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Diseases » Marburg virus » Diagnosis

Diagnosis of Marburg virus

Marburg virus Diagnosis: Book Excerpts

Tests and diagnosis discussion for Marburg virus:

Antigen-capture enzyme-linked immunosorbent assay (ELISA) testing, IgM-capture ELISA, polymerase chain reaction (PCR), and virus isolation can be used to confirm a case of Marburg hemorrhagic fever within a few days of the onset of symptoms. The IgG-capture ELISA is appropriate for testing persons later in the course of disease or after recovery. The disease is readily diagnosed by immunohistochemistry, virus isolation, or PCR of blood or tissue specimens from deceased patients. (Source: excerpt from Marburg Hemorrhagic Fever: DVRD)

Diagnostic Tests for Marburg virus: Online Medical Books

16 MEDICAL BOOKS ONLINE! Review excerpts from medical books online, free, without registration, for more information about diagnostis of Marburg virus.

PURPURA AND ABNORMAL BLEEDING: Ask the Following Questions:
(Algorithmic Diagnosis of Symptoms and Signs)

Is there a petechial rash? The presence of a petechial rash suggests either a thrombocytopenic purpura, which may be idiopathic or secondary to leukemia, aplastic anemia, collagen disease, or drugs. In addition, petechiae may suggest platelet dysfunction, in which case the platelet count will be normal, or vasculitis, such as from collagen diseases, hereditary telangiectasia, scurvy, or drugs.
Is there ecchymosis or bruises? The presence of ecchymosis or bruises would suggest hemophilia, Christmas disease, or other major coagulation defects, but it may also be related to platelet disorders or disseminated intravascular coagulation.
If there is a petechial rash, is the platelet count normal? The presence of a normal platelet count would suggest either thrombocytopathy or vasculitis.
Is there significant mucosal bleeding? The presence of mucosal bleeding along with ecchymosis and bruises suggests platelet disorders or disseminated intravascular coagulation.

DIAGNOSTIC WORKUP

If a coagulation disorder is suspected, consult a hematologist first. Routine diagnostic studies include a CBC, platelet count, sedimentation rate, blood smear for red cell morphology, urinalysis, chemistry panel, coagulation profile, rheumatoid arthritis factor, ANA test, serum protein electrophoresis, VDRL test, EKG, chest x-ray, and flat plate of the abdomen. The coagulation profile should include a platelet count, a bleeding time, a coagulation time, a partial thromboplastin time, and a prothrombin time.

If there is fever, blood cultures should be done. A bone marrow examination and bone marrow culture may be useful. If disseminated intravascular coagulation is suspected, a fibrinogen assay and estimation of fibrin degradation products should be done. Platelet function may be assessed by clot retraction tests. Spleen and liver scans and bone scans may be needed. A CT scan of the abdomen and pelvis may also be necessary. Skin, muscle, and even kidney biopsies are often done to complete the workup.

It can be seen from the above array of diagnostic tests that a hematologist should be consulted at the outset. Various forms of vasculitis may be confirmed by skin or muscle biopsy.

» READ BOOK EXCERPT ONLINE »

Source: Algorithmic Diagnosis of Symptoms and Signs, 2003

FEVER, ACUTE: Ask the Following Questions:
(Algorithmic Diagnosis of Symptoms and Signs)

Is there a history of drug ingestion or injection? This will help diagnose drug reactions and serum sickness, which are common and easily discovered in the history. Patients with glucose-6-phosphate dehydrogenase deficiency may develop fever after receiving certain drugs.
Is there a rash? The presence of a rash should make one think of a drug reaction, meningococcemia, the various exanthems, and subacute bacterial endocarditis.
Is there localized pain? If there is a sore throat, obviously streptococcal pharyngitis or a viral URI is likely. If there is headache, meningitis or encephalitis must be considered. If there is chest pain, one should consider a pulmonary infarct, myocardial infarction, or Bornholm disease. If there is abdominal pain, one would consider pyelonephritis, cholecystitis, and appendicitis among the various conditions. If there is joint pain, one should consider rheumatic fever, rheumatoid arthritis, or septic arthritis.
Is there a focal discharge? A productive cough would make one consider pneumonia. A rectal discharge would make one consider a perirectal abscess. A urethral discharge should make one think of gonorrhea.
Are there other localizing signs? Frequency of urination should make one think of pyelonephritis. A productive cough should make one think of pneumonia, whereas jaundice would make one think of hepatitis.

DIAGNOSTIC WORKUP

Routine studies include a CBC, sedimentation rate, chemistry panel, urinalysis, chest x-rays, VDRL test, and tuberculin skin test. Serial blood cultures should be done on all patients. Febrile agglutinins usually should be done. An ASO titer or streptozyme test should be done to exclude rheumatic fever. RNA, ANA, and DNA tests should be done to look for lupus and other connective tissue disease. An HIV antibody titer may need to be ordered.

The next step is to culture any discharge or various body fluids that might be suspect. Thus, a urinalysis and urine culture should be done. A nose and throat culture should be done. A sputum smear and culture may need to be done. The next consideration is to do various serologic tests. A heterophile antibody titer should be done in teenagers. Febrile agglutinin tests may need to be done. Acute and convalescent phase sera for viral studies may need to be done.

Next one should do skin testing. Thus, histoplasmin, coccidioidin, and blastomycin skin testing should be done on patients with a cough. Trichinella skin testing may need to be done, as well as brucellin skin testing. A Kveim test might need to be done for suspected sarcoidosis.

The next step is to do plain x-rays of suspected areas. For instance, x-rays of the teeth may disclose an abscessed tooth. X-rays of the long bones may disclose a metastatic carcinoma.

The next step is contrast x-ray studies of various organ systems. An intravenous pyelogram may show a hypernephroma. A cholecystogram may show gallstones. An upper GI series and barium enema may show chronic pancreatitis or diverticulitis. Angiography may disclose periarteritis nodosa, aortitis or giant cell arteritis.

The next step is to do a CT scan of the abdomen and pelvis. If this is negative, consider a CT scan of the chest and mediastinum. Echocardiography may disclose valvular vegetations or an atrial myxoma.

Next, consider biopsying various organ systems. For instances, a lymph node biopsy may disclose a lymphoma or sarcoidosis. A muscle biopsy may disclose periarteritis nodosa, polymyositis, or trichinella.

Next one should do bone scans and gallium scans for possible metastasis, osteomyelitis, or localized abscesses.

If all these procedures fail to turn up a lesion, then an exploratory laparotomy may need to be done. A fibrin test may indicate Mediterranean fever, or urine for etiocholanolone may also indicate a relapsing type of fever. A urine test for porphobilinogen may diagnose porphyria.

The wisest move is to conduct this investigation with the help of an infectious disease specialist or a specialist in the body organ system most likely suspected of harboring the infection.

» READ BOOK EXCERPT ONLINE »

Source: Algorithmic Diagnosis of Symptoms and Signs, 2003

FEVER, CHRONIC: Ask the Following Questions:
(Algorithmic Diagnosis of Symptoms and Signs)

Is there a history of drug ingestion or injection? Of course, the history should reveal that the patient has been on a certain drug or has received certain antitoxins, serums, or vaccines.
Is there a rash? If there is a rash, one should suspect subacute bacterial endocarditis, Rocky Mountain spotted fever, secondary syphilis, rat-bite fever, pemphigus, a drug reaction, lupus erythematosus, dermatomyositis, or typhoid fever. There are other conditions associated with a rash also.
Is there a characteristic pattern to the fever? The various forms of malaria give a characteristic pattern of the fever, as well as undulant fever in Hodgkin's disease.
Is there localized pain? Abdominal pain should suggest a cholecystitis, hepatic abscess, diverticulitis, etc. A sore throat should suggest infectious mononucleosis, leukemia, and subacute thyroiditis. Joint pain should suggest rheumatoid arthritis, rheumatic fever, or gonococcal arthritis. Earache should suggest otitis media or mastoiditis. Chest pain should suggest tuberculosis, pleurisy, or empyema.
Is there a localized discharge? Purulent sputum should suggest pneumonia, tuberculosis, or chronic fungal disease in the lung. A urethral discharge would suggest gonorrhea or Reiter's disease.
Is there a localized mass or swelling? An abdominal mass would suggest hepatic abscess, pancreatic cyst, or diverticular abscess. A flank mass might suggest hypernephroma or perinephric abscess.

DIAGNOSTIC WORKUP

The diagnostic workup is similar to that for acute fever on page 168 .

» READ BOOK EXCERPT ONLINE »

Source: Algorithmic Diagnosis of Symptoms and Signs, 2003

Fever: Differential Diagnosis
(In a Page: Signs and Symptoms)

Infection is the most common cause
–Viral (e.g., influenza, HIV, hepatitis, herpes simplex encephalitis, mononucleosis, adenovirus)
–Bacterial (e.g., pneumonia, endocarditis, tuberculosis, meningitis, pyelonephritis, appendicitis, cholecystitis, cellulitis)
–Lyme disease
–Malaria
–Syphilis
–Tularemia
–Intra-abdominal abscess

Malignancy
–Lymphoma (Hodgkin's and non-Hodgkin's)
–Lymphoproliferative disorders
–Renal cell carcinoma
–Leukemia
–Hepatocellular carcinoma
Rheumatologic disorders
–Temporal arteritis/giant cell arteritis
–Adult-onset Still's disease
–Systemic lupus erythematosus
–Sarcoidosis
–Rheumatoid arthritis
Drug fever
–Often temporally associated with the initiation of a new medicine
–Often associated with a rash (biopsy reveals leukocytoclastic vasculitis)
–Eosinophilia is common

Pulmonary embolism
–Mild fever is often present
–Other findings of thromboembolic disease (e.g., leg swelling, dyspnea) may be present

Osteomyelitis

Occult abscess

Malignant hypothermia

Workup and Diagnosis

Complete history and physical examination
–In most cases, the cause of fever will be suggested during the history and physical
–Note characteristics of the fever, maximum temperature, presence of diurnal variation, and recent travel
Initial laboratory studies may include CBC with differential, electrolytes, BUN/creatinine, glucose, calcium, urinalysis, urine cultures, liver function tests, and ESR
Blood cultures, including thick smear of the blood to evaluate for parasites (e.g., malaria)
Chest X-ray may reveal focus of infection (e.g., pneumonia, tuberculosis, malignancy)
Lumbar puncture for CSF analysis may be indicated
CT scan of chest and abdomen may reveal an occult infection, abscess, or malignancy
Echocardiogram is indicated if suspect infective endocarditis or aortitis (syphilis)
Tagged white cell scans may be used to localize abscess
Bone marrow biopsy may be indicated if leukemia or a myelodysplastic syndrome is suspected

» READ BOOK EXCERPT ONLINE »

Source: In a Page: Signs and Symptoms, 2004

Purpura: Differential Diagnosis
(In a Page: Signs and Symptoms)

Palpable purpura (papules or nodules that are red/purple and do not blanch with pressure)

Leukocytoclastic Vasculitis
–A necrotizing vasculitis of small vessels
–Fever, malaise, fatigue and arthralgias
–Inciting factors include drugs (e.g., NSAIDs, thaizides, and phenothiazines), infection [bacterial (e.g., RMSF, meningococcemia) or viral (e.g., hepatitis)] or, blood abnormalities (e.g., cryoglobulinemia, cryofibrinogenemia)
–Vasculitic injury to kidneys, brain, lung, heart, and GI tract may occur

Collagen vascular diseases
–Systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis
Granulomatous vasculitis (e.g., Wegener's, Churg-Strauss syndrome)
Polyarteritis nodosa
Internal malignancies
–Myeloma, lymphoma, or leukemia
Henoch-Schönlein purpura

Drugs
–Aspirin, NSAIDs, warfarin, heparin
Nonpalpable purpura (flat macules, patches
similar to ecchymoses; or petechiae that do not blanch with pressure)
Trauma
Advancing age (senile purpura)
Actinic changes
Chronic stasis
Coagulopathies (affecting platelet number or function)
–TTP (pentad of fever, microangiopathic hemolytic anemia, thrombocytopenia, renal insufficiency, and neurologic signs)
–ITP
–Drug-induced thrombocytopenia
–Bacteremia and many viral diseases

Scurvy (vitamin C deficiency) can cause hemorrhage and purpura
TORCH infection can cause congenital purpura (“blueberry muffin baby”)
Many systemic diseases (e.g., Cushing's and diabetes have associated nonpalpable purpura)

Workup and Diagnosis

History and physical examination
–History of present illness, past medical history, illness exposure, medication history, and a complete review of systems including systemic symptoms (e.g., arthralgias, myalgias, fever), characteristic spread patterns (e.g., RMSF usually starts peripherally and spreads centrifugally onto the trunk), and CNS symptoms (may suggest SLE or meningococcemia)
–Focused physical examination with complete skin exam and notation of palpable versus nonpalpable rash

Initial laboratory evaluation includes CBC with differential and PT/PTT/INR (to rule out coagulopathy), urinalysis (evaluate for hematuria in HSP), LFTs (to evaluate for hepatitis), BUN/creatinine (evaluate renal insufficiency (which may occur in PAN, HSP, SLE, and many other palpable purpura-inducing diseases), ESR and/or C-reactive protein (to evaluate for collagen vascular disease)
Blood cultures and consider skin cultures by a punch biopsy if the patient is febrile
ANA and rheumatoid factor titers and a viral hepatitis screen may be indicated
Age-appropriate malignancy screening
Punch biopsy is diagnostic for leukocytoclastic vasculitis

» READ BOOK EXCERPT ONLINE »

Source: In a Page: Signs and Symptoms, 2004

Rash with Fever: Differential Diagnosis
(In a Page: Signs and Symptoms)

Viral exanthems
–Leading cause of fever and rash in childhood
–Most children present with low-grade fevers, viral prodromal symptoms, and a secondary diffuse exanthem that is usually nonspecific and morbilliform
–Often last only a few days and requires only supportive management
Drug reactions
–Account for a large portion of rashes with associated fever
–Immune complex disease or serum sickness has been reported with many medications
Meningococcemia
–Most common under age 1
–After a brief prodrome; onset is abrupt with spiking fevers, diffuse purpuric lesions, delirium, and death
–DIC and purpura fulminans with secondary necrosis of digits and limbs can occur

Rocky Mountain Spotted Fever
–A fulminant and deadly rickettsial disease transmitted by a tick bite
–Only 60% of patients are aware of tick bite
–Characteristic rash starts acrally on wrists and ankles and spreads toward the trunk
–Initially, pink macules evolve over 10–24 hours into red papules, then purpuric macules and violaceous patches involving most of the body surface area
–Necrosis and DIC may occur
Toxic shock syndrome, Staphylococcus aureus, and streptococcal diseases
–Most cases due to toxin production
–Rapid onset of fever, hypotension with generalized skin (palms and soles common) and mucous membrane erythema (“erythroderma” in case definition), and subsequent multiorgan failure
–Palmar/solar desquamation in 1–3 weeks
–A morbilliform rash and skin “pain” or hyperesthesia is common
–Nonsurgical and surgical wounds are often the source of infection in the more common nonmenstrual variant of TSS

Fifth disease
Measles
Rubella
Parvovirus
Varicella

Workup and Diagnosis

Because of a seemingly endless list of possible etiologies for fever and rash, a focused history and physical exam are essential to a quick, accurate diagnosis
Determine whether the patient appears toxic; age and presence of co-morbid conditions aid diagnosis
If there is any evidence of purpura;
–Quickly consider the diagnosis of RMSF, meningococcemia, or systemic vasculitis
–In the cases of meningococcemia and RMSF, the diagnosis must be made empirically, then later confirmed so that therapy is immediately initiated

Obtain bacterial cultures from any wounds, culture the pharynx if indicated, and consider skin biopsy and culture; blood cultures are indicated in toxic patients; consider immediate lumbar puncture for CSF culture and Gram stain if meningococcemia is suspected

Acute and convalescent antibody titers can confirm RMSF; skin biopsy with immunofluorescnce may demonstrate a vasculitis with visible rickettsial organisms within the endothelium

TSS is often diagnosed by history and examination alone; recent cutaneous injury and nonspecific morbilliform rash in a hypotensive patient in association with the presence of epidermal necrosis on skin biopsy can confirm the diagnosis; wound cultures with growth of staph or strep

» READ BOOK EXCERPT ONLINE »

Source: In a Page: Signs and Symptoms, 2004

Purpura: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

Vasculitis (palpable purpura)
–HSP: Most common vasculitis, incidence: 0.01%, in 50% follows URI; other triggers are bacterial infection, drugs, vaccines, food, insect bites; lasts 1–2 weeks, age 2–8 (mean 4 years), M > F, IgA-mediated, small vessels
–Polyarteritis nodosa (PAN), Wegener granulomatosis (WG): Rare in children

Hematologic
–ITP: Age 1–5 years; autoantibodies against platelets (platelets destroyed by splenic macrophages); usually 1–6 weeks after viral infection; 70–80% acute self-limited; 10–20% chronic recurrent; <1% associated with intracranial hemorrhage
–Other causes of thrombocytopenia: Wiscott-Aldrich syndrome, aplastic anemia, leukemia, disseminated intravascular coagulation (DIC), thrombocytopenia absent radius (TAR)

Coagulation factor deficiencies:
–Hemophilia A/B (factors VIII/XI): A (1/7,500 male births) four times more common than B; X-linked recessive
–vWD: Prevalence 1%, autosomal dominant, vW factor deficiency or decreased function
–Liver disease: Decreased production of coagulation factors
–Hemorrhagic disease of the newborn: Decreased vitamin K-dependent coagulation factors (II, VII, IX, X)

Infections
–Bacterial/rickettsial: Meningococcemia (MC), Group A strep (scarlet fever), Streptococcus viridans/Staphylococcus aureus (endocarditis), Gonococcus (disseminated), Leptospirosis, Rickettsia rickettsii (Rocky Mountain spotted fever), R. prowazekii (epidemic typhus), Ehrlichiosis
–Viral: Hepatitis B, Dengue hemorrhagic fever, atypical measles

Drugs: Coumadin, heparin, aspirin, thiazide, corticosteroids, penicillins, sulfonamides
Others: Trauma/abuse, scurvy (vitamin C deficiency)

Workup and Diagnosis

Determine location, duration, associated/preceding symptoms, family history of bleeding disorders, social history (for abuse), insect bites, travel history, drugs, easy bruising; meningeal signs; purpura fulminans
HSP: Purpura mostly on buttocks and legs; arthritis, abdominal pain, ±GI hemorrhage, renal disease, self-limited; complications: intussusception, end-stage renal disease <1%; increased platelet/ESR/WBC/IgA
ITP: Sudden petechiae/ecchymoses, epistaxis, or menorrhagia; rare splenomegaly; platelet count usually <20,000; bone marrow exam if other marrow disease is suspected
MC: Septic shock, ±meningitis; culture and Gram stain (blood and CSF)
Hemophilia A/B: Easy bruising, intramuscular hematomas, hemarthroses, B milder than A; mild: 5–30%, moderate: 1–5%, severe: <1% of normal factor level
vWD: Petechiae/ecchymoses, epistaxis, menorrhagia
Endocarditis: Janeway lesions, splinter hemorrhages
PAN/WG: Painful skin nodules, any organ (PAN); skin, kidneys (glomerulonephritis), pulmonary hemorrhage (WG); biopsy; angiography in WG (for aneurysms)
Atypical measles: clinical diagnosis, history of killed vaccine + exposure
DIC: Increased PT/PTT, decreased platelets, increased FDP/D-dimers, hemolysis

>>>>

» READ BOOK EXCERPT ONLINE »

Source: In A Page: Pediatric Signs and Symptoms, 2007

Fever – Cyclic: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

PFAPA, or Marshall syndrome
–Periodic fever (usually high, 104°F [40°C]), aphthous stomatitis, pharyngitis, and adenitis
–Most common diagnosis for true cyclic fever, usually in children <5 years
–Recurs every 3–4 weeks

Cyclic neutropenia
–Periodic fever, average cycle of 21 days
–Pharyngitis, mouth ulcers, and lymphadenopathy are also noted
–May not be associated with infection

Infectious diseases
–Relapsing fever due to Borrelia recurrentis,
relapses every 10–14 days
–EBV may occur at 6–8 week intervals

Familial Mediterranean fever
–Brief attacks of fever and serositis
–Autosomal recessive disease
–Sephardic Jews, Arabs, Turks, and Armenians commonly affected
–50% have onset before 10 years of age
–May occur in regular 7–28-day intervals
–Amyloidosis is a possible complication

Hyper-IgD and periodic fever syndrome (HIDS)
–High fevers, abdominal pain, cervical lymphadenopathy, sometimes diarrhea and arthritis, in early infancy
–Autosomal recessive, most patients from Western Europe (French, Dutch)
–Cycles may be regular every 14–28 days
- TNF-receptor-associated periodic syndrome (TRAPS) or Hibernian fever
  –Fever, myalgias with migratory pattern, conjunctivitis and rash
  –Autosomal dominant
  –first described in Irish/Scottish individuals but other ethnic groups involved
  –Amyloidosis is a possible complication (25% of untreated individuals)
- Factitious fever
Workup and Diagnosis
- History
  –Age of onset, duration of episodes, duration of symptom-free periods, associated symptoms (pharyngitis, aphthous ulcers)
  –Lymphadenopathy, abdominal pain
  –Family history of cyclic fever, ethnicity
  –Exposure to ticks (woods, camping), travel history
>

» READ BOOK EXCERPT ONLINE »

Source: In A Page: Pediatric Signs and Symptoms, 2007

Fever – Recurrent: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

Repeated viral infections
–Most common cause of recurrent febrile episodes in childhood
–Start of day care or change of geographic location may be related

Urinary tract infection (UTI)
–May be self-limited but recur especially if underlying anomaly exists

Epstein-Barr virus (EBV)
–May present with recurrent febrile episodes due to one initial infection

Other specific viral syndromes
–Parvovirus B19
–CMV

Immunodeficiency
–Repeated bacterial infections should lead to investigation of immune status

Dental abscess (non-dental abscesses typically present with prolonged daily fever)
Chronic meningococcemia
Acute rheumatic fever
Inflammatory bowel disease (IBD)
Juvenile rheumatoid arthritis (JRA)
Behçet disease

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) or Hibernian Fever
–Autosomal dominant disease with fever, myalgias with migratory pattern, conjunctivitis and rash

Familial cold autoinflammatory syndrome or familial cold urticaria
–Rash, fever, arthralgia, and conjunctivitis
–Precipitated by exposure to cold

Muckle-Wells syndrome
–Similar presentation to familial cold urticaria
–Symptoms not triggered by cold

Brucellosis
–Most prevalent around the Mediterranean and Arabic countries, also present in South America and India

Yersiniosis
Typhoid fever
Rat-bite fever
Malaria
Factitious fever

Workup and Diagnosis

History
–Documentation of fever
–Duration of episodes and fever-free intervals
–Symptoms associated with the fever
–Symptoms during the fever-free intervals
–Weight loss
–Recent documented infections, medications
–Travel, animal and insect exposure
–Specific conditions related to episodes (e.g., cold)

Physical exam
–Vitals, growth parameters (failure to thrive can be a presentation of UTI and immunodeficiency)
–Rash (transient pink rash in JRA)
–Ophthalmologic exam: Uveitis (IBD and Behçet), conjunctivitis (TRAPS)
–Hepatosplenomegaly, lymphadenopathy
–Genital ulcers (Behçet)
–Perianal skin tags (IBD)
–Mouth ulcers, pharyngitis
–Arthritis

CBC with differential
ESR or CRP
Urine culture
Blood culture
Serology for EBV, CMV, or Parvovirus B19
Low levels of serum type 1 TNF receptor in TRAPS
Documentation of fever in the office should exclude the possibility of factitious fever

» READ BOOK EXCERPT ONLINE »

Source: In A Page: Pediatric Signs and Symptoms, 2007

Fever – Unknown Origin: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

Infections (40%)
–Infectious mononucleosis (EBV, CMV)
–Other systemic viral syndromes (e.g., HIV)
–UTI (e.g., E. coli)
–Osteomyelitis (e.g., staphylococcus)
–Upper and lower respiratory infections (sinusitis, mastoiditis, pneumonia)
–Cat-scratch disease (Bartonella henselae)
–Tuberculosis, nontuberculous mycobacterial infections
–Abscess (abdominal or retroperitoneal)
–CNS infections
–Endocarditis (subacute)
–Salmonellosis
–Lyme disease (Borrelia burgdorferi)
–Leptospirosis
–Congenital syphilis
–Others: Brucellosis, histoplasmosis, leishmaniasis, yersiniosis, Q fever (Coxiella burnetii), Rocky Mountain spotted fever (Rickettsia rickettsii)

Autoimmune diseases (15%)
–Rheumatoid arthritis accounts for 3/4 of FUO due to autoimmune diseases
–Systemic lupus erythematosus
–Rheumatic fever
–Vasculitis (e.g., HSP)
–Sarcoidosis

Neoplastic diseases (7%)
–Leukemia/lymphoma accounts for 80% of
FUO due to malignancies
–Neuroblastoma
–Hepatoma
–Soft tissue sarcoma

Inflammatory bowel disease (3%)
Drugs and nutritional supplements (drug fever)
Factitious fever
Munchausen by proxy
Neurologic disorders
–Familial dysautonomia
–Central thermoregulatory disorder
–Head injury
Hyperthyroidism
Anhidrotic ectodermal dysplasia
Diabetes insipidus
Kikuchi disease

Workup and Diagnosis

History
–Differentiate between FUO and multiple febrile
illnesses that occur in short period of time
–Daily documentation of fever, onset, duration
–Weight loss, diet history, medications, sick contacts
–Animal or tick exposure, travel, foreign contacts
–Immune status, history of transfusion, surgery
–FH of autoimmune or neoplastic diseases

Physical exam
–Vital signs, growth parameters
–Skin (rash, desquamation, jaundice)
–Ophthalmologic exam (conjunctivitis, uveitis)
–Oral lesions
–Cardiologic exam (new onset murmur)
–Abdominal exam (masses, hepatosplenomegaly)
–Testicular exam
–Muscle tenderness, bone tenderness, arthritis
–Lymphadenopathy
–Neurologic exam

Labs
–CBC, ESR, C-reactive protein
–Renal and hepatic function tests, albumin and globulin
–Urinalysis, blood and urine culture
–Viral titers, PPD, cultures for specific organisms, ASO, ANA, bone marrow

Radiographic imaging with plain films, ultrasound, bone scan, CT scan or MRI of specific organ systems as warranted by the history and physical exam

» READ BOOK EXCERPT ONLINE »

Source: In A Page: Pediatric Signs and Symptoms, 2007

Fever – Acute: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

Viral infections
–Account for the majority of febrile illnesses (FI) in infancy and childhood
–Upper respiratory infections (e.g., parainfluenza virus)
–Lower respiratory infections (e.g., RSV)
–Non-bacterial gastroenteritis (e.g., rotavirus)
–Aseptic meningitis (e.g., enterovirus)

Bacterial infections
–UTIs account for 1.7% of FI in children 5 years and 7.5% in infants <8 weeks
–Pneumonia (e.g., group A streptococcus)
–Bacteremia (2% of FI in all children, highest rates seen in younger infants)
–Meningitis (0.8% of FI in all children)
–In febrile neonates, the overall rate of serious bacterial infections (SBI) is ~13%
Vaccine reaction
- Collagen vascular diseases
  –Kawasaki disease: 3,000 cases per year in the U.S., rates higher in Asia, 80% of cases occur in children <5 years
  –Henoch-Schönlein purpura: Low-grade fever is present in 50% of cases
  –Juvenile rheumatoid arthritis: Incidence 1/10,000
  –SLE
  –Acute rheumatic fever
- Malignancy
  –Leukemia: Most common childhood malignancy; early symptoms include fever, fatigue, pallor, anemia, bone pain
  –Lymphoma
  –Solid tumors (neuroblastoma, sarcoma)
- Inflammatory bowel disease
  –Diarrhea, pain, fever, blood loss
  –Crohn disease, ulcerative colitis
- Tissue injury (trauma, hematoma, burns)
- Drug reaction
- Biologic agents (blood products, gamma-globulin)
- Endocrinologic disorders
  –Thyrotoxicosis
  –Pheochromocytoma
- Genetic diseases
  –Familial Mediterranean fever
- Factitious fever
Workup and Diagnosis
- Physical exam
  –Temperature: Rectal preferred for infants <3 months
  –Vitals: Relative brady- or tachycardia, tachypnea
  –Growth parameters especially if frequent febrile episodes/infections (immunodeficiency)
  –Appearance, irritability, quality of cry, consolability
  –Skin (color, rash, desquamation), conjunctivitis, ocular or nasal discharge, mouth lesions, throat and ear exam
  –Lymphadenopathy, abdominal exam, neuro exam
  –Joint exam (arthritis), muscle tenderness
  - Immunologic workup and/or bone marrow for prolonged fever and/or other clinical evidence
  >>>>

» READ BOOK EXCERPT ONLINE »

Source: In A Page: Pediatric Signs and Symptoms, 2007

FEVER: Approach to the Diagnosis
(Differential Diagnosis in Primary Care)

There are certain things to remember when a patient with fever is approached. First, a mild elevation up to 100.5°F (38°C) rectally may be normal in some people. Second, one should rule out malingering by the patient or incorrect recording by hospital personnel. Finally, psychogenic disorders must be ruled out.

The duration and severity of the fever are important. If possible, a careful chart of the fever should be made with the patient off all drugs (especially aspirin and steroids). Conditions with intermittent or relapsing fever such as brucellosis, malaria, and Mediterranean fever will be elucidated in this fashion (Table 28).

The association with other symptoms is important. Fever, right upper quadrant pain, and jaundice suggest cholecystitis or cholangitis, whereas fever with right-sided flank pain suggests pyelonephritis. After taking a few moments to jot down the differential before launching into the history and physical examination, one can question and examine the patient more appropriately. The differential diagnosis will also lead to more appropriate use of laboratory testing.

» READ BOOK EXCERPT ONLINE »

Source: Differential Diagnosis in Primary Care, 2007

Fever: History and physical examination
(Handbook of Signs & Symptoms (Third Edition))

If the patient’s fever is only mild to moderate, ask him when it began and how high his temperature reached. Did the fever disappear, only to reappear later? Did he experience other symptoms, such as chills, fatigue, or pain?

Obtain a complete medical history, noting especially immunosuppressive treatments or disorders, infection, trauma, surgery, diagnostic testing, and the use of anesthesia or other medications. Ask about recent travel because certain diseases are endemic.

Let the history findings direct your physical examination. Because a fever can accompany diverse disorders, the examination may range from a brief evaluation of one body system to a comprehensive review of all systems. (SeeHow fever develops.)

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Source: Handbook of Signs & Symptoms (Third Edition), 2006

Purpura: History and physical examination
(Handbook of Signs & Symptoms (Third Edition))

Ask the patient when he first noticed the lesion and whether he has noticed other lesions on his body. Does he or his family have a history of bleeding disorders or easy bruising? Find out what medications he’s taking, if any, and ask him to describe his diet. Ask about recent trauma or transfusions and the development of associated signs, such as epistaxis, bleeding gums, hematuria, and hematochezia. Also ask about systemic complaints that may suggest infection, such as a fever. If the patient is female, ask about heavy menstrual flow.

Gender Cue: Purpura is more common in women and particularly in individuals with large areas of subcutaneous fat, such as the breasts, abdomen, buttocks, thighs, and calves.

Inspect the patient’s entire skin surface to determine the type, size, location, distribution, and severity of purpuric lesions. Also inspect the mucous membranes. Remember that the same mechanisms that cause purpura can also cause internal hemorrhage, although purpura isn’t a cardinal indicator of this condition.

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Source: Handbook of Signs & Symptoms (Third Edition), 2006

Allergic purpuras: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

No laboratory test clearly identifies allergic purpura (although white blood cell count and erythrocyte sedimentation rate are elevated). Diagnosis therefore necessitates careful clinical observation, in many cases during the second or third attack. Except for a positive tourniquet test (a test to assess the capillaries’ability to withstand increased pressure), coagulation and platelet function tests are usually normal. Small-bowel X-rays may reveal areas of transient edema; in many cases, tests for blood in the urine and stool are positive. Increased blood urea nitrogen and creatinine levels may indicate renal involvement. Diagnosis must rule out other forms of nonthrombocytopenic purpura.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Colorado tick fever: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

CONFIRMING DIAGNOSIS A history of recent exposure to ticks along with moderate to severe leukopenia, complement fixation tests, or virus isolation confirm the diagnosis.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Idiopathic thrombocytopenic purpura: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

Platelet count less than 20,000/µl and prolonged bleeding time suggest ITP. Platelet size and morphologic appearance may be abnormal; anemia may be present if bleeding has occurred. As in thrombocytopenia, bone marrow studies show an abundance of megakaryocytes and a shortened circulating platelet survival time (hours or days). Occasionally, platelet antibodies may be found in vitro, but this diagnosis is usually inferred from platelet survival data and the absence of an underlying disease.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Lassa fever: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

CONFIRMING DIAGNOSIS Isolation of the Lassa virus from throat washings, pleural fluid, or blood confirms the diagnosis.

Recent travel to an endemic area and specific antibody titer support the diagnosis.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Relapsing fever: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

CONFIRMING DIAGNOSIS Diagnosis requires demonstration of the spirochetes in peripheral blood smears during febrile periods, using Wright's or Giemsa stain.

Borrelia spirochetes may be more difficult to detect in later relapses because their number declines in the blood. In such cases, injecting the patient's blood or tissue into a young rat and incubating the organism in the rat’s blood for 1 to 10 days commonly allows spirochete identification.

In severe infection, spirochetes are found in the urine and cerebrospinal fluid. Other abnormal laboratory results usually include a white blood cell (WBC) count as high as 25,000/µl, with increases in lymphocytes and erythrocyte sedimentation rate; however, the WBC count may be normal. Because the Borrelia organism is a spirochete, relapsing fever may cause a false-positive test for syphilis in 5% to 10% of cases.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Rheumatic fever and rheumatic heart disease: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

Diagnosis depends on recognition of one or more of the classic symptoms (carditis, rheumatic fever without carditis, polyarthritis, chorea, erythema marginatum, or subcutaneous nodules) and a detailed patient history. Laboratory data support the diagnosis:

❑ White blood cell count and erythrocyte sedimentation rate may be elevated (during the acute phase); blood studies show slight anemia due to suppressed erythropoiesis during inflammation.

❑ C-reactive protein is positive (especially during acute phase).

❑ Cardiac enzyme levels may be increased in severe carditis.

❑ Antistreptolysin-O titer is elevated in 95% of patients within 2 months of onset.

❑ Electrocardiogram changes aren’t diagnostic; but PR interval is prolonged in 20% of patients.

❑ Chest X-rays show normal heart size (except with myocarditis, heart failure, or pericardial effusion).

❑ Echocardiography helps evaluate valvular damage, chamber size, and ventricular function.

❑ Cardiac catheterization evaluates valvular damage and left ventricular function in severe cardiac dysfunction.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Rocky Mountain spotted fever: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

CONFIRMING DIAGNOSIS Diagnosis is usually based on a history of tick bite or travel to a tick-infested area and a positive complement fixation test (which shows a fourfold increase in convalescent antibody titer compared with acute titers). Blood cultures or skin biopsy at the rash site should be performed to isolate the organism and confirm the diagnosis.

Another common but less reliable antibody test is the Weil-Felix reaction, which also shows a fourfold increase between the acute and convalescent sera titer levels. Increased titers usually develop after 10 to 14 days and persist for several months.

Additional recommended laboratory tests consist of a platelet count for thrombocytopenia (12,000 to 150,000/µl) and a white blood cell count (elevated to 11,000 to 33,000/µl) during the second week of illness.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Purpura: History and physical examination
(Professional Guide to Signs & Symptoms (Fifth Edition))

Ask the patient when he first noticed the lesion and whether he has noticed other lesions on his body. Does he or his family have a history of a bleeding disorder or easy bruising? Find out what medications he’s taking, if any, and ask him to describe his diet. Ask about recent trauma or transfusions and the development of associated signs, such as epistaxis, bleeding gums, hematuria, and hematochezia. Ask about systemic complaints that may suggest infection, such as fever. If the patient is female, ask about heavy menstrual flow.

Inspect the patient’s entire skin surface to determine the type, size, location, distribution, and severity of purpuric lesions. Inspect the mucous membranes. Remember that the same mechanisms that cause purpura can also cause internal hemorrhage, although purpura isn’t a cardinal indicator of this condition.

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Source: Professional Guide to Signs & Symptoms (Fifth Edition), 2006

Fever [Pyrexia]: History and physical examination
(Professional Guide to Signs & Symptoms (Fifth Edition))

If the patient’s fever is only mild to moderate, ask him when it began and how high his temperature reached. Did the fever disappear, only to reappear later? Did he experience any other symptoms, such as chills, fatigue, or pain?

Obtain a complete medical history, noting especially immunosuppressive treatments or disorders, infection, trauma, surgery, diagnostic testing, and use of anesthesia or other medications. Ask about recent travel because certain diseases are endemic.

Let the history findings direct your physical examination. (See Differential diagnosis: Fever, pages 338 and 339.) Because fever can accompany diverse disorders, the examination may range from a brief evaluation of one body system to a comprehensive review of all systems. (See How fever develops, page 340.)

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Source: Professional Guide to Signs & Symptoms (Fifth Edition), 2006

Fever: History
(The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter)

A. Taking a detailed patient history is critical; include questions relating to travel, animal exposure, occupation, injuries or operations, household members or contacts who are ill, medications, past illnesses, and a complete review of systems.

B. Chills, malaise, myalgia, headache, and fever are common with infectious diseases.

C. The febrile pattern may be helpful in making a diagnosis. Antipyretics, antibiotics, and glucocorticoids affect the fever pattern. Specific patterns of fever are shown in Table 2.4.

Physical examination

A. The examination should include the skin, lymph nodes, eyes, nail beds, heart, lungs, abdomen, joints, nervous system, and genitourinary system, including rectal and bimanual pelvic examinations.

B. Infections will increase the pulse rate approximately 10 beats per minute for each 0.5°C (1.0°F) temperature increase.

C. When fever is present, the respiratory rate will frequently increase above the usual 12 to 14 breaths per minute.

D. Infections with Mycoplasma pneumonia, psittacosis, and typhoid fever are often associated with a relative bradycardia.

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Source: The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter, 2000

Rash Accompanied by Fever: History
(The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter)

History is quite important and should include standard items, such as onset, duration, aggravating factors, relieving factors, and associated symptoms. Additionally, other factors to consider, include:

A. Exposure history. Are any other family members or close contacts ill? Is there a history of exposure to brackish water, mosquitoes, foreign travel, and so forth?

B. Are there any underlying illnesses or a significant possibility of immunologic compromise (e.g., undiagnosed HIV infection)?

Physical examination

A. Examine the lesions and their distribution carefully. Classify the rash as petechial, maculopapular, vesiculobullous, erythematous, or urticarial. Note the distribution of the rash. For instance, rubella and rubeola generally begin on the face and spread to the trunk, whereas RMSF petechiae tend to occur on the ankles and wrists first.

B. Conduct a general physical examination. Areas of particular concern are:

1. Head, eyes, ears, nose, and throat. The presence of Koplik’s spots is pathognomic for rubeola. The discovery of a tick lends support to the diagnosis of RMSF. Sinusitis may represent a source for meningococcemia. Pharyngitis in a young adult with diffuse erythema may be caused by C. haemolyticum. Mucous membrane swelling may indicate early anaphylaxis.

2. Lung examination. Expiratory wheezing, especially in a patient who has recently received medications or contrast dye, can indicate anaphylaxis. Evidence of pneumonia is consistent with psittacosis and mycoplasma.

3. Cardiac examination. Cardiovascular collapse is associated with meningococcemia and other sepsis. A new murmur (Chapters 7.6 and 7.7) may indicate subacute bacterial endocarditis in a patient with subungual or scleral petechiae.

4. Genital examination. Purulent urethral drainage or evidence of pelvic inflammatory disease supports consideration of gonorrhea. A chancre would support a diagnosis of syphilis, although palmar lesions often occur well after healing of the initial chancre.

5. Joint examination and extremities. A petechial rash near the ankles and wrists is suggestive of RMSF. Evidence of joint swelling supports a diagnosis of meningococcemia or gonococcemia. A maculopapular rash may be seen in juvenile rheumatoid arthritis and other rheumatologic conditions as well.

6. Neurologic examination. Evidence of meningitis supports a diagnosis of meningococcemia. Patients with RMSF may also have meningeal signs.

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Source: The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter, 2000

Petechiae and Purpura: History
(The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter)

A. Have there been any recent illnesses? Henoch-Schönlein purpura is associated with a preceding upper respiratory infection in 60% to 75% of cases (1). Streptococcus pneumoniae is the most commonly cited organism. Various other infections may be responsible for thrombocytopenias and vasculitis.

B. Has there been any recent medication usage? Quinidine, quinine, sulfa, aspirin, and many other medications have been associated with purpuric lesions.

C. Are there any additional symptoms, such as abdominal or joint pain, or gastrointestinal symptoms including changes in stool characteristics? Henoch-Schönlein purpura is associated with all of these; abdominal pain is noted in 40% to 80% of patients (1).

D. Is there a history of heavy menses or mucous membrane bleeding? Coagulation abnormalities such as von Willebrand’s disease (present in 0.5% to 1% of the population) or platelet abnormalities are most likely (3) (Chapter 11.5).

E. Is there a history of prior transfusions or heavy bleeding with previous operations?

F. Are there risk factors for a history of liver disease? There may be impaired synthesis of coagulation factors.

G. Has there been a similar rash in the past? A long history of purpura may be present in idiopathic thrombocytopenic purpura (ITP) as it tends to be a chronic course with an insidious onset in adults.

H. If the patient is a newborn, was there maternal illness, drug exposure, maternal ITP, or was vitamin K given? Hemorrhagic disease of the newborn develops on the second or third day of life. The most common causes of purpura fulminans in the neonatal period are congenital deficiencies of proteins C and S (1).

Physical examination

A. General and vital signs. Does the patient appear toxic or unstable? Considerations would include meningococcemia, Rocky Mountain spotted fever, disseminated intravascular coagulation (DIC), sepsis from Staphylococcus aureus, or thrombotic thrombocytopenic purpura.

B. Skin. Purpura should not blanch or only partially blanch with pressure. Petechiae are generally indicative of a quantitative or qualitative platelet abnormality. These nonpalpable petechiae may be caused by thrombocytopenia, which is either congenital or acquired (Chapter 16.7). The acquired thrombocytopenia can be caused by decreased platelet production as seen with viral infections, B₁₂ or folate deficiency, iron deficiency, or a drug reaction. It is also seen with evidence of platelet destruction as present in ITP, connective tissue disease, leukemia, drugs, DIC, and thrombotic thrombocytopenic purpura. Abnormal platelet function is seen with aspirin ingestion, kidney and liver dysfunction, and in the thrombocytosis seen with myeloproliferative disorders. Significant straining with the Valsalva maneuver can cause petechiae. Lastly, the chronic pigmented purpura are the brown-orange spots occasionally seen on the lower extremities of adults. Schamberg’s disease is the most frequently seen and well known of the group. In these disorders, petechia are often intermixed with the pigmentation.

Ecchymoses are usually associated with coagulation disorders (e.g., in hemophilia, von Willebrand’s disease, anticoagulant usage, DIC, and vitamin K deficiency). Also responsible for ecchymoses are weakened connective tissue with less protection for vessels, as seen in senile purpura; glucocorticoid excess; vitamin C deficiency; and congenital disorders, such as Ehlers–Danlos syndrome.

Palpable purpura are usually secondary to a vasculitis. The causes are many and include hypersensitivity vasculitis to drugs; infections, including viral, rickettsial, and bacterial illnesses; cryoglobulinemias, such as Waldenström’s; and granulomatous causes, such as Wegener’s granulomatosis.

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Source: The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter, 2000

Purpura/Petechiae/Excessive Bleeding: Differential Overview
(Field Guide to Bedside Diagnosis)

Purpura

❑Trauma

❑Senile purpura

❑Drugs

❑Vasculitis

❑Vitamin K deficiency

❑Psychogenic purpura

❑Cholesterol emboli

❑Warfarin necrosis

❑Scurvy

❑Thrombotic thrombocytopenic purpura

❑Henoch-Schonlein purpura

❑Amyloidosis

Petechiae

❑Autoimmune thrombocytopenia

❑Bacteremia

❑Hypersplenism

Excessive Bleeding

❑Over-anticoagulation

❑Thrombocytopenia

❑von Willebrand disease

❑Circulating anticoagulant

❑Disseminated intravascular coagulation

❑Hemophilia

Diagnostic Approach

A patient with a suspected bleeding disorder should be questioned about response to trauma, past bleeding problems, for example with surgery or dental extractions, history of transfusion, menstrual history and dietary habits. Absence of abnormal bleeding with surgery, significant trauma, or dental extractions makes an inherited bleeding disorder unlikely.

Petechiae are small capillary hemorrhages resulting from platelet or vascular abnormalities. Petechiae on the lower extremities or mucous membranes are usually caused by thrombocytopenia. Tender, elevated petechiae plus abnormalities in other organs suggests vasculitis. Platelet defect disorders produce petechiae and ecchymoses occurring immediately after local trauma. Bleeding is superficial, occurring in the skin, the mucous membranes, the nose, and the gastrointestinal and genitourinary tracts. Bleeding does not occur with normal platelets until the count falls to less than 50,000, and the threshold for important bleeding is 20,000. Oozing blood around catheters suggests DIC, vitamin K deficiency, or platelet abnormalities.

Large-area bruising occurs with vitamin-K–dependent factor deficiency, but not with hemophilia. Plasma protein disorders produce bleeding in deep tissues, such as joints, muscle, and retroperitoneum. The onset of such bleeding can be delayed for hours after trauma.

Palpable purpura is seen with autoimmune or infectious (e.g., meningococcemia, endocarditis) vasculitis. Infectious emboli have an irregular outline, whereas lesions of leukocytoclastic vasculitis are circular.

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Source: Field Guide to Bedside Diagnosis, 2007

Fever of Unknown Origin: Differential Overview
(Field Guide to Bedside Diagnosis)

Infection

❑ HIV

❑ Tuberculosis

❑ Endocarditis

❑ Osteomyelitis

❑ Malaria

❑ Syphilis

❑ Zoonosis

❑ Typhoid fever

❑ Chronic meningococcemia

Neoplasm

❑ Lymphoma

❑ Liver metastases

❑ Renal cell carcinoma

❑ Atrial myxoma

Collagen-Vascular Disease

❑ Giant cell arteritis

❑ Systemic lupus erythematosus

❑ Vasculitis

❑ Rheumatic fever

❑ Still disease

Other

❑ Drugs

❑ Heat stroke

❑ Factitious

❑ Malignant hyperthermia

❑ Multiple pulmonary emboli

Diagnostic Approach

Fever of unknown origin (FUO), 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%). It is most commonly caused by an atypical presentation of a common disease. Always document the fever before pursuing the evaluation.

Consider relatively hidden (deep) sites: retroperitoneum (hematoma or infection), bone, dental, sinus, ovary, prostate, subphrenic (following abdominal surgery), renal, spleen, or prostheses. With FUO in a hospitalized patient, consider sequestered sites (e.g., sinuses in intubated patients or implanted hardware), indwelling lines, C. difficile, or drug reactions. With FUO in a neutropenic patient, consider catheters, perianal infections, Candida, and Aspergillus. Cardinal signs may be absent, e.g., meningitis with opportunistic pathogens without meningismus in 63%, and pneumonia without purulent sputum in 92%. Neutropenic fevers are usually due to bacteremia, with fungal organisms becoming predominant after 7 days of unremitting fever. Fever may also be due to the underlying neoplasm, drugs such as antibiotics, or blood products.

Examine for subtle clues:

• Petechial eruptions in meningococcemia and Rocky Mountain Spotted Fever

• Pustular lesions in gonococcemia or staphylococcal sepsis

• Ecthyma gangrenosum in Pseudomonas sepsis

• Splinter hemorrhages, conjunctival hemorrhages, Roth spots, Osler nodes, and Janeway lesions in endocarditis

• Choroidal tubercles in miliary tuberculosis and candidemia

• Splenomegaly in endocarditis, lymphoma, and cirrhosis

• Hepatic bruit or friction rub in subphrenic abscess

• Temporal artery or scalp tenderness or jaw claudication in giant cell arteritis

• Epitrochlear lymphadenopathy in syphilis

Extreme elevations of fever (.40°C) are found in heat stroke, hypothalamic dysfunction, meningitis, midbrain hemorrhage, falciparum malaria, Rocky Mountain Spotted Fever, typhus, sepsis, malignant hyperthermia, and hypernephroma.

Relative bradycardia occurs in salmonellosis (typhoid fever), meningitis with increased intracranial pressure, mycoplasma and legionella pneumonia, factitious fever, tularemia, brucellosis, mumps, hepatitis, and with concomitant beta blockers. Bradycardia in fever may also signal cardiac conduction abnormalities in acute rheumatic fever, Lyme disease, viral myocarditis, or endocarditis with valve ring abscess.

Relapsing fevers (days of fever alternating with days without) occur in brucellosis (fever with physical activity), Hodgkin disease, extrapulmonary tuberculosis, malaria, and Lyme disease. Hectic fever (difference between peak and trough .1.5°C) suggests abscess, pyelonephritis, ascending cholangitis, tuberculosis, lymphoma, and drug reactions. Absence of diurnal variation suggests a central source. Reversal of the diurnal pattern (“typhus inversus”) occurs with disseminated tuberculosis, typhoid fever, polyarteritis nodosa, and salicylate toxicity.

FUO in patients from the developing world include tuberculosis, typhoid, amebic liver abscesses, AIDS, and geographically restricted infections such as malaria, schistosomiasis, brucellosis, kala azar, filariasis, or Lassa fever. They may present after long incubation or latency periods.

When FUO lasts longer than 6 months, consider factitious fever, granulomatous hepatitis, neoplasm, Still disease, infection, collagen-vascular disease, or exaggerated circadian rhythm.

Patients who remain undiagnosed have a good prognosis (83% resolution in 1 year, 4% mortality).

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Source: Field Guide to Bedside Diagnosis, 2007

Allergic purpura: Diagnosis
(Handbook of Diseases)

No laboratory test result clearly identifies allergic purpura (although the white blood cell count and erythrocyte sedimentation rate are elevated). Diagnosis therefore requires careful observation, usually during the second or third attack. Except for a positive tourniquet test result, coagulation and platelet function test results are usually negative. X-rays of the small bowel may reveal areas of transient edema; test results for blood in the urine and stool are often positive. Increased blood urea nitrogen and serum creatinine levels may indicate renal involvement. The diagnosis must rule out other forms of nonthrombocytopenic purpura.

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Source: Handbook of Diseases, 2003

Idiopathic thrombocytopenic purpura: Diagnosis
(Handbook of Diseases)

Platelet count less than 20,000/µl combined with prolonged bleeding time suggest ITP. Platelet size and morphologic appearance may be abnormal; anemia may be present if bleeding has occurred.

As in thrombocytopenia, bone marrow studies show an abundance of megakaryocytes and a shortened circulating platelet survival time (hours or days). Occasionally, platelet antibodies may be found in vitro, but this diagnosis is usually inferred from platelet survival data and the absence of an underlying disease. The patient’s immunoglobulin G level may also be increased.

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Source: Handbook of Diseases, 2003

Rheumatic fever and rheumatic heart disease: Diagnosis
(Handbook of Diseases)

Recognition of one or more classic signs or symptoms (carditis, polyarthritis, chorea, erythema marginatum, or subcutaneous nodules) and a detailed patient history allow diagnosis. The following laboratory data support the diagnosis:

❑ White blood cell count and erythrocyte sedimentation rate may be elevated (during the acute phase); blood studies show slight anemia from suppressed erythropoiesis during inflammation.

❑ C-reactive protein is positive (especially during the acute phase).

❑ Cardiac enzyme levels may be increased in those with severe carditis.

❑ Antistreptolysin O titer is elevated in 95% of patients within 2 months of onset. (Rising antiDNase B test results can also detect recurrent streptococcal infection.)

❑ Electrocardiography changes aren’t diagnostic, but the PR interval is prolonged in 20% of patients.

❑ Chest X-rays show normal heart size (except with myocarditis, heart failure, or pericardial effusion).

❑ Echocardiography helps evaluate valvular damage, chamber size, and ventricular function.

❑ Cardiac catheterization evaluates valvular damage and left ventricular function in those with severe cardiac dysfunction.

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Source: Handbook of Diseases, 2003

Fever: History
(Alarming Signs and Symptoms: Lippincott Manual of Nursing Practice Series)

If the patient’s fever is mild to moderate, ask him when it began and how high his temperature reached. Did the fever disappear, only to reappear later? Did he experience any other symptoms, such as chills, fatigue, or pain?

Obtain a complete medical history, noting immunosuppressive treatments or disorders, infection, trauma, surgery, diagnostic testing, and use of anesthesia or other medications. Ask about recent travel because certain diseases are endemic.

Physical examination

Let the history findings direct your physical examination. Because fever can accompany diverse disorders, the examination may range from a brief evaluation of one body system to a comprehensive review of all systems. (See How fever develops, pages 148.) Assess vital signs and evaluate the patient for complications related to the fever such as dehydration, body aches, fatigue, anorexia, and seizure activity.

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Source: Alarming Signs and Symptoms: Lippincott Manual of Nursing Practice Series, 2007

Fever: History
(Signs & Symptoms: A 2-in-1 Reference for Nurses)

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Source: Signs & Symptoms: A 2-in-1 Reference for Nurses, 2007

Purpura: History
(Signs & Symptoms: A 2-in-1 Reference for Nurses)

Ask the patient when he first noticed the lesion and whether he has noticed other lesions on his body. Does he or his family have a history of a bleeding disorder or easy bruising? Find out what medications he’s taking, if any, and ask him to describe his diet. Ask about recent trauma or transfusions and the development of associated signs, such as epistaxis, bleeding gums, hematuria, and hematochezia. Also ask about systemic complaints that may suggest infection, such as fever. If the patient is female, ask about heavy menstrual flow.

CULTURAL CUE:Make sure to ask your patient if he uses any type of folk medicine. Coin rubbing, practiced by cultures such as the Vietnamese, may produce ecchymoses on the back and abdomen; these marks may be misdiagnosed as abuse.

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Source: Signs & Symptoms: A 2-in-1 Reference for Nurses, 2007

Fever: Clinical Features and Diagnosis: Acute Fever
(The Diagnostic Approach to Symptoms and Signs in Pediatrics)

Common Causes

Infectious

Infectious causes of acute fever are listedbelow and discussed in other chapters.

Respiratorytract

Upperrespiratory tract infection (common cold)

Pharyngitis

Tonsillitis

Otitis media

Herpes gingivostomatitis

Herpangina

Sinusitis

Croup

Bronchiolitis

Bronchitis

Pneumonia (viral, bacterial, mycoplasma)

Pertussis

Gastrointestinal

Gastroenteritis

Appendicitis

Hepatitis

Genitourinary

Urinary tract infection (includingpyelonephritis)

Sexually transmitted diseases

Musculoskeletal

Septic arthritis

Osteomyelitis

Myositis

Central nervous system

Meningitis(viral, bacterial)

Viral encephalitis

Infections associated with prominentrash

Roseola

Hand-foot-mouth syndrome

Varicella

Erythema infectiosum (parvovirus B19)

Measles

Scarlet fever

Meningococcemia

Rocky Mountain spotted fever

Other

Viral illnesses

Septicemia/bacteremia

Infectious mononucleosis

Lymphadenitis

Cellulitis/abscess

Cat scratch disease

Dental abscess

Periorbital cellulites

Parotitis

Noninfectious

Drug Reactions

Hypersensitivityreactions are responsible for most cases of drug fever.

Although fever can occur without otherfindings, urticarial rash and peripheral eosinophilia make diagnosismore likely.

Vaccine Reactions

Reactionsto acellular pertussis vaccine can produce fever but are uncommon.

Within 7–10 days after administrationof live measles vaccine or measles, mumps, rubella (MMR) vaccine,fever can occur and is often associated with macular or papular rash.

Trauma

Crush injuries and fractures of large bonescan cause fever due to large amount of tissue damage and releaseof inflammatory mediators.

Burns

Fever may occur with severe burns, even inabsence of infection, because of fluid losses and resetting of thermoregulatorycenter. Severe sunburn also may cause fever.

Kawasaki Disease

Definedas vasculitis of unknown cause that usually occurs in children <5yrs of age.

Diagnostic criteria are absence ofany other disease process and presence of fever for ≥5 days associatedwith 4 of 5 signs:

Bilateral conjunctival injection

Cervical lymphadenopathy

Macular or papular rash primarily ontrunk

Mucous membrane involvement with dry,fissured lips, strawberry tongue, or pharyngeal injection

≥1 change in extremities, includingpalmar erythema, edema, and periungal or generalized desquamation

Lab findings include leukocytosis,pyuria, proteinuria, spinal fluid pleocytosis, elevation in serumaminotransferases, and increased erythrocyte sedimentation rate.

Chest radiograph may show small pleuraleffusions.

Platelet count may be normal at onset,but thrombocytosis usually occurs during second week of illness.

Complications include coronary arteryaneurysms, myocarditis, and myocardial infarction.

2-D echocardiography may reveal coronaryartery aneurysms within 1–2 cm of origin of coronary arteriesfrom aorta.

Uncommon Causes

Infectious

Many infections in this category, as listedbelow, are discussed in other chapters.

Respiratorytract

Viral(hantavirus pulmonary syndrome)

Bacterial [supraglottitis,bacterial tracheitis, abscess (peritonsillar, retropharyngeal, lateral pharyngeal),tuberculosis, actinomycosis, nocardiasis, Legionella]

Fungal (aspergillosis, blastomycosis,histoplasmosis, coccidioidomycosis)

Parasitic (P. carinii)

Gastrointestinal

Amebiasis

Pancreatitis

Cholecystitis

Cholangitis

Peritonitis

Intraabdominal abscess

Genitourinary

Epididymitis

Orchitis

Abscesses (perinephric, tuboovarian)

Cardiac

Acute rheumatic fever

Myocarditis

Pericarditis

Endocarditis

Central nervous system (brain abscess)

Other

Viral (HIV, rabies)

Bacterial [staphylococcalscalded skin syndrome, toxic shock syndrome, orbital cellulitis/abscess,Borrelia (relapsing fever), brucellosis, leptospirosis, plague,psittacosis (ornithosis), rat-bite fever, syphilis, tularemia, tetanus]

Fungal (disseminated histoplasmosis,nonpulmonary blastomycosis)

Parasitic [malaria, ascariasis,toxocariasis (visceral larva migrans, ocular larva migrans), toxoplasmosis,trichinosis]

Rickettsial [endemic typhus(murine), epidemic typhus (louse-borne typhus), Q fever, rickettsialpox, ehrlichiosis]

Hantavirus Pulmonary Syndrome

Can occurafter exposure to infected rodents (most commonly, deer mouse),their saliva, or excreta.

Characterized by acute onset of fever,headache, myalgia, cough, vomiting, and diarrhea followed by developmentof hypotension and noncardiogenic pulmonary edema. Leukocytosiswith immature granulocytes, thrombocytopenia, and elevated Hct arefrequent findings.

Reverse-transcriptase polymerase chainreaction or enzyme immunoassay can detect viral antigen from clinicalsamples. Diagnosis also can be confirmed serologically.

Borrelia (Relapsing Fever)

Caused byspirochetes of Borrelia. Infected ticks (Ornithodoros species) andlice (P. humanus) are sources of human infections. Most cases inU.S. are transmitted by ticks, which become infected by feedingon rodents and other small mammals.

Incubation period of 7–10days is followed by fever, headache, chills, myalgia, and arthralgia,which may last up to 1 wk. Transient macular rash, petechiae ofskin, jaundice, and hepatosplenomegaly may occur.

Complications include pneumonia, myocarditis,and meningitis. After 5- to 10-day interval, relapse occurs withfever and same clinical findings as described above.

Spirochetes can be seen by dark-fieldmicroscopy and in Wright-stained smears of peripheral blood. Positiveblood culture is also diagnostic.

Brucellosis

Transmittedby direct contact with infected animals (goats, sheep, cows, swine)or by ingestion of contaminated milk or milk products produced bythem.

Onset can be acute or insidious, withfever, headache, abdominal pain, arthralgia, myalgia, weight loss,lymphadenopathy (especially cervical and axillary), and hepatosplenomegaly.Prolonged fever without any other findings sometimes occurs.

Complications include meningitis, osteomyelitis,and endocarditis.

Organism can sometimes be culturedfrom blood, urine, spinal fluid, bone marrow, or lymph node. Ifthese cultures are negative, diagnosis depends on serologic findings.Serum agglutination test with antibody titer ≥1:160 or 4-foldincrease in agglutination titer on serial samples is diagnostic.

Leptospirosis

L. interrogansinfects humans through contact with animal urine in contaminated foodor water. Incubation period is 2–20 days.

Acute illness usually consists of fever,headache, chills, malaise, myalgia, vomiting, lymphadenopathy, andabdominal pain. Hepatic (hepatomegaly, jaundice, liver failure),renal (azotemia, renal failure), and CNS dysfunction (aseptic meningitis,alteration in consciousness) may follow.

Diagnosis confirmed by positive blood,urine, or spinal fluid cultures; 4-fold increase in serial agglutinationtiters; or visualization of spirochete by dark-field microscopyof urine.

Plague

Y. pestisis responsible for plague. Most common form is bubonic plague, whichis usually transmitted by bites of infected fleas and uncommonlyby contact with infected tissues and fluids of wild rodents (e.g.,prairie dogs, ground squirrels, chipmunks, hares, rabbits, and rats).

Characterized by fever and painfulregional adenopathy, usually involving cervical, inguinal, or axillarylymph nodes (buboes).

Less common forms include pneumonicplague (cough, fever, dyspnea, hemoptysis), septicemic plague (fever,hypotension, coagulopathy), and meningeal plague (fever, headache,photophobia, seizures).

Positive fluorescent antibody testof sputum, lymph node aspirate, blood, or spinal fluid is presumptiveevidence of infection. Serologic tests also may confirm diagnosis.Positive sputum, lymph node, blood, or spinal fluid cultures aredefinitive.

Psittacosis (Ornithosis)

C. psittacicauses psittacosis, which is transmitted from parrots and otherrelated species (parakeets, finches, cockatoos), and ornithosis,which is acquired from turkeys, pigeons, ducks, chickens, and otherfowl. Transmission is by inhalation of organisms from infected bird'senvironment. Incubation period is usually 1–2 wks.

Affected individuals have acute respiratorytract infection with fever and nonproductive cough.

Chest radiograph usually shows interstitialpneumonia. Usual method of diagnosis is serologic, with 4-fold increasein complement fixation antibody titer. With compatible clinicalpicture, single complement fixation titer ≥1:32 is also considereddiagnostic.

Rat-Bite Fever

May followrodent bite, usually that of rat.

2 different organisms, S. moniliformis,which is more common in U.S., and S. minus, which is more commonin Japan, can cause this infection.

Clinical features include fever, chills,headache, muscle pain, and rash (macular, papular, or petechial).

Migratory polyarthritis/arthralgiasoccur in some cases of S. moniliformis infection. Complicationsinclude pneumonia, meningitis, myocarditis, pericarditis, endocarditis,and soft tissue or solid organ abscesses. Positive culture fromsite of bite, blood, or joint fluid confirms diagnosis.

With S. minus infection, the bite maybe followed by ulceration, lymphadenopathy, and rash composed ofpurple or red plaques. Diagnosis of S. minus may be confirmed byobservation of organisms by dark-field microscopy in wet mountsof blood, exudate of lesion, and lymph nodes.

Syphilis

T. pallidumcauses syphilis, which may be congenital or acquired. See Chap. 36, Jaundice, fordiscussion of congenital syphilis.

Acquired syphilis almost always occursby sexual transmission.

Incubation period is 10–90days.

In primary stage, ≥1 painless ulcer(chancres) occurs on skin or mucous membranes at site of inoculation,usually on genitalia.

During secondary stage, which occurs1–2 mos later, generalized macular or papular rash appears,usually involving palms and soles. Fever, malaise, headache, arthralgia,generalized adenopathy, splenomegaly, and condyloma lata also canoccur.

Tertiary stage occurs several yearsto decades later and is characterized by aortitis or gummatous changesof skin, bones, or viscera.

Neurosyphilis can occur at any stage.

Nontreponemal reagin antibody test(rapid plasma reagin card test) and VDRL slide test, which measureimmunoglobulins directed against cardiolipin antigen, are usefulscreening tests.

Any positive test result should beconfirmed by 1 treponemal test.

Specific treponemal antibody serologictests include fluorescent treponemal antibody absorption test (FTA-ABS),which usually remains positive for life, even with successful therapy.

Microscopic dark-field exam of lesionscraping or lymph node aspirate that shows spirochetes or positivedirect fluorescent antibody test of lesion exudate or tissue isalso diagnostic.

Diagnosis of CNS involvement is establishedby positive CSF VDRL or FTA-ABS tests. CSF pleocytosis and increasedCSF protein concentration also may be found.

Tularemia

Source ofinfection with F. tularensis is infected animal or carcass, usuallyrabbit. Infection is acquired by ingestion of contaminated meator water, handling infected animals, or bites by dog ticks or deerflies that have come into contact with infected animal.

Fever, chills, headache, and myalgiaare usual findings. Common presentation is ulceroglandular syndromewith painful, swollen, ulcerating papule and inflamed lymph nodesthat may drain spontaneously.

Other syndromes are glandular (absenceof skin or mucous membrane involvement); oculoglandular (conjunctivitisand preauricular lymph node involvement); oropharyngeal (exudativepharyngitis); typhoidal (fever and hepatosplenomegaly); and pneumonic(cough).

Positive culture or 4-fold increasein serum agglutinin titer is diagnostic.

Malaria

Sporozoaof genus Plasmodium cause malaria, which occurs in many tropicaland subtropical countries. Bite by infected female Anopheles mosquitotransmits infection. 4 known types of malaria are caused by differentspecies and have the following incubation periods:

P. falciparum,9–14 days

P. vivax, 12–17 days

P. ovale, 16–18 days

P. malariae, 18–40 days

P. falciparum and P. vivax infectionsare most common, whereas P. falciparum infection is most serious.Mixed infections with more than 1 type also occur.

Typical symptoms are fever with chills,sweats, and headache. Fever usually occurs every other day withP. vivax, P. falciparum, and P. ovale infections, and every thirdday with P. malariae infection. Vomiting, diarrhea, cough, and abdominalpain are other manifestations. Significant hemolysis produces pallorand jaundice. Hepatosplenomegaly may occur with chronic infection.

Clinical syndromes that may occur withP. falciparum infection include

Febrile illness without specific or localizingsigns

Severe anemia

Respiratory failure ± pulmonaryedema

Renal failure secondary to acute tubularnecrosis

Cerebral malaria with seizures andalteration of consciousness

Vascular collapse and shock associatedwith adrenal insufficiency

P. vivax and P. ovale may cause anemiaand hypersplenism, whereas nephrotic syndrome may be associatedwith P. malariae infection. Any type can cause congenital malaria,which is characterized by fever, irritability, and lethargy.

Analysis of thick and thin blood smearsusing Wright or Giemsa stain identifies parasite and confirms diagnosis.

Ascariasis

Infectionwith roundworm A. lumbricoides is usually asymptomatic, but diarrhea, vomiting,and abdominal pain sometimes occur. Larval migration through lungcan cause transient pneumonitis associated with fever and eosinophilia.

Adult worms, which are whitish brownin color and 15–30 cm (males) or 20–40 cm (females)long, sometimes pass through rectum.

Identification of ova by microscopicidentification of stool or adult worm is diagnostic.

Toxocariasis (Visceral Larva Migrans, Ocular Larva Migrans)

Dog roundwormT. canis and cat roundworm T. cati cause toxocariasis.

Ingestion of infective eggs from soilcauses human infection, which is most common in toddlers.

Although infection can be asymptomatic,with eosinophilia as its only manifestation, other findings includefever, cough, macular or papular rash, and hepatosplenomegaly. Pneumonia,myocarditis, and encephalitis are rare complications. Ocular invasionusually occurs without other evidence of infection.

Enzyme immunoassay for serum Toxocaraantibodies available through CDC is both sensitive and specificfor visceral larva migrans and less sensitive for ocular larva migrans.Liver biopsy also may detect larvae, but yield is low.

Trichinosis

Infectionwith nematode T. spiralis is acquired by eating undercooked meat(usually pork) containing encysted larvae.

Fever, diarrhea, vomiting, and abdominalpain follow in 1–7 days. During next 2–8 wks,fever, myalgia, urticarial rash, and hemorrhages (conjunctival andsubungual) may develop. Eosinophilia as high as 70% alsomay occur. Most serious complication is myocarditis.

Identification of larvae in suspectmeat is fastest way to diagnose. Diagnosis also can be made by visualizinglarvae in muscle biopsy or by increase in paired acute and convalescentantibody titers.

Endemic Typhus (Murine)

Murine typhuscaused by R. mooseri is primarily infection of rats. Transmissionto humans occurs by bite of infected rat or inhalation of infectedrat excreta 1–2 wks after exposure. Infection occurs insoutheastern U.S. and is more common during summer months.

Fever, headache, and myalgia are usualfindings. Macular or papular rash occurs about 1 wk into illness,which lasts 2–3 wks.

Diagnosis is usually confirmed by serologictests.

Epidemic Typhus (Louse-Borne Typhus)

Humans areonly known reservoir of R. prowsekii, which causes epidemic typhus.

Infection is transmitted by infectedbody louse feces, usually through skin abrasion. Crowding, poorpersonal hygiene, and poverty are factors that contribute to itsoccurrence.

Usual incubation period is 1–2wks.

Begins with sudden onset of fever,chills, headache, and myalgia. Macular or papular rash appears in3–7 days and is followed by petechial or hemorrhagic rash.Face, palms, and soles are usually spared. In severe cases pneumonia,renal failure, and alteration in consciousness may occur.

Diagnosis may be confirmed by isolationof organism, visualization of rickettsiae in tissues, detectingrickettsiae by polymerase chain reaction, or by serologic testing.

Q Fever

Caused byC. burnetii, which infects cattle, sheep, goats, and rodents.

Human infection follows inhalationof infected dust from exposure to hides or products of conceptionof these animals.

Incubation period is 10–20days.

Acute onset of fever, chills, headache,and weakness are characteristic. Hepatosplenomegaly and weight lossoften occur. Persistent cough may signify pneumonia. High, spikingfever may continue for 1–3 wks, with gradual resolution.Major manifestations of chronic disease are hepatitis and endocarditis.

Immunofluorescence, complement fixation,enzyme immunoassay, and immune adherence hemagglutination antibodytests are used diagnostically.

Rickettsial Pox

Definedas mild illness caused by R. akari.

House mice harbor this organism, whichis transmitted to humans by mites.

Incubation period is 2–7 daysfollowing attachment of infected mite.

Mite bite produces red papule, whichforms vesicle that ulcerates. Fever, headache, chills, sweats, myalgia,and papular/vesicular eruption follow in 1–3 days.

During acute stage, organism may beisolated from blood. Serologic tests are also diagnostic.

Ehrlichiosis

Consistsof at least 2 distinct diseases: human monocytic ehrlichiosis causedby E. chaffeensis and human granulocytic ehrlichiosis caused byan unnamed Ehrlichia species. Both are transmitted by tick vectors.

Both resemble Rocky Mountain spottedfever, with fever, headache, malaise, chills, and myalgia. Macularor papular rash that occasionally can be petechial occurs commonlywith monocytic form and rarely with granulocytic form.

Lab findings include anemia, thrombocytopenia,increased liver aminotransferases, and CSF pleocytosis with predominanceof lymphocytes.

Diagnosis may be confirmed by serologicmethods or by polymerase chain reaction of DNA from a clinical sample.

Noninfectious

Many uncommon noninfectious causes, as listedbelow, are discussed in other chapters.

Respiratory

Pulmonaryinfarction

Pulmonary embolism

Gastrointestinal

Intestinal obstruction

Inflammatory bowel disease

Cardiac (postpericardiotomy syndrome)

Hematologic

Intravascular hemolysis

Bleeding into closed space

Endocrine

Thyrotoxicosis

Diabetes insipidus

Central nervous system

Intracranialinjury and hemorrhage

Spinal cord injury

Hypothalamic and brain stem lesions

Status epilepticus

Neoplasia

Leukemia

Lymphoma

Neuroblastoma

Pheochromocytoma

Connective tissue disorders

Juvenile rheumatoidarthritis

Systemic lupus erythematosus

Polyarteritis nodosa

Polymyositis

Dermatomyositis

Mixed connective tissue disease

Poisonings

Atropine

Cocaine

Salicylate

Lysergic acid diethylamide

Hydrocarbons

Organophosphates

Tricyclic antidepressants

Amphetamines

Phenothiazines

Other

Spider bites (black widow, brown recluse)

Stevens-Johnson syndrome

Heat-related illness

Serum sickness

Anhidrotic ectodermal dysplasia

Familial dysautonomia

Sarcoidosis

Familial Mediterranean fever

Factitious fever

Central Nervous System

Increasedtemperature may occur with intraventricular hemorrhage as well assubdural hematoma or effusion. CT is diagnostic.

Absence of effective control mechanismsof temperature regulation sometimes results from spinal cord injury.In such cases, significant increase in environmental temperatureproduces hyperpyrexia.

Any hypothalamic or brainstem lesionmay damage hypothalamic temperature-regulating center and producehyperpyrexia. Hypoxic-ischemic encephalopathy and brain tumors arecommon examples.

Prolonged status epilepticus may resultin autonomic changes with associated increase in temperature.

Neoplasia

Fever in children with cancer usually occursbecause of underlying disease process, infection, or effects oftreatment. Important factor in determining risk of serious infection,especially bacterial infection, is neutropenia (absolute neutrophilcount <500 cells/mm³).

Other

Spider Bites

Bite ofbrown recluse spider (L. reclusa) can cause severe local reaction,with fever, pain, and swelling followed by blister formation andnecrosis. Spider is brown, 10–15 mm long, with 6 eyes arrangedin an arc.

Female black widow spider (L. mactans)has red ventral spot and variable red dorsal spots. Usual lengthis about 2 cm, and bite produces twin red fang marks in skin. Injectionof venom produces pain and swelling at site of bite. Vomiting, fever,and intense abdominal pain may occur within 30 mins.

History and identification of spiderconfirm diagnosis.

Serum Sickness

Occurs 1–2wks after exposure to animal serum (e.g., diphtheria antitoxin;botulism antitoxin types A, B, and E; and antivenoms for snake orspider bites). Accelerated reaction may occur within 1–5days in individuals who have had previous exposure.

Clinical manifestations include fever;macular, papular, erythematous, or urticarial rash; localized orgeneralized adenopathy; hepatosplenomegaly; vomiting; abdominalpain; arthralgia or arthritis; and generalized edema. Usually self-limitedillness and lasting few days to few weeks.

Factitious Fever

Sometimes parent or guardian fabricates andreports persistent fever in child. Clues to this diagnosis are

Lack oftachycardia, flushing, sweating, or warm skin at time of fever

Rapid appearance and disappearanceof high fever in child who is otherwise well

Absence of fever when nurse or physiciantakes temperature

Wide discrepancy between oral and rectaltemperatures when taken simultaneously.

In any of these situations, consider Munchausensyndrome by proxy.

Diagnostic Approach: Acute Fever

Most acutefevers are caused by infection, usually viral or bacterial.

Common infections should be consideredbefore less common ones, unless clinical findings suggest otherwise.

Best guide to accurate diagnosis ishistory and physical exam.

Clinical Findings

Age of child,height of fever, compromised host defenses, and associated findings (e.g.,rash, painful extremity, abdominal pain, jaundice, generalized lymphadenopathy,hepatomegaly, or splenomegaly) are important factors in diagnosisof any child who presents with fever.

Important historical information includesany history of contact with other ill individuals, foreign travel,previous immunizations, drug exposure, history of pica, and exposureto animals or birds.

History of pica suggests toxoplasmosis or toxocariasis(visceral larva migrans).

History of tick exposure suggests RockyMountain spotted fever, relapsing fever, or Lyme disease.

History of exposure to animals or birdssuggests diseases caused by rats (plague, rat-bite fever, leptospirosis);hamsters (lymphocytic choriomeningitis encephalitis); rabbits (tularemia);cattle, goats, and dogs (brucellosis); cats (cat scratch disease,toxoplasmosis); and birds (psittacosis).

Age

Risk ofserious bacterial illness (e.g., septicemia and meningitis) varieswith age and is greatest during immediate neonatal period, especiallyin premature infants.

Clinical findings may be nonspecific,including poor feeding, decreased activity, fever, or hypothermia.

In such infants, CBC with differentialand blood, urine, and spinal fluid cultures should be performed.

Gram-stained smear of spinal fluidshould be performed and antigen studies considered.

Chest radiograph should be performedwith history of respiratory symptoms.

Stool culture should be performed withhistory of diarrhea.

Height of Fever

In infants,incidence of serious bacterial infection is higher in those withrectal temperature >41°C compared with those withlower temperature.

Preschool and school-aged childrenoften have high fever that persists for several days and is notassociated with localizing findings. Such children do not appearvery ill and usually have self-limited viral infections.

Continued observation with close follow-upusually clarifies many of these problems.

Whatever the height of fever, assessmentof toxicity and level of functioning is crucial in diagnosis andmanagement.

Compromised Host Defenses

Children with impaired host defenses dueto primary or secondary immunodeficiency disorders are at risk fordevelopment of serious infection caused by wide range of infectiveagents, including bacteria (S. aureus, gram-negative enteric organisms),viruses (cytomegalovirus, VZV), protozoa (P. carinii), and fungi(Candida and Aspergillus species).

Associated Physical Findings

Fever and Rash

Macularor papular rashes occur with viral infection (enteroviruses, herpesvirus6, measles virus, rubella virus, parvovirus B19, Epstein-Barr virus),bacterial infection (scarlet fever, meningococcemia, toxic shocksyndrome, typhoid fever, rat bite fever, leptospirosis), rickettsialinfection (Rocky Mountain spotted fever), Kawasaki disease, anddrug reactions (most commonly penicillins and sulfonamides).

Erythematous rashes occur with viralinfection (parvovirus B19), bacterial infection (scarlet fever,toxic shock syndrome, staphylococcal scalded skin syndrome), Kawasakidisease, and reactions to same drugs causing macular or papularrashes.

Petechial and purpuric rashes occurwith congenital viral infection (rubella virus, cytomegalovirus),other viral infection (enteroviruses, Epstein-Barr virus, arboviruses),bacterial infection (group A Streptococcus, N. meningitidis, S.pneumoniae, N. gonorrhoeae, S. aureus, H. influenzae type b, P. aeruginosaand other gram-negative enteric bacteria), rickettsial infection(Rocky Mountain spotted fever), and parasitic infection (toxoplasmosis).

Vesicular rashes occur with viral infection(herpes simplex virus, varicella-virus infection, enteroviruses)and bacterial infection (bullous impetigo, staphylococcal scaldedskin syndrome).

See Chap.60, Skin Lesions and Rashes.

Fever and Painful Extremity

Infectiousor inflammatory causes

Cellulitis

Septic arthritis

Osteomyelitis

Transient synovitis

Skin/soft tissue abscess

Thrombophlebitis

Acute rheumatic fever

Vaccine immunization

Other causes

Neoplasia (leukemia, osteogenic sarcoma,Ewing sarcoma, metastatic neuroblastoma)

Collagen vascular disease (juvenilerheumatoid arthritis, systemic lupus erythematosus)

Kawasaki disease

Serum sickness

Arthritis associated with inflammatorybowel disease

See Chap.37, Limp.

Fever and Abdominal Pain

Infectiousand inflammatory causes

Nonspecific viral illness

Gastroenteritis

Urinary tract infection

Pneumonia

Appendicitis

Intraabdominal abscess

Hepatitis

Peritonitis

Cholecystitis

Cholangitis

IBD

Pelvic inflammatory disease

Pancreatitis

Generalized vasculitis

Other causes

Neoplasia (leukemia, Hodgkin disease,non-Hodgkin lymphoma, neuroblastoma, hepatic malignancies)

Diabetic ketoacidosis

Black widow spider bite

See Chap.2, Abdominal Pain.

Fever and Jaundice

Most commoncause of fever and unconjugated hyperbilirubinemia in neonates is septicemia.Causes of fever and conjugated hyperbilirubinemia in neonates include

Viral infection(rubella virus, cytomegalovirus, herpes simplex virus, VZV, enteroviruses,hepatitis B virus)

Bacterial infection (septicemia, syphilis)

In infancy and childhood, fever andconjugated hyperbilirubinemia may be due to

Viral infection (hepatitis A, B, C,D, E; enteroviruses; herpes simplex virus; Epstein-Barr virus; cytomegalovirus

Bacterial infection (septicemia, cholecystitis,cholangitis, liver abscess, leptospirosis, brucellosis)

Rickettsial infection (Q fever)

Fungal infection (histoplasmosis)

Parasitic infection (amebiasis, malaria,visceral larval migrans)

Drug reactions

Neoplasia (hepatic malignancies, non-Hodgkinlymphoma)

See Chap.36, Jaundice.

Fever and Generalized Lymphadenopathy

Infectiouscauses

Viralinfection (rubella virus, measles virus, Epstein-Barr virus, cytomegalovirus, VZV,hepatitis A virus, HIV)

Bacterial infection (pyogenic infectionfrom S. aureus, group A Streptococcus, H. influenzae type b, S.pneumoniae; tuberculosis; brucellosis; tularemia; salmonellosis;leptospirosis; syphilis)

Fungal infection (histoplasmosis)

Parasitic infection (toxoplasmosis,malaria)

Noninfectious causes

Neoplasia(leukemia, non-Hodgkin lymphoma, metastatic neuroblastoma)

Langerhans histiocytosis

Collagen vascular disease (juvenilerheumatoid arthritis, systemic lupus erythematosus)

Drug reactions

Serum sickness

Chronic granulomatous disease

Sarcoidosis

See Chap.38, Lymphadenopathy.

Fever with Hepatomegaly, Splenomegaly, or Hepatosplenomegaly

Causes offever and hepatomegaly

Hepatitis (A, B, C, D, E)

Primary liver abscess

Amebiasis

Primary liver malignancies

Causes of fever and splenomegaly

Viral infection(rubella virus, cytomegalovirus, herpes simplex virus, enteroviruses, Epstein-Barrvirus)

Bacterial infection (septicemia, endocarditis,tularemia, plague, salmonellosis, splenic abscess)

Rickettsial infection (Rocky Mountainspotted fever)

Parasitic infection (malaria, toxoplasmosis)

Infectious causes of fever and hepatosplenomegaly

Viral infection(rubella virus; herpes simplex virus; cytomegalovirus; VZV; enteroviruses;Epstein-Barr virus; hepatitis A, B, C, D, E)

Bacterial infection (septicemia, endocarditis,brucellosis, tuberculosis, syphilis, leptospirosis, relapsing fever)

Fungal infection (histoplasmosis, coccidioidomycosis)

Parasitic infection (visceral larvalmigrans, toxoplasmosis, Chagas disease)

Other causes of fever and hepatosplenomegaly

Neoplasia(leukemia, Hodgkin disease, non-Hodgkin lymphoma, neuroblastoma)

Langerhans histiocytosis

Collagen vascular disease (juvenilerheumatoid arthritis, systemic lupus erythematosus)

See Chap.30, Hepatomegaly and Chap. 62, Splenomegaly.

Fever without Localizing Signs

Most childrenwith fever and no apparent focus of infection have self-limitedviral infection that resolves without treatment and has no sequelae.

Small percentage of children with acuteonset of fever ≥39°C and no localizing signs, especiallyat 3–36 mos, may have urinary tract infection, bacteremia,or meningitis.

In infants <1 mo of age, commoncauses of septicemia and meningitis are group B Streptococcus andgram-negative enteric bacteria, commonly E. coli. Much less commonis infection with L. monocytogenes.

At 1–3 mos of age, most commoncauses of septicemia and meningitis are S. pneumoniae, group B Streptococcus,and N. meningitidis.

In children >3 mos of age,S. pneumoniae, N. meningitidis, and Salmonella species (usually occurringwith gastroenteritis) cause most bacterial infections that occurwithout a focus.

Diagnostic and management approachto child with fever without apparent focus of infection dependson age, exposure history, usual pathogens, and severity of illness.

See references at end of chapter forfurther information.

Lab Findings

Lab tests(cultures and radiographs most commonly) are used to confirm diagnostic impressionof infection.

WBC and differential may suggest bacterialor viral infection, but they are not diagnostic. WBC count >20,000/mm³ withpredominance of neutrophils (>70%) or <5,000/mm³ withlarge number of band forms (>5%–10%)suggests bacterial infection. Although similar WBC counts sometimeoccur with viral infections, in such cases there is usually predominanceof lymphocytes and few band forms.

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Source: The Diagnostic Approach to Symptoms and Signs in Pediatrics, 2006

Purpura and Bleeding: Clinical Features and Diagnosis
(The Diagnostic Approach to Symptoms and Signs in Pediatrics)

Loss of Vascular Integrity

In many bleeding disorders, defective hemostasisoccurs at the site of small vessel injury without any abnormalityof coagulation.

Trauma

May producebleeding into skin. After birth trauma, purpura may occur on presenting part—heador extremity.

Young children commonly have bruiseson lower legs from falls.

Nonaccidental trauma (child abuse)should be suspected if bruises or associated fractures are unexplainedby history. Bruises found on buttocks, back, chest, abdomen, orface or in various stages of resolution or conforming to a beltor cord mark are suspicious of child abuse.

Infection

Most commoncauses of fever and petechiae are viral infections and group A streptococcalpharyngitis. Important to exclude meningococcemia and Rocky Mountainspotted fever because these are life-threatening diseases.

S. pneumoniae and H. influenzae typeb infections can present with septic shock and may be clinicallyindistinguishable from meningococcemia. Purpuric lesions also maybe seen with P. aeruginosa and S. aureus as well as N. gonorrhoeaeinfection.

Purpura fulminans, a severe form ofbleeding caused in part by loss of vascular integrity, is characterizedby large ecchymoses and gangrene of extremities. It is often foundin association with disseminated intravascular coagulation (DIC)and may accompany meningococcemia as well as septicemia from otherpathogens.

Henoch-Schönlein Purpura

Vasculitischaracterized by symmetric purpuric rash on buttocks and lower legs.Abdominal pain, arthritis of large joints, and blood in stools arefrequent findings. Hematuria with or without proteinuria also mayoccur.

Platelet count is normal.

Diagnosis is usually clinical.

Drugs

Several drugs (e.g., penicillins and sulfonamides)may cause increased capillary fragility and purpura. Corticosteroidsmay cause purpuric striae.

Langerhans Histiocytosis

Scaly rashwith papules and vesicles that also may be purpuric may occur. Othermanifestations include lymphadenopathy, hepatosplenomegaly, anemia,and thrombocytopenia.

Skin biopsy is diagnostic.

Ehlers-Danlos Syndrome

Caused bymutations in genes that code for collagen, collagen-modifying enzymes, andpossibly other extracellular matrix components.

Beighton et al. (1998) revised classificationin which 6 major types are now described. Most common types areknown as classical, hypermobility, and vascular types. Genetic transmissionis autosomal-dominant.

Classical type is characterized by skin hyperextensibility,joint hypermobility, atrophic scars that widen with age, and easybruising.

Hallmarks of hypermobility type aregeneralized joint hypermobility, hyperextensibility of skin, andchronic joint and limb pain.

Vascular type is characterized by extensivebruising, thin translucent skin, small joint hypermobility, andarterial/intestinal/uterine rupture.

Vitamin C Deficiency

Scurvy israre in U.S.

Occurrence is due to lack of ascorbicacid (vitamin C) in diet.

Characteristic findings include purpura,especially on lower extremities, gingival and soft tissue bleeding,and leg pain and swelling.

Clinical and radiographic findingsalong with low serum vitamin C level are diagnostic.

Hereditary Hemorrhagic Telangiectasia (Osler-Rendu-WeberDisease)

Autosomal-dominantdisorder characterized by multiple telangiectasias of skin and bleedingfrom respiratory and GI tracts. Gene locus of most frequent formhas been mapped to chromosome 9q34.1.

Epistaxis, GI bleeding, and skin bruisingare common findings.

Diagnosis is usually clinical.

Thrombocytopenia

May be due to increased platelet destruction,decreased platelet production, or platelet sequestration. More than1 mechanism may be responsible for thrombocytopenia, especiallywhen considering effects of infection and drugs.

Increased Platelet Destruction

In disorders that cause increased plateletdestruction, large platelets may be seen on blood smear. Exam ofbone marrow usually reveals normal or increased number of megakaryocytes.

Immune-Mediated

Neonatal Alloimmune Thrombocytopenia

About 98% ofpopulation have PL-A1 antigen on platelet surface. When maternal plateletslack this antigen, fetal platelets crossing placenta stimulate productionof maternal antibody, which results in their destruction.

Diffuse purpura usually occur at orsoon after birth.

Maternal platelet count is normal.Platelet typing of parents confirms diagnosis.

Maternal Autoimmune Thrombocytopenia

Maternalantibody crosses placenta, binds to infant's platelets,and destroys them. Maternal platelet count is usually low, whereasinfant platelet counts vary from near normal to <10,000/mm³.

Other than presence of generalizedpetechiae, these infants appear well.

Self-limited and usually resolves by3 mos of age.

Idiopathic Thrombocytopenic Purpura

Often followsonset of viral infections, with peak incidence at 2–6 yrsof age.

Hallmark is presence of purpura, whichcan vary from pinpoint petechiae to large ecchymoses in random distribution.

Antibodies against common plateletglycoproteins bind to platelet membrane, causing platelets to beremoved by tissue macrophages in the spleen. CBC is normal exceptfor marked thrombocytopenia. Platelet count is usually <50,000/mm³ andoften <10,000/mm³.

Bone marrow exam is unnecessary unlessleukemia is suspected.

Presence of epistaxis, gross hematuria,or bloody stools indicates more significant bleeding problem. Intracranialbleeding is most serious complication and is associated with plateletcount of <10,000/mm³.

Association of autoimmune hemolyticanemia or neutropenia with idiopathic thrombocytopenic purpura iscalled Evans syndrome.

Collagen Vascular Disease

Collagen vascular diseases (e.g., systemiclupus erythematosus) may produce immune-mediated thrombocytopenia.In some women with systemic lupus erythematosus, antiplatelet antibodiescross placenta, producing transient neonatal thrombocytopenia.

Drug-Induced Thrombocytopenia

Immune-mediated thrombocytopenia may be dueto drugs (e.g., sulfonamides, phenytoin, valproic acid, acetazolamide,carbamazepine, and quinidine). Purpura usually appear within 24hrs of exposure and begin to disappear after discontinuation ofthe drug.

Infection

Infection with several pathogens (see previoussection) may trigger onset of thrombocytopenia with or without DIC.

Hemolytic-Uremic Syndrome

Often aconsequence of diarrheal illness caused by E. coli 0157:H7.

Usual clinical findings include hemolyticanemia, thrombocytopenia, and renal failure.

Blood smear shows fragmented red cells(schistocytes).

Thrombotic Thrombocytopenic Purpura

Similarin many respects to hemolytic-uremic syndrome. However, usuallyoccurs in adults and tends to be chronic and relapsing.

Characterized by thrombocytopenic purpura,microangiopathic hemolytic anemia, and widespread thrombotic occlusionsin microcirculation, primarily in brain and liver.

Wiskott-Aldrich syndrome

Thrombocytopenic purpura, eczema, and impairedcell-mediated immunity with increased susceptibility to infectioncharacterize this X-linked recessive disorder. Platelet count usuallyis <50,000/mm³. See Chap. 53, Recurrent Infection.

Decreased Platelet Production

In disordersthat cause decreased platelet production, platelets in peripheralblood tend to be normal in size or small. Bone marrow exam showsabsence or decreased number of platelets.

In addition to conditions discussedin this section, infection also causes decreased platelet production.

Specific Platelet Disorders

Congenital Amegakaryocytic Thrombocytopenia

Rare disorder characterized by nonimmunethrombocytopenia with decreased marrow megakaryocyte counts. Redcells are macrocytic and fetal hemoglobin levels are increased.Pancytopenia and even leukemia may occur in some cases.

Thrombocytopenia–Absent Radius Syndrome

Neonatal thrombocytopenia and bilateral absenceof radii with presence of both thumbs characterize this autosomal-recessivedisorder.

Bone Marrow Suppression (Generalized)

Drugs, radiation,and infection including septicemia may cause bone marrow suppressionand thrombocytopenia.

Many cancer chemotherapeutic agentscause thrombocytopenia, including cytosine arabinoside, cyclophosphamide,methotrexate, and doxorubicin.

Chloramphenicol may cause dose-dependentreversible bone marrow suppression or dose-independent irreversiblemarrow aplasia.

Aplastic anemia and Fanconi anemiaare discussed in Chap. 45, Pallor(Anemia).

Bone Marrow Replacement

Normal bone marrow may be replaced by leukemiaof all types, metastatic neuroblastoma, and histiocytoses. The resultis platelet destruction and thrombocytopenia. See Chap. 38, Lymphadenopathy.

Megaloblastic Anemia

Folic acid and vitamin B₁₂ deficienciesmay be associated with thrombocytopenia and neutropenia due to inadequateproduction or increased destruction in bone marrow. See Chap. 45, Pallor (Anemia).

Platelet Sequestration

Hypersplenism

Can leadto platelet sequestration and thrombocytopenia.

Common causes include portal hypertensionand storage diseases.

Spleen is enlarged and firm. Plateletcount in such disorders usually is 50,000–100,000/mm³;therefore, significant bleeding is unusual.

Large Hemangiomas

Hemangioma-thrombocytopenia (Kasabach-Merritt)syndrome is autosomal-dominant disorder characterized by large hemangiomas,thrombocytopenia, microangiopathic hemolytic anemia, and consumptionof coagulation factors.

Abnormal Platelet Function

Qualitative platelet disorders should besuspected when platelet count is normal and bleeding time is prolonged.

Thrombasthenia (Glanzmann Disease)

Absenceor deficiency of glycoprotein IIb-IIIa complex is responsible forthis disorder of platelet aggregation. Genetic transmission is usuallyautosomal-recessive, but autosomal-dominant form has been described.Gene locus has been mapped to chromosome 17q21.32.

Usually presents in infancy or childhoodwith multiple bruises and purpura. Recurrent epistaxis and menorrhagiaare also common findings. Platelet count is normal, bleeding timeis prolonged, and platelet aggregation is absent on blood smear.

Assay of glycoprotein IIb-IIIa complexin platelet membrane establishes diagnosis.

Giant Platelet Syndrome (Bernard-Soulier Syndrome)

In thisautosomal-recessive disorder, glycoprotein Ib is absent from plateletmembrane. Also, glycoproteins IX and V have been shown to be deficientin this syndrome.

Characteristic features are easy bruisingand severe bleeding, especially at time of injury or surgery. Mildthrombocytopenia, giant platelets, prolonged bleeding time, anddefective in vitro platelet agglutination with ristocetin are usualfindings.

Demonstration of absence of glycoproteinIb in platelet membrane confirms diagnosis.

Storage Pool Deficiency

Deficiencyin number and contents of dense granules, alpha granules, or both,impairs platelet aggregation.

These rare disorders usually presentin childhood or adolescence with easy bruising and prolonged bleedingfrom minor cuts, epistaxis, or menorrhagia.

Electron microscopy of platelets isdiagnostic.

Drugs

Acetylsalicylic acid (aspirin) causes defectin second phase of platelet aggregation, and bleeding time is prolonged.NSAIDs, valproic acid, and high-dose penicillins also may causeplatelet dysfunction.

Uremia

Purpura as well as mucous membrane and GIbleeding can occur with uremia. Exact cause of platelet defect inuremia is unknown, but in vitro platelet aggregation is abnormaland platelet adhesion is decreased.

Coagulation Disorders

Factor Deficiencies

von Willebrand Disease

Caused byquantitative or qualitative decrease in von Willebrand factor (vWF),which is carrier protein for coagulation factor VIII. Gene for vWFhas been mapped to chromosome 12p13.3.

Superficial bruising, epistaxis, prolongedoozing from minor wounds, and prolonged heavy menstrual periodsmay occur.

Screening tests usually reveal prolongedactivated partial thromboplastin time (aPTT) and bleeding time.

Diagnosis can be confirmed by measuringvWF antigen and vWF ristocetin cofactor. The latter test is measureof vWF functional activity.

Factor VIII Deficiency (Hemophilia A)

Caused bymutations in Factor VIII gene, which has been mapped to Xq28.

Characteristic manifestations includebleeding into joints and muscle as well as prolonged bleeding fromwounds. Excessive bleeding may occur after circumcision; however,evidence of bleeding may not occur until a child begins to walk,when excessive bruising may be noted after frequent falls.

Risk of intracranial bleeding aftereven mild head trauma is always serious concern.

Prolonged aPTT is only abnormal coagulationscreening test, whereas decreased Factor VIII assay confirms diagnosis.

Factor IX Deficiency (Hemophilia B, Christmas Disease)

Factor IXgene has been mapped to Xq27.

Clinical presentation is indistinguishablefrom that of Factor VIII deficiency.

Screening coagulation tests revealprolonged aPTT. Decreased Factor IX assay confirms diagnosis.

Deficiencies of Factors I, II, V, VII, X, XI, and XIII

Clinicalpicture in Factor I deficiency is similar to that of platelet disorders,with bruising, epistaxis, and mucous membrane bleeding. Intracranialor joint bleeding is rare. Prothrombin time (PT), aPTT, and bleedingtime are prolonged. Prolongation of either thrombin time or reptilasetime or both should suggest this disorder. Very low or absent serumfibrinogen confirms diagnosis.

Factor II, V, VII, and X deficienciesmay present with easy bruising or prolonged bleeding after trauma,surgery, or dental work. Prolonged PT occurs and diagnosis is confirmedby factor assay. aPTT is normal with Factor VII deficiency, whereasboth PT and aPTT are prolonged with Factor II, V, and X deficiencies.

In Factor XI deficiency, mild bleedingincluding epistaxis or menorrhagia may occur. aPTT is prolongedand specific factor assay is diagnostic.

Easy bruising, prolonged umbilicalcord bleeding, and sometimes GI bleeding occur with Factor XIIIdeficiency. Screening coagulation tests are normal. Specific factorassay is diagnostic.

Vitamin K Deficiency

Resultsin failure of vitamin K–dependent coagulation factors (II,VII, IX, and X) to develop calcium-binding sites, which are necessaryfor effective coagulation function.

Because newborns have low vitamin Kstores, failure to give vitamin K immediately after birth may causegeneralized bleeding between 2 and 4 days of age. Hematochezia,melena, hematemesis, or bleeding from other sites also may occur.

History of failure to give vitaminK at birth; normal platelet count; normal or prolonged bleedingtime; prolonged PT and aPTT; decreased Factors II, VII, IX, andX; and reversal of prolonged PT and aPTT with decreased subsequentbleeding after vitamin K administration confirm diagnosis.

In infancy, childhood, and adolescence,causes of vitamin K deficiency include liver disease with cholestasisand fat malabsorption, prolonged antibiotic usage, and cystic fibrosis.Some clinical findings are easy bruising and ecchymoses as wellas mucous membrane and visceral hemorrhage. PT and aPTT are prolonged,whereas coagulation factors II, VII, IX, and X are decreased.

Disseminated Intravascular Coagulation

More commoncauses are septicemia, shock, and massive trauma.

Bleeding is secondary to consumptionof coagulation factors and platelets. Bruising, oozing from venipuncturesites, mucous membrane bleeding, and purpura may occur.

Certain lab findings confirm diagnosis:decreased platelet count; prolonged PT, aPTT, and bleeding time;decreased serum fibrinogen; increased fibrin split products; anddecreased Factors V and VIII.

Liver Disease

Coagulationabnormalities in acute liver failure include decreased synthesisof coagulation factors (the liver is site of synthesis of all coagulationfactors except Factor VIII); vitamin K malabsorption and decreasedactivity of Factors II, VII, IX, and X secondary to cholestasis;thrombocytopenia secondary to hypersplenism; production of abnormalfibrinogens; and DIC.

Bleeding as well as purpura may occur.

Lab findings usually show thrombocytopenia;prolonged PT, aPTT, and bleeding time; low serum levels of prothrombinand fibrinogen; and decreased serum levels of Factors V, VII, IX,and X.

Circulating Anticoagulants

May be associated with viral infections,malignancy, and collagen vascular disease. Usually prolonged aPTTfails to correct after adding normal plasma in test tube. In affectedindividuals, bleeding is uncommon, especially those with lupus anticoagulants.

Diagnostic Approach

Age, clinical findings, family history, andscreening tests (CBC with differential, platelet count, analysisof blood smear, PT and aPTT, and standardized Ivy bleeding time)are either diagnostic or narrow diagnostic possibilities in individualspresenting with purpura and bleeding.

Age

Neonates,especially preterm infants, have some features that may predisposeto purpura and bleeding. They have increase in capillary fragilityand decrease in platelet aggregation. Concentrations of vitaminK–dependent clotting factors are lower than adult normalvalues.

Diagnostic approach to purpura andbleeding depends on whether neonate is well or ill and whether plateletcount is normal or decreased.

In well neonate with normal platelet count,most common disorders that cause bleeding are trauma, vitamin Kdeficiency, Factor VIII or IX deficiency, and in utero exposureto drugs taken by mother (e.g., acetylsalicylic acid, phenytoin,or coumadin).

In well neonate with decreased plateletcount, most common disorders are alloimmune thrombocytopenia andmaternal autoimmune thrombocytopenia.

In ill neonate, common causes of bleedingand purpura are severe birth trauma, septicemia, and DIC. Othercauses include congenital infection (herpes simplex, cytomegalovirus,rubella, toxoplasmosis, syphilis), congenital leukemia, and osteopetrosis.

In infancy, childhood, and adolescence,most common causes of purpura and bleeding are accidental trauma,child abuse, Henoch-Schönlein purpura, idiopathic thrombocytopenicpurpura, leukemia, infection, and Factor VIII and IX deficiencies.

Clinical Findings

Typically,individuals with loss of vascular integrity have superficial bleedingwith purpura. Diagnosis of loss of vascular integrity depends onclinical recognition of vascular disorder and absence of plateletor coagulation disorder.

Individuals with thrombocytopenia orplatelet dysfunction usually have purpura and superficial bleedingof mucous membranes including epistaxis and GI tract bleeding. Alsomay have hematuria, menorrhagia, and intracranial bleeding. Normalplatelet count with prolonged bleeding time suggests qualitativeplatelet defect.

Individuals with Factor VIII or IXdeficiency, which are most common coagulation disorders, have recurrentbruising and bleeding into joints and muscle.

Family History

Positivefamily history may help confirm diagnosis.

As general rule, genetically transmitteddisorders usually have their onset in infancy with appearance ofrecurrent purpura and bleeding.

Acquired disorders are usually acute,variable in time of onset, and typically associated with infection,drug reactions, malignancy, or immunologic disorders.

Screening and Diagnostic Tests

A plateletcount of <150,000/mm³ isabnormal. Bleeding is rare with platelet count of >30,000/mm³.Large platelets are usually seen on blood smear in disorders inwhich thrombocytopenia is due to increased platelet destruction.Normal-sized platelets are usually seen in disorders in which thrombocytopeniais due to decreased production. When thrombocytopenia is associatedwith neutropenia or pancytopenia, bone marrow aspirate should beperformed searching for evidence of aplastic anemia, leukemia, orother malignancies.

With normal platelet count but abnormalbleeding time, most likely diagnoses are von Willebrand disease,aspirin ingestion, qualitative defect in platelet function, anduremia. Tests for renal function, vWF antigen, vWF ristocetin cofactor,and platelet function should be considered.

Possible causes of prolonged PT includeFactor VII deficiency, mild vitamin K deficiency, and liver disease.

Prolonged aPTT may be caused by FactorVIII, IX, XI, and XII deficiencies; von Willebrand disease; andpresence of circulating anticoagulant. There is no clinical bleedingwith Factor XII deficiency.

Possible causes of prolonged PT andaPTT include liver disease, DIC, vitamin K deficiency, congenitalfactor deficiencies (II, V, and X), and fibrinogen disorders (afibrinogenemia,hypofibrinogenemia). Liver function tests should be performed withsuspected liver disease. Otherwise, thrombin time, serum fibrinogen,fibrin split products, and assays for Factors II, V, and X shouldbe performed as indicated. Serum fibrinogen is decreased in congenitalafibrinogenemia, DIC, and sometimes in severe liver disease.

>>>>>>

» READ BOOK EXCERPT ONLINE »

Source: The Diagnostic Approach to Symptoms and Signs in Pediatrics, 2006

Purpura: History and physical examination
(Nursing: Interpreting Signs and Symptoms)

Ask the patient when he first noticed the lesion and whether he has noticed other lesions on his body. Does he or his family have a history of bleeding disorders or easy bruising? Find out what medications he's taking, if any, and ask him to describe his diet. Ask about recent trauma or transfusions and the development of associated signs, such as epistaxis, bleeding gums, hematuria, and hematochezia. Also ask about systemic complaints that may suggest infection, such as a fever. If the patient is female, ask about heavy menstrual flow.

Inspect the patient's entire skin surface to determine the type, size, location, distribution, and severity of purpuric lesions. Also inspect the mucous membranes. Remember that the same mechanisms that cause purpura can also cause internal hemorrhage, although purpura isn't a cardinal indicator of this condition.

» READ BOOK EXCERPT ONLINE »

Source: Nursing: Interpreting Signs and Symptoms, 2007

Fever [Pyrexia]: History and physical examination
(Nursing: Interpreting Signs and Symptoms)

If the patient's fever is only mild to moderate, ask him when it began and how high his temperature reached. Did the fever disappear, only to reappear later? Did he experience other symptoms, such as chills, fatigue, or pain?

» READ BOOK EXCERPT ONLINE »

Source: Nursing: Interpreting Signs and Symptoms, 2007

FEVER: Approach to the Diagnosis
(Differential Diagnosis in Primary Care)

There are certain things to remember when a patient with fever is approached. First, a mild elevation up to 100.5^∘F (38^∘C) rectally may be normal in some people. Second, one should rule out malingering by the patient or incorrect recording by hospital personnel. Finally, psychogenic disorders must be ruled out. The duration and severity of the fever are important. If possible, a careful chart of the fever should be made with the patient off all drugs (especially aspirin and steroids). Conditions with intermittent or relapsing fever such as brucellosis, malaria, and Mediterranean fever will be elucidated in this fashion (see Table 28). The association with other symptoms is important. Fever, right upper quadrant pain, and jaundice suggest cholecystitis or cholangitis, whereas fever with right-sided flank pain suggests pyelonephritis. After taking a few moments to jot down the differential before launching into the history and physical examination, one can question and examine the patient more appropriately. The differential diagnosis will also lead to more appropriate use of laboratory testing.

» READ BOOK EXCERPT ONLINE »

Source: Differential Diagnosis in Primary Care, 2007

» Next page: Signs of Marburg virus

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TREATMENTS & RESEARCH

Dr. Huntley's Diagnosis Checklist

Diagnosis of Marburg virus

Marburg virus Diagnosis: Book Excerpts

Tests and diagnosis discussion for Marburg virus:

Diagnostic Tests for Marburg virus: Online Medical Books

PURPURA AND ABNORMAL BLEEDING: Ask the Following Questions: (Algorithmic Diagnosis of Symptoms and Signs)

DIAGNOSTIC WORKUP

FEVER, ACUTE: Ask the Following Questions: (Algorithmic Diagnosis of Symptoms and Signs)

DIAGNOSTIC WORKUP

FEVER, CHRONIC: Ask the Following Questions: (Algorithmic Diagnosis of Symptoms and Signs)

DIAGNOSTIC WORKUP

Fever: Differential Diagnosis (In a Page: Signs and Symptoms)

Workup and Diagnosis

Purpura: Differential Diagnosis (In a Page: Signs and Symptoms)

Workup and Diagnosis

Rash with Fever: Differential Diagnosis (In a Page: Signs and Symptoms)

Workup and Diagnosis

Purpura: Differential Diagnosis (In A Page: Pediatric Signs and Symptoms)

Workup and Diagnosis

Fever – Cyclic: Differential Diagnosis (In A Page: Pediatric Signs and Symptoms)

Workup and Diagnosis

Fever – Recurrent: Differential Diagnosis (In A Page: Pediatric Signs and Symptoms)

Workup and Diagnosis

Fever – Unknown Origin: Differential Diagnosis (In A Page: Pediatric Signs and Symptoms)

Workup and Diagnosis

Fever – Acute: Differential Diagnosis (In A Page: Pediatric Signs and Symptoms)

Workup and Diagnosis

FEVER: Approach to the Diagnosis (Differential Diagnosis in Primary Care)

Fever: History and physical examination (Handbook of Signs & Symptoms (Third Edition))

Purpura: History and physical examination (Handbook of Signs & Symptoms (Third Edition))

Allergic purpuras: Diagnosis (Professional Guide to Diseases (Eighth Edition))

Colorado tick fever: Diagnosis (Professional Guide to Diseases (Eighth Edition))

Idiopathic thrombocytopenic purpura: Diagnosis (Professional Guide to Diseases (Eighth Edition))

Lassa fever: Diagnosis (Professional Guide to Diseases (Eighth Edition))

Relapsing fever: Diagnosis (Professional Guide to Diseases (Eighth Edition))

Rheumatic fever and rheumatic heart disease: Diagnosis (Professional Guide to Diseases (Eighth Edition))

Rocky Mountain spotted fever: Diagnosis (Professional Guide to Diseases (Eighth Edition))

Purpura: History and physical examination (Professional Guide to Signs & Symptoms (Fifth Edition))

Fever [Pyrexia]: History and physical examination (Professional Guide to Signs & Symptoms (Fifth Edition))

Fever: History (The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter)

Physical examination

Rash Accompanied by Fever: History (The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter)

Physical examination

Petechiae and Purpura: History (The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter)

Physical examination

Purpura/Petechiae/Excessive Bleeding: Differential Overview (Field Guide to Bedside Diagnosis)

Diagnostic Approach

Fever of Unknown Origin: Differential Overview (Field Guide to Bedside Diagnosis)

Diagnostic Approach

Allergic purpura: Diagnosis (Handbook of Diseases)

Idiopathic thrombocytopenic purpura: Diagnosis (Handbook of Diseases)

Rheumatic fever and rheumatic heart disease: Diagnosis (Handbook of Diseases)

Fever: History (Alarming Signs and Symptoms: Lippincott Manual of Nursing Practice Series)

Physical examination

Fever: History (Signs & Symptoms: A 2-in-1 Reference for Nurses)

Purpura: History (Signs & Symptoms: A 2-in-1 Reference for Nurses)

Fever: Clinical Features and Diagnosis: Acute Fever (The Diagnostic Approach to Symptoms and Signs in Pediatrics)

Common Causes

Infectious

Noninfectious

Drug Reactions

Vaccine Reactions

Trauma

Burns

Kawasaki Disease

Uncommon Causes

Infectious

Hantavirus Pulmonary Syndrome

Borrelia (Relapsing Fever)

Brucellosis

Leptospirosis

Plague

Psittacosis (Ornithosis)

Rat-Bite Fever

Syphilis

Tularemia

Malaria

Ascariasis

Toxocariasis (Visceral Larva Migrans, Ocular Larva Migrans)

TREATMENTS &
RESEARCH

Dr. Huntley's
Diagnosis
Checklist

PURPURA AND ABNORMAL BLEEDING: Ask the Following Questions:
(Algorithmic Diagnosis of Symptoms and Signs)

FEVER, ACUTE: Ask the Following Questions:
(Algorithmic Diagnosis of Symptoms and Signs)

FEVER, CHRONIC: Ask the Following Questions:
(Algorithmic Diagnosis of Symptoms and Signs)

Fever: Differential Diagnosis
(In a Page: Signs and Symptoms)

Purpura: Differential Diagnosis
(In a Page: Signs and Symptoms)

Rash with Fever: Differential Diagnosis
(In a Page: Signs and Symptoms)

Purpura: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

Fever – Cyclic: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

Fever – Recurrent: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

Fever – Unknown Origin: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

Fever – Acute: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

FEVER: Approach to the Diagnosis
(Differential Diagnosis in Primary Care)

Fever: History and physical examination
(Handbook of Signs & Symptoms (Third Edition))

Purpura: History and physical examination
(Handbook of Signs & Symptoms (Third Edition))

Allergic purpuras: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

Colorado tick fever: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

Idiopathic thrombocytopenic purpura: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

Lassa fever: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

Relapsing fever: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

Rheumatic fever and rheumatic heart disease: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

Rocky Mountain spotted fever: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

Purpura: History and physical examination
(Professional Guide to Signs & Symptoms (Fifth Edition))

Fever [Pyrexia]: History and physical examination
(Professional Guide to Signs & Symptoms (Fifth Edition))

Fever: History
(The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter)

Rash Accompanied by Fever: History
(The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter)

Petechiae and Purpura: History
(The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter)

Purpura/Petechiae/Excessive Bleeding: Differential Overview
(Field Guide to Bedside Diagnosis)

Fever of Unknown Origin: Differential Overview
(Field Guide to Bedside Diagnosis)

Allergic purpura: Diagnosis
(Handbook of Diseases)

Idiopathic thrombocytopenic purpura: Diagnosis
(Handbook of Diseases)

Rheumatic fever and rheumatic heart disease: Diagnosis
(Handbook of Diseases)

Fever: History
(Alarming Signs and Symptoms: Lippincott Manual of Nursing Practice Series)

Fever: History
(Signs & Symptoms: A 2-in-1 Reference for Nurses)

Purpura: History
(Signs & Symptoms: A 2-in-1 Reference for Nurses)

Fever: Clinical Features and Diagnosis: Acute Fever
(The Diagnostic Approach to Symptoms and Signs in Pediatrics)

Purpura and Bleeding: Clinical Features and Diagnosis
(The Diagnostic Approach to Symptoms and Signs in Pediatrics)