Lesson 2

Scarlet fever. Pseudotuberculosis


Scarlet Fever.

This disease is the result of infection by streptococci that elaborate one of three pyrogenic (erythrogenic) exotoxins.


Β-hemolytic streptococcus group A


The incubation period ranges from 17 days, with an average of 3 days. The onset is acute and is characterized by fever, vomiting, headache, toxicity, pharyngitis, and chills. Abdominal pain may be present; when this is associated with vomiting prior to the appearance of the rash, an abdominal surgical condition may be suggested. Within 1248 hr the typical rash appears.

Generally, temperature increases abruptly and may peak at 39.640º C (103104º F) on the 2nd day and gradually returns to normal within 57 days in the untreated patient; it is usually normal within 1224 hr after initiation of penicillin therapy. The tonsils are hyperemic and edematous and may be covered with a gray-white exudate.


Group A streptococcal pharyngitis with inflammation of the tonsils and uvula.


The pharynx is inflamed and covered by a membrane in severe cases. The tongue may be edematous and reddened. During the early days of illness the dorsum of the tongue has a white coat through which the red and edematous papillae project (i.e., white strawberry tongue). After several days the white coat desquamates; the red tongue studded with prominent papillae persists (i.e., red strawberry tongue, raspberry tongue). The palate and uvula may be edematous, reddened, and covered with petechiae.


This is the typical "white strawberry tongue" of scarlet fever,

with a white coating with red dots on the surface.


Red tongue with red dots (red strawberry tongue)


Note inflammation of the oropharynx with petechiae on the soft palate, small red spots caused by group A streptococcal pharyngitis.






The exanthem is red, is punctate or finely papular, and blanches on pressure. In some individuals, it may be palpated more readily than it is seen, having the texture of gooseflesh or coarse sandpaper. The rash appears initially in the axillae, groin, and neck but within 24 hr becomes generalized. Punctate lesions generally are not present on the face. The forehead and cheeks appear flushed, and the area around the mouth is pale (i.e., circumoral pallor). The rash is most intense in the axillae and groin and at pressure sites. Petechiae may occur owing to capillary fragility. Areas of hyperpigmentation that do not blanch with pressure may appear in the deep creases, particularly in the antecubital fossae (i.e., pastia lines). In severe disease, small vesicular lesions (miliary sudamina) may appear over the abdomen, hands, and feet.




Typical rashes in scarlet fever



Flushed face, circumoral pallor (Filatovs sign)

image014 IMG_43a

Pastia lines in skin folds



Miliary sudamina and sand paper or goose skin (shagreen) sign



In people with very dark skin, the inflammation

and redness of exanthem is more subtle,

but the rash is easily seen and felt by the touch.


Desquamation begins on the face in fine flakes toward the end of the 1st wk and proceeds over the trunk and finally to the hands and feet. The duration and extent of desquamation vary with the intensity of the rash; it may continue for as long as 6 wk.


Desquamation on the skin (fine flakes)




Desquamation on the palms and soles (macrolamellar)




This image displays the previously pink, sandpaper-like rash of scarlet fever starting to peel and improve.


Scarlet fever may follow infection of wounds (i.e., surgical scarlet fever), burns, or streptococcal skin infection. Clinical manifestations are similar to those just described, but the tonsils and pharynx generally are not involved. A similar picture may be observed with certain strains of staphylococci that produce an exfoliative toxin.

Scarlet fever must be differentiated from other exanthematous diseases, including measles (characterized by its prodrome of conjunctivitis, photophobia, dry cough, and Koplik spots), rubella (disease is mild, postauricular lymphadenopathy usually is present, and throat culture is negative), and other viral exanthems. Patients with infectious mononucleosis, have pharyngitis, rash, lymphadenopathy, and splenomegaly as well as atypical lymphocytes. The exanthems produced by several enteroviruses can be confused with scarlet fever, but differentiation can be established by the course of the disease, the associated symptoms, and the results of culture. Roseola is characterized by the cessation of fever with the onset of rash and the transient nature of the exanthem. Kawasaki disease, drug eruption, and toxic shock syndrome must also be considered.


Septic or severe scarlet fever associated with bacteremia or toxemia may manifest high fever and may be complicated by arthritis, jaundice, and hydrops of the gallbladder. Scarlet fever may be differentiated from Kawasaki disease by an older age at onset, absence of conjunctival involvement, and recovery of group A streptococci. Streptococcal toxic shocklike syndrome, associated with the pyrogenic toxins, produces toxicity, fever, shock, tissue injury (necrotizing fasciitis, myositis), pneumonia, rash (local or diffuse erythema, maculopapular, petechial, desquamation), and multiorgan dysfunction (kidney, lung, central nervous system). The shock, local tissue injury, older age, and nonscarlatiniform rash differentiate this syndrome from scarlet fever. Arcanobacterium haemolyticum (formerly Corynebacterium haemolyticum) also produces tonsillitis, pharyngitis, and a scarlatiniform rash in adolescents and young adults. Severe sunburn can also be confused with scarlet fever.

DIAGNOSIS. Although 30% of children with sore throat have a positive throat culture for group A streptococci, only 50% of these have a positive antibody response indicative of active infection rather than colonization. Streptococcal pharyngitis is suggested by age greater than 5 yr, high fever, exudates, tender anterior cervical lymphadenopathy, scarlatiniform rash, and a history of exposure. However, only 15% of children with pharyngitis and 25% of those with exudates have streptococcal infection; 50% of those with streptococcal pharyngitis do not have tonsillar exudates. Clinical judgment does not predict which children may have streptococcal infection, which must be diagnosed by throat culture or antigen detection.


Throat culture is the most useful laboratory aid in reaching a diagnosis in patients with acute tonsillitis or pharyngitis. Selective media give a higher yield than sheep blood agar plates. A positive result for a throat culture may indicate streptococcal pharyngitis, but hemolytic streptococci are common inhabitants of the nasopharynx in well children. Isolation of a group A streptococcus from the pharynx of a child with pharyngeal infection does not necessarily indicate that the disease is caused by this organism. When streptococci are isolated from children with moderate or severe exudative pharyngitis who have petechiae on the palate and cervical adenitis, the diagnosis is more secure. Rapid antigen detection tests are not sufficiently sensitive to be used without a back-up culture. Treatment is, however, recommended for all children with pharyngitis and a positive throat culture or rapid antigen test for group A streptococci, even though in some cases the streptococci represent colonization.


The immunologic response of the host after exposure to streptococcal antigen can be assessed by measuring antistreptolysin O (ASO) titers. An increase in ASO titer to greater than 166 Todd units occurs in more than 80% of untreated children with streptococcal pharyngitis within the first 36 wk following infection. This response may be modified or abolished by early and effective antibiotic therapy. ASO titers may be very high in patients with rheumatic fever; in contrast, they are weakly positive or not elevated at all in patients with streptococcal pyoderma; responses in patients with glomerulonephritis are variable. Group A b-hemolytic streptococci also may be recovered from the pharynx of asymptomatic individuals who develop an antibody response to this organism, indicating that subclinical infection has occurred.


Individuals with impetigo may react strongly to stimulation by other streptococcal extracellular products. Anti-DNase (deoxyribonuclease) B provides the best serologic test for streptococcal pyoderma; it begins to rise 68 wk after infection. Most patients with streptococcal pharyngitis also develop elevated titers to this enzyme. Patients with pyoderma and pharyngitis also may develop antibody responses to hyaluronidase, but antihyaluronidase (AH) titers are elevated with less regularity than are ASO titers.


A 2-min, inexpensive Streptozyme slide test (Wampole Laboratories, Cranbury, NJ) is designed to detect antibodies against multiple streptococcal extracellular antigens. This test detects more patients with increased antibody titers than any other single test presently available. Nonspecific (false-positive) reactions have been limited in number, and the test is capable of detecting antibody responses within 710 days of infection. However, the strength of the Streptozyme reagent varies from lot to lot, and it may not be specific for antibodies to extracellular products of group A streptococci.

The white blood cell count may or may not be elevated. Because leukocytosis may occur in many bacterial and viral diseases, this finding is nonspecific. Similarly, elevations in the erythrocyte sedimentation rate and C-reactive protein do not help to establish a specific diagnosis.




Acute pharyngitis that is indistinguishable clinically from that caused by group A b-hemolytic streptococci may be caused by many viruses, including Epstein-Barr virus (infectious mononucleosis). A viral cause may be suggested by failure to isolate streptococci and can be identified specifically by viral culture and serologic studies. Infectious mononucleosis may be suggested by the clinical manifestations, the presence of atypical lymphocytes in the peripheral blood, and a rise in heterophil and Epstein-Barr viral antibody titers. Acute pharyngitis similar to that caused by b-hemolytic streptococci may occur in patients with diphtheria, tularemia, toxoplasmosis, infection with Mycoplasma or A. haemolyticum, and, rarely, in individuals with tonsillar tuberculosis, salmonellosis, and brucellosis or infections caused by Neisseria gonorrhoeae, Neisseria meningitidis, and Yersinia enterocolitica. These diseases can be differentiated by appropriate cultures and serologic tests.


Streptococcal pyoderma must be differentiated from staphylococcal skin disease. Often these bacterial species coexist. The lesions produced are clinically indistinguishable; distinction is made only by culture.

Streptococcal septicemia, meningitis, septic arthritis, and pneumonia present signs and symptoms similar to those produced by other bacterial organisms. The offending pathogen can be established only by culture.


Vinsents angina need to be differentiated from streptococcal angina in Scarlet fever

COMPLICATIONS. Complications generally reflect extension of streptococcal infection from the nasopharynx. This may result in sinusitis, otitis media, mastoiditis, cervical adenitis, retropharyngeal or parapharyngeal abscess, or bronchopneumonia. Hematogenous dissemination of streptococci may cause meningitis, osteomyelitis, or septic arthritis. Nonsuppurative late complications include rheumatic fever and glomerulonephritis.


PREVENTION. Administration of penicillin will prevent most cases of streptococcal disease if the drug is provided prior to the onset of symptoms. Except for rheumatic fever (see Chapter 175), indications for prophylaxis are not clear. Oral penicillin G or V (400,000 U/dose) is provided four times each day for 10 days. Alternatively, 600,000 U of benzathine penicillin in combination with 600,000 U of aqueous procaine penicillin may be given as a single intramuscular injection. This approach should be used for institutional epidemics. Children exposed to an individual case at school may be observed carefully.


Management of carriers of group A b{beta}-hemolytic streptococci is controversial. It has been suggested that treatment of the carrier precludes the development of type-specific immunity, thereby leaving the individual susceptible to reinfection later in life. It is probably unnecessary to re-treat asymptomatic convalescent patients with persistently positive throat cultures for group A streptococci, since they are generally carriers who do not have persistent or recurrent streptococcal infections. Children thought to have recurrent streptococcal infections may be carriers who have frequent viral respiratory infections masquerading as streptococcal infections. Parental anxiety may be high after several such episodes. Treatment with a non-penicillin antibiotic (e.g., cephalosporin, erythromycin, clindamycin) may be useful in eradicating the carrier state but should be reserved for the rare problem case.

No streptococcal vaccines are available for clinical use.

TREATMENT. The goals of therapy are to decrease symptoms and prevent septic, suppurative, and nonsuppurative complications. Penicillin is the drug of choice for the treatment of streptococcal infections. All strains of group A b{beta}-hemolytic streptococci isolated to date have been sensitive to concentrations of penicillin achievable in vivo.

Blood and tissue levels of penicillin sufficient to kill streptococci should be maintained for at least 10 days. Children with streptococcal pharyngitis should be treated with penicillin (125250 mg/dose three times a day) for 10 days. Penicillin G or penicillin V may be employed; the latter is preferable because satisfactory blood levels are achieved even when the stomach is not empty. A single intramuscular injection of a long-acting benzathine penicillin G (600,000 U for children <60 lb and 1,200,000 U for children >60 lb) may be more effective for treatment or prevention of relapse and is indicated for all noncompliant patients or those having nausea, vomiting, or diarrhea.

Erythromycin (40 mg/kg/24 hr), clindamycin (30 mg/kg/24 hr), or cefadroxil monohydrate (15 mg/kg/24 hr) may be used for treating streptococcal pharyngitis in patients who are allergic to penicillin. Generally, relapse rates are lower with regimens other than penicillin. Tetracyclines and sulfonamides should not be used for treatment, although sulfonamides may be used for prophylaxis of rheumatic fever.

Treatment failure, defined as persistence of streptococci after a complete course of penicillin, occurs in 520% of children and is more common with oral than with intramuscular therapy. It may be due to poor compliance, reinfection, the presence of b{beta}-lactamaseproducing oral flora, tolerant streptococci, or presence of a carrier state. Persistent carriage of streptococci predisposes a small number of patients to symptomatic relapse. Repeating the throat culture after a course of penicillin therapy is indicated only in high-risk situations, such as in patients with a history of previous rheumatic fever. If the throat culture is again positive for group A streptococci, some clinicians recommend a second course of treatment. Persistence after a second course of antibiotics probably indicates a carrier state, which has a low risk for the development of rheumatic fever and does not require further therapy.

Patients with severe scarlet fever, streptococcal bacteremia, pneumonia, meningitis, deep soft tissue infections, erysipelas, streptococcal toxic shock syndrome, or complications of streptococcal pharyngitis should be treated parenterally with penicillin, preferably intravenously. The dose and duration of therapy must be tailored to the nature of the disease process, with daily doses as high as 400,000 U/kg/24 hr required in the most severe infections. Severe, necrotizing infections may require the addition of a second antibiotic (e.g., clindamycin) to ensure complete bacterial killing.


PROGNOSIS. The prognosis for adequately treated streptococcal infections is excellent; most suppurative complications are prevented or readily treated. When therapy is provided promptly, nonsuppurative complications are prevented and complete recovery is the rule. In rare instances, particularly in neonates or in children whose response to infection is compromised, fulminant pneumonia, septicemia, and death may occur despite usually adequate therapy.


Short statement of the material

Scarlet fever is an acute infectious disease, that is caused by group A b-hemolytic streptococcus, transmitted by an air-droplet way, characterized by intoxication, rashes on a

skin, tonsillitis, regional lymphadenitis, and strawberry tongue.

Etiology: group A b-hemolytic streptococcus (GABHS).


- source of infection ill person not only with scarlet fever, but other forms of GABHS infections (sore throat, erysipelas, streptodermia).

- infection is transmitted by inhalation of infected airborne droplets, rare with food and direct contact.

- susceptible organism children 2-9 years old.


Pathogenesis An entrance gate is the mucus membrane of the throat, seldom damaged skin, and maternity ways (at delivery).

Pathogenesis has three lines:

1.                     Toxic (toxically damage of cardiovascular, central nervous, endocrine systems).

2.                     Septic primary inflammation in the place of infection (tonsillitis, secondary bacterial complication).

3.                     Allergic sensibilization by GABHS proteins (depression of immunity leads to allergic complications nephritis, arthritis, myocarditis, rheumatism).

Clinical presentation: Onset is usually acute and is characterized by a sore throat (often with dysphagia), fever (often above 39 C), pharyngeal and purulent tonsilar exudates. Anterior cervical lymph nodes, particularly the jugular-digastric nodes just beneath the angle of the mandible, are tender and enlarged. Erythema of the soft palate is common, and an enanthema of doughnut lesions on the soft palate. Strawberry tongue. Other features are nausea and vomiting, headache, abdominal discomfort. One to two days later the rashes like sandpaper appears, first on the neck and then on the trunk and extremities till the end of the day.

The eruption is characterized by dusky red, blanching tiny papules that have a rough texture. Papules are usually absent on the face, palms, and soles, but the face characteristically shows flushing with circumoral pallor. On the body, the rashes are intensified in skin folds and at sites of pressure. In the antecubital and axillary fosses, linear petechias are seen with accentuation of the erythema (Pastias lines).

The exanthema usually lasts 4 to 5 days and then begins to desquamate, first on the face last on the palms and soles. Pharyngitis usually resolves in 5 to 7 days.

Clinical diagnostic criteria:

1. Latent period: a few hours 7 days.

2. Initial or prodromal period (from the first signs of illness to rashes appearance):

up to 1-2 days

acute beginning;

toxic syndrome, hyperthermia;

in the throat: pain, bright hyperemia, pin-point enanthema,

catarrhal regional lymphadenitis (photo).



3. Period of exanthema (rashes):

) Phase of height (1 - 2 days)

maximal intoxication, fever up to 39-40 C;

tonsillitis: bright hyperemia of the throat marked off a hard palate (photo 31), pinpoint enanthema, hypertrophied tonsils, catarrhal, lacunar (photo 32, 33), follicle (photo 34, 35) or necrotizing (photo 36) tonsillitis;

regional lymphadenitis;

pin-point rashes for a few hours spread all over the body, intensified on the front and lateral surface of neck, lateral surfaces of trunk (photo 37), abdomen (photo 38, 39), lumbar region (photo 40, 41), in natural skin folds (photo 42), on the red background of skin, typical intensified in skin folds with hemorrhagic elements (Pastias lines) (photo 43), a skin is rough (sand paper sign), pale perioral triangle (Filatovs sign) (photo 44, 45);

white dermatographia;

coated tongue (photo 46) within 2-3 days clears up (photo 47, 48), on 4th - 5th day becomes strawberry (photo 49, 50);

sympatic phase of scarlet fever heart (tones are loud, tachycardia, BP is elevated).




bright hyperemia of the throat marked off a hard palate



pin-point enanthema


Follicular tonsillitis


Lacunar tonsillitis


Necrotizing tonsillitis


Typical rashes localization



pin-point rashes



Typical rashes localization



Typical rashes localization in skin folds



Typical rashes localization in skin folds



Pale perioral triangle



Coated tongue



Tongue begin to clear up



Strawberry tongue


b) Fading phase:

normalization of body temperature till 3rd - 4th day of the disease, decrease of the toxic syndrome;

rashes and redness of the skin from 2nd - 3rd up to 6th day turns pale;

throat: enanthema disappears from 2nd - 3rd day, hyperemia turns pale till 6-7 day;

the sizes of lymphnodes normalized till 4th - 5th day;

vagus-phase of scarlet fever heart (bradycardia, dilation of the cardiac dullness borders, systolic murmur on the apex, low BP);

a tongue turns pale till 10th - 12th day, with enlarged follicles.


4. Period of recovery: from 2nd week (for 10-14 days)

changes on the skin: flakes-like desquamation all over the body except palms and soles (where it is larger) (photo 51);

tongue with enlarged follicles;

the vagus-phase of scarlet fever heart continue for 2-4 weeks;

rise sensitivity to the streptococcus infection, possibility of complications.


1. Form:

a) typical;

b) atypical:

without rashes;


extra pharyngeal (burns, wounds, post-natal, after operations, delivery);

with aggravated symptoms (hypertoxic, hemorrhagic).

2. Severity:

a) mild;

b) moderate;

c) severe: toxic, septic, toxic-septic.

3. Course:

a) smooth;

b) uneven (relapses, complications).



By the character:

are infectious (streptodermia (photo 50, 52), necrotizing tonsillitis (photo 36), secondary tonsillitis (photo 54), peritonsilitis (photo 53) peritonsilar abscess (photo 55), otitis, purulent lymphadenitis, sepsis);

and allergic (rheumatism, myocarditis, arthritis, glomerulonephritis).

By the time of development:

early (first week of the disease);

late (2nd - 3rd week).

By the etiology:

specific or primary (caused by the same streptococcus);

secondary (caused by the other bacteria).








Peritonsilar abscess


Laboratory tests

1.                     The diagnose is confirmed by throat culture with group A b-hemolytic streptococcus.

2.                     Serology (antistreptolysin O, antidesoxyribonuclease B) with their grows in 2 weeks may be useful for documenting recent GABHS infection.

3.                     The complete blood cell count is helpful: usually white blood cell count higher 12500 cells/mm3, neutrophyllosis, left shift, eosynophylia, elevated ESR ECG, CBC and urinanalysis on the 10th day after the disease began, and on 21th day for possible late complications diagnostic (nephritis, myocarditis).

Diagnosis example:

Scarlet fever, typical form, exanthema period, severe (toxic) degree, complicated by the right side peritonsilar abscess.

Scarlet fever, typical form, recovery period, moderate degree, complicated by the myocarditis.


Differential diagnosis: tonsillitis may be seen with diphtheria, mononucleosis, adenovirus, and micoplasm; rashes may be seen with measles, rubella, and pseudotuberculosis.


Evidences for obligatory hospitalization of patients with infectious exanthema

1.                     The severe form of disease, when appears need in undertaking of intensive therapy; patients with moderate forms at age before 3 years.

2.                     Sick children from families with bad social-home conditions, especially in the event of impossibility of their isolation to prevent infections transmission.

3.                     Absence of conditions for examination and treatment at home.

4.                     Sick children from closed children institutions.

Advantages of the home treatment

1.                     Possibility of additional infection by hospital bacteria is completely excluded.

2.                     Realization of individual care principle for sick child is more full.

3.                     Avoiding stressful reactions, which could appear in case of hospital treatment.

Treatment in home conditions is possible

1.                     In conditions of isolated flat.

2.                     In case of satisfactory material position of the parents.

3.                     In case of parents desire to organize individual care and treatment at home.


1. Bed regime during an acute period.

2. Etiological treatment for scarlet fever is:

a. In the mild case penicillin orally (penicillin V) for 10 days 50,000-100,000 EU/kg/day divided in 3-4 doses. Erythromycin (or another macrolides) is alternative antibiotic (30-50 mg/kg/day). The course of treatment is 10 days.

b. In the moderate case penicillin intramuscularly (penicillin G), the same dose as in the mild case. The course of treatment is 10-14 days.

c. In the severe case: cefalosporins of the 1st-2nd generation, klindamycin, vancomycin intravenously for 10-14 days.

3. Detoxication therapy:

a. In the mild case large amount of oral fluids.

b. In the moderate and severe cases Glucose and saline solutions IV.

4. Antihistamines (in average doses) pipolphen, suprastin, claritin, cetirizin.

5. Medicine which strengthens vascular wall (vit. C and PP: ascorutin, galascorbin)

6. Control of fever (when the temperature is more than 38.5-39 C); in children before 2 mo and in case of perinatal CNS damage, seizures in the history, severe heart diseases when the temperature is up to 38 C with acetaminophen (paracetamol 10-15 mg/kg not often than every 4 hours (not more than 5 times per day) or ibuprophen 10 mg/kg per dose, not often than every 6 hours.

7. Local treatment with antiseptic fluids (gurgling), UV-insolation. Patient may go home from infection department not earlier the 10th day of the illness, in 10 days blood analysis, urinalyses, ECG must be done.


Prevention: isolation of the patient on the 10 days, but he mustnt visit school until 22 day of the disease. Contact person (children before 8 years) must be isolated for 7 days (period of incubation).



Infection due to Y. pseudotuberculosis is most often seen as a pseudoappendicitis syndrome without diarrhea.


ETIOLOGY. Y. pseudotuberculosis is differentiated biochemically from Y. enterocolitica on the basis of ornithine decarboxylase activity, fermentation of sucrose, sorbitol, cellobiose, and other tests, although some overlap between species may be seen. Antisera to somatic O antigens and sensitivity to yersinial phages may also be used to differentiate the two species. Subspecies-specific DNA sequences have been isolated that allow direct probe- and primer-specific differentiation of Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica.


EPIDEMIOLOGY. Less is known of the epidemiology of Y. pseudotuberculosis infections than for Y. enterocolitica or Y. pestis. The seasonal incidence in humans parallels that in wild and domestic animals. Transmission from cats and cat-contaminated substances is established. There is a low reported incidence in the 512-yr age range.


PATHOLOGY AND PATHOGENESIS. The pathology is similar to that described for Y. enterocolitica, with ileal and colonic mucosal ulceration and mesenteric adenitis. Necrotizing, epithelioid granulomas are seen in the mesenteric nodes. The appendix is frequently grossly and microscopically normal. Mesenteric nodes are frequently the only source of positive cultures. Y. pseudotuberculosis antigens bind directly to HLA class II molecules and function as superantigens, which may partly explain the clinical syndromes resembling Kawasaki syndrome caused by this organism.


CLINICAL MANIFESTATIONS. Children usually present with fever and abdominal pain that is diffuse or localized to the right lower quadrant. Frequently, there is tenderness over the McBurney point and strong clinical suspicion of appendicitis. At surgery, the terminal ileum is thickened and shiny with enlarged mesenteric nodes, which may appear necrotic. The appendix is normal or only mildy inflammed.



DIAGNOSIS. Mesenteric adenitis should be suspected in children with unexplained fever and abdominal pain. A characteristic picture of enlarged mesenteric lymph nodes, thickening of the terminal ileum, and no image of the appendix may appear on ultrasound. Y. pseudotuberculosis is rarely isolated. It is almost never isolated from stools, and the best source is an involved mesenteric node. Culture conditions are the same as for Y. enterocolitica.


Serologic tests have been described, but commercially available tests or standardized antigens are not available.


DIFFERENTIAL DIAGNOSIS. Appendicitis is the most common diagnosis. Inflammatory bowel disease and nonspecific intra-abdominal infections are also considered.


PREVENTION. Specific preventive measures other than avoiding exposure to potentially infected animals and careful food-handling practices are not apparent. Vaccines for prevention of Y. pseudotuberculosis have not been developed.


TREATMENT. Uncomplicated mesenteric adenitis due to Y. pseudotuberculosis is a self-limited disease, and antimicrobial therapy is not required. Culture-confirmed bacteremia should be treated with an aminoglycoside in combination with another agent, as for infections due to Y. enterocolitica.


Short statement of the material

Pseudotuberculosis is an acute infectious disease that is characterized by the expressed polymorphism of clinical symptoms with predominance of toxic-allergic syndrome, rashes like in scarlet fever, the damage of gastro-intestinal tract, liver; quite often has relapsed motion.


Etiology: Yersinia pseudotuberculosis, gram-negative bacillus



Source of infection-wild and home animals (rats, dogs, foxes, cats and other);

Way of transmitting alimentary;

Susceptible organism children (not infants), adults.



1. Entering the bacilli to gastrointestinal tract. An entrance gate is a thin bowel (terminal department and appendix)

2. Enteral phase: invasion of bacteria in enterocytes, development of local inflammation, diarrhea, enterotoxin secretion.

3. Regional lymphadenitis (regional infection).

4. Generalization (bacteriemia, toxemia) in severe cases.

5. Parenhymatous phase: hematogenous distribution of bacteria with forming of the secondary focus (lungs, liver, spleen, bones).

6. Immunological response, recovering from disease.

7. May be secondary bacteriemia (exacerbations and relapses), because of possible persistency in lymph nodes.


Clinical criteria

Incubation period is 3-18 days. Beginning is acute with high temperature, intoxication.

Polymorphism of complaints: malaise, fatigue, headache, sleepless, anorexia, arthralgias, muscle pain, sore throat, nausea, abdominal pain, dyspepsia.

Rashes: maculopapulous (like in scarlet fever), may be erythematosus or even erythema nodosum may developed (photo 56a, 56b);

- The eruption is characterized by dusky red, tiny papules;

- The rashes are present on face, intensified periorbitally, on the neck (glasses symptom, hood symptom (photo 56));

- On the body the rashes are intensified in skin folds (photo 57), at the sites of pressure (red dermographysm), on the hands, feet, (gloves,socks symptom), round the joints;

- The exanthema usually lasts 4 to 5 days and then begins to desquamate, first on the face, other parts of the body (photo 58) and last on the palms and soles (photo 59, 60).

Pharyngeal and tonsilar erythema without the exudates, erythema of the soft palate, conjunctivitis, corryza demonstrate catarrhal syndrome.

Strawberry tongue also simulates the scarlet fever (photo 61).

Abdominal syndrome; tenderness during the palpation of abdomen, may be acute appendicitis.

Dyspepsia: nausea, vomiting, liquid feces.

Hepatomegaly, rare splenomegaly, lymphadenopathy.

Arthritis of knees (photo 62), elbows, foot and hand small joints or arthralgia.

Hepatitis with or without the jaundice.

Toxic myocarditis.

Toxic nephritis, pyelonephritis.

Bronchitis or pneumonia may also develop.



hood symptom



Rashes are intensified in skin folds (Pastia lines)



socks symptom



Skin desquamation



Desquamation on palms



Desquamation on palms



Strawberry tongue





Nodular erythema in case of relapsed course


Clinical forms classification




Typical forms

Like Scarlet fever



Icteric (jaundice)


Generalized (septic)

Atypical forms







Indexes of severity:

Meningoencephalitic syndrome

Hemorrhagic syndrome

Considerable damage of liver

Abdominal syndrome

Damage of joints

Signs of process generalization



Uneven with exacerbations and relapses

Uneven with complications


Diagnosis example:

Pseudotuberculosis, typical combined (Scarlet fever like + arthralgic) form, moderate severity, uneven prolonged duration with exacerbation.


Features of pseudotuberculosis at the children of early age

high and prolong fever;

expressed hepatolienal syndrome;

systemic increase of lymphnodes;

dyspeptic syndrome;

damage of respiratory tract, development of pneumonia (very often);

rarely: scarlatina rashes, damage of joints;

prolong, undulating duration with exacerbation and relapses;

frequent complications.

Laboratory findings

Complete blood analyses: leucocytosis, neutrophilia with left shift, eosynophilia, ERS is enlarged.

Bacteriological: Yersinia Pseudotuberculosis may be found in feces, urine, blood and mucus.

Serologically: increasing of special antibodies 4 times and more in paired sera (AR, IHAR with diagnostic titles 1:200 and more).

Immune-enzyme analysis (ELISA test): Specific antibodies Ig M are positive in an acute phase of the disease.


Differential diagnosis should be performed among scarlet fever, measles, viral hepatitis, typhoid fever, paratyphoid fever, sepsis, enterovirus infection, bacterial diarrhea.




Scarlet fever

Infectious mononucleosis

Typhoid fever

Enterovirus infection

Viral hepatitis









Initial signs

Toxic, dyspeptic and different other


Sore throat, toxic

Lymphoproliferative, toxic


Catarrhal, toxic

Catarrhal, dyspeptic, arthralgic, asthenic


Pin-point, maculous-papulous, erythema

Pin-point, sand paper

maculous-papulous, erythema

Single reseals

Small maculous


(in case of B hepatitis)

Catarrhal sign






In the initial period

Changes in the throat

Hyperemia of the back pharyngeal wall


Tonsillitis Hyperemia of the back pharyngeal wall, posterior rhinitis

Hyperemia of the palatal arch, back pharyngeal wall



Joints damage

Arthritis, arthralgias

Not typical




Arthralgias in the initial period

Abdominal pain

Around the navel



In the right inguinal region

Around the navel

In the right hypochondria

Dyspeptic syndrome





Constipation, rare - diarrhea


More intensive in prodromal period



May be


May be






May be

Regional lymphadenitis


Hepato- and splenomegaly


Hepato-, rare - splenomegaly


Coated, strawberry from the 4th-5th day

Coated, strawberry from the 4th-5th day


Coated with grey,

teeth excavation on its borders



Damage of the nervous system

May be

Not typical

Not typical

Delirium, sopor

May be serous meningitis,



Hepatic encephalopathy in severe case



Children with mild form of pseudotuberculosis may be treated at home symptomatically without the etiological medicine.

Hospitalization is obvious for:

Children with moderate form of pseudotuberculosis;

Children with severe form of pseudotuberculosis.


half-bed regimen in mild cases;

bed regimen in moderate cases;

straight bed regimen in severe cases.


Icteric (jaundice) form N 5;

Abdominal (intestinal) form N 4;

Other forms N 15.



Chloramphenicol (orally) 10-15 mg/kg 3 or 4 times per day during all period of pyrexia

and plus 3 days (average duration is 14 days).

Alternative antibiotics (Reserve): cefalosporins of the 3rd or 4th generation (IM, IV),

In severe cases combination together with aminoglycosides of the 3rd generation (IM, IV).


Disintoxication: oral with large amount of alkaline fluids (in mild cases), or parenteral with glucose-saline solutions (in moderate, severe cases);

Glucocorticoids 1-3 mg/kg (in equivalent to prednisolone) as a short course 3-5 days (in severe cases), for 2-4 wks in case of myocarditis;

Control of fever and myalgia (when the temperature is more than 38.5-39 C); in children before 2 mo and in case of perinatal CNS damage, seizures in the history, severe heart diseases when the temperature is up to 38 C with acetaminophen (paracetamol 10-15 mg/kg not often than every 4 hours (not more than 5 times per day) or ibuprophen 10 mg/kg per dose, not often than every 6 hours;

Antihistamines (in average doses) pipolphen, suprastin, claritin, cetirizin;

NSAIDs in case of arthritis, carditis, nodular erythema (ibuprophen, aspirin, voltaren,

indomethacin in average doses).



1.                     Deratization, disinfection.

2.                     Right keeping of products.

3.                     Looking after people from the epidemic focus for 18 days with bacteriological investigation.


Kawasaki disease

Kawasaki disease (KD), also known as Kawasaki syndrome, lymph node syndrome and mucocutaneous lymph node syndrome, is an autoimmune disease in which the medium-sized blood vessels throughout the body become inflamed. It is largely seen in children under five years of age. It affects many organ systems, mainly those including the blood vessels, skin, mucous membranes and lymph nodes; however, its rare but most serious effect is on the heart where it can cause fatal coronary artery aneurysms in untreated children. Without treatment, mortality may approach 1%, usually within six weeks of onset. With treatment, the mortality rate is less than 0.01% in the U.S. There is often a pre-existing viral infection that may play a role in its pathogenesis. The conjunctivae and oral mucosa, along with the epidermis (skin), become erythematous (red and inflamed). Edema is often seen in the hands and feet and one or both of the cervical lymph nodes are often enlarged. Also, a remittent fever, often 40C (104F) or higher, is characteristic of the acute phase of the disease. In untreated children, the febrile period lasts on average approximately 10 days, but may range from five to 25 days. The disorder was first described in 1967 by Dr. Tomisaku Kawasaki in Japan


Kawasaki disease affects boys more than girls with people of Asian ethnicity, particularly Japanese and Korean people are most susceptible as well as people of Afro-Caribbean ethnicity. The disease was rare in Caucasians until the last few decades and incidence rate fluctuates from country to country.

Currently, Kawasaki disease is the most commonly diagnosed pediatric vasculitis in the world. By far the highest incidence of Kawasaki disease occurs in Japan, with the most recent study placing the attack rate at 218.6 per 100,000 children <5 years of age (~1 in 450 children). At this present attack rate, more than 1 in 150 children in Japan will develop Kawasaki disease during their lifetime.

However, its incidence in the United States is increasing. Kawasaki disease is predominantly a disease of young children, with 80% of patients younger than five years of age. Approximately 2,000-4,000 cases are identified in the United States each year.

In the United Kingdom, estimates of incidence rate vary because of the rarity of Kawasaki disease. However, Kawasaki disease is believed to affect fewer than 1 in every 25,000 people.[54] Incidence of the disease doubled from 1991 to 2000 however, with 4 cases in per 100,000 children in 1991 compared with a rise of 8 cases per 100,000 in 2000.


The disease was first reported by Dr. Tomisaku Kawasaki in a four-year-old child with a rash and fever at the Red Cross Hospital in Tokyo, Japan in January of 1961, and later published a report on 50 similar cases. Later Yamamoto and colleagues were persuade that there is definite cardiac involvement when they studied and reported 23 cases, of which 11(48%) patients had abnormalities detected by an electrocardiogram. It was not until 1974 that the first description of this disorder was published in the English language literature. in the year 1976 Melish et al., described the same illness in 16 children in Hawaii. Melish and Kawasaki had independently developed the same diagnostic criteria for the disorder, which are still used today to make the diagnosis of classic KS.

A question was raised whether the disease only started during the period between 1960 and 1970, but later a preserved heart of a 7 year old boy died in 1870 was examined and showed three aneurysms of the coronary arteries with clots, as well as pathologic changes consistent with KS. KS is now recognized worldwide. In the United States and other developed nations, it appears to have replaced acute rheumatic fever as the most common cause of acquired heart disease in children.



Systemic vasculitis is an inflammatory condition affecting both veins and arteries throughout the body, and is usually caused by a proliferation of cells associated with an immune response to a pathogen, or autoimmunity. Systemic vasculitides may be classified according to the type of cells involved in the proliferation, as well as the specific type of tissue damage occurring within the vein or arterial walls. Under this classification scheme for systemic vasculitis, Kawasaki disease is considered to be a necrotizing vasculitis (also called necrotizing angeititis), which may be identified histologically by the occurrence of necrosis (tissue death), fibrosis, and proliferation of cells associated with inflammation in the inner layer of the vascular wall. Other diseases featuring necrotizing vasculitis include Polyarteritis nodosa, Wegener's granulomatosis, Henoch-Schönlein purpura and Churg-Strauss syndrome. Kawasaki disease may be further classified as a medium-sized-vessel vasculitis, affecting medium and small sized blood vessels, such as the smaller cutaneous vasculature (veins and arteries in the skin) that range from 50 to 100m in diameter. KD is also considered to be a primary childhood vasculitis, a disorder associated with vasculitis that mainly affects children under the age of 18. A recent, consensus-based evaluation of vasculitides occurring primarily in children resulted in a classification scheme for these disorders, to both distinguish them and suggest a more concrete set of diagnostic criteria for each. Within this classification of childhood vasculitides, Kawasaki disease is, again, a predominantly medium-sized vessel vasculitis.

It is also an autoimmune form of vasculitis, and is not associated with ANCA antibodies, unlike other vasculitic disorders associated with them, such as wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. This categorization is considered essential for appropriate treatment.

Signs and symptoms



(A) Bilateral, non-exudative conjunctivitis with perilimbal sparing - "conjunctival injection".

(B) Strawberry tongue and bright red, swollen lips with vertical cracking and bleeding.

(C) Erythematous rash involving perineum.

(D) Erythema of the palms, which is often accompanied by painful, brawny edema of the dorsa of the hands.

(E) Erythema of the soles, and swelling dorsa of the feet. (F) Desquamation of the fingers.

(G) Erythema and induration at the site of a previous vaccination with Bacillus Calmette-Guérin (BCG).

(H) Perianal erythematous desquamation.

A child showing characteristic "strawberry tongue" seen in Kawasaki disease



Kawasaki disease often begins with a high and persistent fever that is not very responsive to normal treatment with paracetamol (acetaminophen) or ibuprofen. it is the most prominent symptom in Kawasaki disease, which is a characteristic sign of the acute phase of the disease, is normally high (above 39-40º C), remittent and followed by extreme irritability recent reports says it is even present in patients with atypical or incomplete KD, nevertheless recent reports says it is not present on 100% of cases. The first day of fever is considered the first day of illness, and the duration of fever is on average one to two weeks; in the absence of treatment, it may extend for three to four weeks, Prolonged fever is associated with higher incidence of cardiac involvement. It responds partially to antipyretic drugs and does not cease with the introduction of antibiotics. However, when appropriate therapy is started intravenous immunoglobulin (IVIG) and aspirin the fever is gone after two days.

Bilateral conjunctival injection was reported by many publications to be the most common symptom after fever, it typically involves the bulbar conjunctivae, is not accompanied by suppuration, it is not painful. It usually begins shortly after the onset of fever during the acute stage of the disease. Anterior uveitis may be present on slit-lamp examination. iritis can occur too.



Inflammation of the mucous membranes in the mouth, along with erythema (redness), edema (swelling) with fissures (cracks in the lip surface), desquamation (peeling) and exsudation of the lips are also evident.


The oropharynx mucosa has enanthema and the tongue maintains an unusual red appearance termed "strawberry tongue" (marked erythema with prominent gustative papillae).

Keratic precipitates (detectable by a slit lamp but usually too small to be seen by the unaided eye), and swollen lymph nodes may also be present and can be the first manifestation of the disease.

Rashes occur early in the disease, and the cutaneous rash observed in patients with KD is non-specific, polymorphic, non-itchy and normally observed up to the fifth day of fever. Cutaneous exanthema may comprise macular-papular erythematous and fissure lesions, the most common type, in addition to urticariform type rash, purpuric, multiform-like erythema. and peeling of the skin in the genital area, hands, and feet (especially around the nails and on the palms and soles) may occur in later phases.





Some of these symptoms may come and go during the course of the illness. It is a syndrome affecting multiple organ systems, and in the acute stage of KD, systemic inflammatory changes are evident in many organs.


Myocarditis, pericarditis, valvulitis, aseptic meningitis, pneumonitis, lymphadenitis, and hepatitis may be present and are manifested by the presence of inflammatory cells in the affected tissues. If left untreated, some symptoms will eventually relent, but coronary artery aneurysms will not improve, resulting in a significant risk of death or disability due to myocardial infarction (heart attack). If treated in a timely fashion, this risk can be mostly avoided and the course of illness cut short.




Diarrhea, abdominal pain, vomiting, liver dysfunction, pancreatitis, Hydrops gallbladder, cholangitis, intussusception, intestinal pseudo-obstruction, ascites, splenic infarction.


Polyarthritis and arthralgia.


Myocarditis, pericarditis, valvular heart disease.


Urethritis, prostatitis, cystitis, priapism, Interstitial nephritis, orchitis, nephrotic syndrome.


Aseptic meningitis, and sensorineural deafness.


Influenza-like illness, plural effusion, Atelectasis.


Erythema and induration at BCG vaccine site, Beau's lines, and finger gangrene.



Less common manifestations

  High-grade fever (greater than 39 C or 102 F; often as high as 40 C or 104 F), The duration of fever is on average one to two weeks; in the absence of treatment, it may extend for three to four weeks. However, when appropriate therapy is started the fever is gone after two days.

  Red eyes (conjunctivitis) bilateral without pus or drainage, also known as "conjunctival injection".

  Anterior uveitis.

  Bright red, chapped, or cracked lips.

  Red mucous membranes in the mouth.

  Strawberry tongue, white coating on the tongue or prominent red bumps (papillae) on the back of the tongue.

  Red palms of the hands and the soles of the feet.

  Peeling (desquamation) palms and soles (later in the illness); peeling may begin around the nails.

  Rash which may take many forms, non-specific, polymorphic, non-itchy, but not vesicle-bullous lesions, and appears on the trunk.

  Swollen lymph nodes (frequently only one lymph node is swollen, and is usually on one side), particularly in the neck area.

  Joint pain (arthralgia) and swelling, frequently symmetrical, Also arthritis can occur.


  Tachycardia (rapid heart beat).

  Beau's lines (transverse grooves on nails).

  May find breathing difficult.


X-ray showing aneurysmal enlargement of the coronary arteries, which is a complication in a Kawasaki syndrome


The cardiac complications are the most important aspect of the disease. Kawasaki disease can cause vasculitic changes (inflammation of blood vessels) in the coronary arteries and subsequent coronary artery aneurysms. These aneurysms can lead to myocardial infarction (heart attack) even in young children. Overall, about 1018% of children with Kawasaki disease develop coronary artery aneurysms with much higher prevalence among patients who are not treated early in the course of illness. Kawasaki disease and rheumatic fever are the most common causes of acquired heart disease among children in the United States.


Like all autoimmune diseases, the cause of Kawasaki disease is presumably the interaction of genetic and environmental factors, possibly including an infection. The specific cause is unknown, but current theories center primarily on immunological causes for the disease. Evidence increasingly points to an infectious etiology, but debate continues on whether the cause is a conventional antigenic substance or a superantigen. Children's Hospital Boston reported that "some studies have found associations between the occurrence of Kawasaki disease and recent exposure to carpet cleaning or residence near a body of stagnant water; however, cause and effect have not been established." Other data suggests possible correlation of KD with tropospheric wind patterns

An association has been identified with a SNP in the ITPKC gene, which codes an enzyme that negatively regulates T-cell activation. An additional factor that suggests genetic susceptibility is the fact that regardless of where they are living, Japanese children are more likely than other children to contract the disease. The HLA-B51 serotype has been found to be associated with endemic instances of the disease



Criteria for Diagnosis of Kawasaki Disease



Fever of ≥5 days' duration associated with at least 4 of the following 5 changes



Bilateral nonsuppurative conjunctivitis



One of more changes of the mucous membranes of the upper respiratory tract, including pharyngeal injection, dry fissured lips, injected lips, and "strawberry" tongue



One or more changes of the extremities, including peripheral erythema, peripheral edema, periungual desquamation, and generalized desquamation



Polymorphous rash, primarily truncal



Cervical lymphadenopathy >1.5 cm in diameter



Disease cannot be explained by some other known disease process

A diagnosis of Kawasaki disease can be made if fever and only 3 changes are present in conjunction with coronary artery disease documented by two-dimensional echocardiography or coronary angiography.


Source: Nelson's essentials of pediatrics


Kawasaki disease can only be diagnosed clinically (i.e. by medical signs and symptoms). There exists no specific laboratory test for this condition. It is difficult to establish the diagnosis, especially early in the course of the illness, and frequently children are not diagnosed until they have seen several health care providers. Many other serious illnesses can cause similar symptoms, and must be considered in the differential diagnosis, including scarlet fever, toxic shock syndrome, juvenile idiopathic arthritis, and childhood mercury poisoning (infantile acrodynia).

Classically, five days of fever plus four of five diagnostic criteria must be met in order to establish the diagnosis.

The criteria are: (1) erythema of the lips or oral cavity or cracking of the lips; (2) rash on the trunk; (3) swelling or erythema of the hands or feet; (4) red eyes (conjunctival injection) (5) swollen lymph node in the neck of at least 15 millimeters.





Many children, especially infants, eventually diagnosed with Kawasaki disease do not exhibit all of the above criteria. In fact, many experts now recommend treating for Kawasaki disease even if only three days of fever have passed and at least three diagnostic criteria are present, especially if other tests reveal abnormalities consistent with Kawasaki disease. In addition, the diagnosis can be made purely by the detection of coronary artery aneurysms in the proper clinical setting.


A physical examination will demonstrate many of the features listed above.

Blood tests

  Complete blood count (CBC) may reveal normocytic anemia and eventually thrombocytosis

  Erythrocyte sedimentation rate (ESR) will be elevated

  C-reactive protein (CRP) will be elevated

  Liver function tests may show evidence of hepatic inflammation and low serum albumin

Other optional tests

  Electrocardiogram may show evidence of ventricular dysfunction or, occasionally, arrhythmia due to myocarditis

  Echocardiogram may show subtle coronary artery changes or, later, true aneurysms.

  Ultrasound or computerized tomography may show hydrops (enlargement) of the gallbladder

  Urinalysis may show white blood cells and protein in the urine (pyuria and proteinuria) without evidence of bacterial growth

  Lumbar puncture may show evidence of aseptic meningitis

  Angiography was historically used to detect coronary artery aneurysms and remains the gold standard for their detection, but is rarely used today unless coronary artery aneurysms have already been detected by echocardiography.

  Temporal artery biopsy


Children with Kawasaki disease should be hospitalized and cared for by a physician who has experience with this disease. When in an academic medical center, care is often shared between pediatric cardiology and pediatric infectious disease specialists (although no specific infectious agent has been identified as yet).[38] It is imperative that treatment be started as soon as the diagnosis is made to prevent damage to the coronary arteries.

Intravenous immunoglobulin (IVIG) is the standard treatment for Kawasaki disease and is administered in high doses with marked improvement usually noted within 24 hours. If the fever does not respond, an additional dose may have to be considered. In rare cases, a third dose may be given to the child. IVIG by itself is most useful within the first seven days of onset of fever, in terms of preventing coronary artery aneurysm.

Salicylate therapy, particularly aspirin, remains an important part of the treatment (though questioned by some) but salicylates alone are not as effective as IVIG. Aspirin therapy is started at high doses until the fever subsides, and then is continued at a low dose when the patient returns home, usually for two months to prevent blood clots from forming. Except for Kawasaki disease and a few other indications, aspirin is otherwise normally not recommended for children due to its association with Reye's syndrome. Because children with Kawasaki disease will be taking aspirin for up to several months, vaccination against varicella and influenza is required, as these infections are most likely to cause Reye's syndrome.

Corticosteroids have also been used, especially when other treatments fail or symptoms recur, but in a randomized controlled trial, the addition of corticosteroid to immune globulin and aspirin did not improve outcome. Additionally, corticosteroid use in the setting of Kawasaki disease is associated with increased risk of coronary artery aneurysm, and so its use is generally contraindicated in this setting. In cases of kawasaki disease refractory to IVIG, cyclophosphamide and plasma exchange have been investigated as possible treatments, with variable outcomes.

There are also treatments for iritis and other eye symptoms. Another treatment may include the use of Infliximab (Remicade). Infliximab works by binding tumour necrosis factor alpha.[53]


With early treatment, rapid recovery from the acute symptoms can be expected and the risk of coronary artery aneurysms greatly reduced. Untreated, the acute symptoms of Kawasaki disease are self-limited (i.e. the patient will recover eventually), but the risk of coronary artery involvement is much greater. Overall, about 2% of patients die from complications of coronary vasculitis. Patients who have had Kawasaki disease should have an echocardiogram initially every few weeks, and then every one or two years to screen for progression of cardiac involvement.

It is also not uncommon that a relapse of symptoms may occur soon after initial treatment with IVIG. This usually requires re-hospitalization and re-treatment. Treatment with IVIG can cause allergic and non-allergic acute reactions, aseptic meningitis, fluid overload and, rarely, other serious reactions. Overall, life-threatening complications resulting from therapy for Kawasaki disease are exceedingly rare, especially compared with the risk of non-treatment. There is also evidence that Kawasaki disease produces altered lipid metabolism that persists beyond clinical resolution of the disease.



1.                     Manual of children's infectious diseases / O. Ye. Fedortsiv, I. L. Horishna, I. M. Horishniy. - TERNOPL : UKRMEDKNYHA, 2010. - 382 p. - ISBN 978-966-673-145-9

2.                     Manual of Childhood Infections: The Blue Book (Oxford Specialist Handbooks in Paediatrics) by Mike Sharland, Andrew Cant and al. Published by Oxford University Press Inc., New York, 2011 , p. 881 ISBN: 978-019-957-358-5.

3.                     Illustrated Textbook of Paediatrics, 4th Edition. Published by Lissauer & Clayden, 2012, p. 552 ISBN: 978-072-343-566-2.

4.                     Nelson Textbook of Pediatrics, 19th Edition Kliegman, Behrman. Published by Jenson & Stanton, 2011, 2608. ISBN: 978-080-892-420-3.

5.                     Oxford Textbook of Medicine: Infection by David Warrell, Timothy M. Cox, John Firth and Mili Estee Torok , Published by Wiley-Blackwell, 2012

6.                     http://www.merckmanuals.com/professional/index.html