫شربت‬ ‫ہمراہ‬٢‫چمچہ‬
HERPES

57. 
‫شام‬ ‫و‬ ‫صبح‬:
‫سونف‬-‫سفید‬ ‫زیرہ‬-‫زنجبیل‬-‫انجیر‬
‫غذا‬ ‫بعد‬:
‫جوارش‬‫کمونی‬ , ‫قرص‬‫تفودیہ‬
‫شب‬:
‫تنکار‬ ‫حب‬
TYPHOID

58. 
‫شام‬ ‫و‬ ‫صبح‬:
‫خطمی‬ ‫ریشہ‬ ‫لعاب‬-‫دانہ‬ ‫بیہ‬ ‫لعاب‬-‫مسلم‬ ‫اسپغول‬ ‫لعاب‬-‫ہم‬ ‫ریحان‬ ‫تخم‬ ‫لعاب‬
‫وزن‬٣‫االس‬ ‫حب‬ ‫شربت‬ ‫ہمراہ‬ ‫گرام‬
‫غذا‬ ‫بعد‬:
‫آملہ‬ ‫جوارش‬
‫شب‬:
‫مصتگی‬ ‫جوارش‬
IBD

59. 
‫شام‬ ‫و‬ ‫صبح‬:
‫نمبر‬ ‫نسخہ‬٩(‫سرخ‬ ‫صندل‬-‫شاہترہ‬-‫چرایتہ‬-‫سرپھوکہ‬-‫منڈی‬ ‫گل‬-‫عناب‬
-‫جھاؤ‬ ‫برگ‬)‫عوشبا‬ ‫شربت‬ ‫ہمراہ‬
‫غذا‬ ‫بعد‬:
‫بیش‬ ‫قرص‬
‫شب‬:
‫بادیان‬ ‫شربت‬ ‫ہمراہ‬ ‫چینی‬ ‫چوب‬ ‫معجون‬
LEISHMANIASIS

60. 
 Walnut
 Coconut oil
 Fish oil
THYROIDITIS

61. 
‫کلونجی‬
‫دانہ‬ ‫میتھی‬
‫بنفشہ‬ ‫گل‬
‫بنولہ‬
‫اسگند‬
‫سورنجاں‬
‫بابچی‬
(‫کبیر‬ ‫لبوب‬-‫بارد‬ ‫لبوب‬-‫اعظم‬ ‫لبوب‬-‫آور‬ ‫شباب‬ ‫معجون‬-‫ملکنگنی‬ ‫روغن‬
-‫الرئیس‬ ‫شیخ‬ ‫مفرح‬)
IMMUNITY BOOSTER
DRUGS

62. 
 Arq gilo
 Hab huma jadeed
 Hab rasoot
 Arq chairita
 Arq shahtra
 Hab huma
 Hab banafsha
 Laoq sapistan
COMPOUND DRUGS

63. 