KAWASAKI DISEASE

Suppurative lymphadenitis REF: Harrison’s 17^th ed chapter 319

KAWASAKI DISEASE, also referred to as mucocutaneous lymph node syndrome, is an acute, febrile, multisystem disease of children. Some 80% of cases occur prior to the age of 5, with the peak incidence occurring at <2 years.

It is characterized by:

1. Nonsuppurative cervical adenitis
2. Changes in the skin and mucous membranes such as edema; congested conjunctivae; erythema of the oral cavity, lips, and palms
3. Desquamation of the skin of the fingertips.
4. Although the disease is generally benign and self-limited, it is associated with coronary artery aneurysms in 25% of cases, with an overall case-fatality rate of 0.5-2.8%. These complications usually occur between the third and fourth weeks of illness during the convalescent stage.
5. Vasculitis of the coronary arteries is seen in almost all the fatal cases that have been autopsied.
6. There is typical intimal proliferation and infiltration of the vessel wall with mononuclear cells. Beadlike aneurysms and thromboses may be seen along the artery. Other manifestations include pericarditis, myocarditis, myocardial ischemia and infarction, and cardiomegaly

Treatment of choice:

1. The prognosis of this disease for uneventful recovery is excellent.
2. High-dose IV globulin (2 g/kg as a single infusion over 10 h) together with aspirin (100 mg/kg per day for 14 days followed by 3-5 mg/kg per day for several weeks) for coronary complications.

Most common cause of vasculitis in children is Henoch Scholein Purpura (HSP) and not kawasaki disease.

The child is fully immunised which makes measles unlikely, no history of prior treatment with drugs so no chance for Steven Johnson, ASO normal so scarlet fever is unlikely.

The findings in this child are virtually diagnostic of Kawasaki disease. Diagnostic criteria for Kawasaki disease is fever for >/= 5 days + 4 of the following

Kawasaki disease is associated with bilateral non purulent conjunctival injection.

Pedal edema, Truncal rash and Pharyngeal congestion are all features of Kawasaki disease.

Ref: Nelson’s Book of Pediatrics 17th Edition, Page 824; Essential Pediatrics, O.P.Ghai, 6th edition, Chapter 21, Page 586.

Suppurative lymphadenopathy

Ans. is ‘c’ i.e., Thrombocytopenia

Kawasaki disease

o Kawasaki disease, also known as lymph node syndrome, mucocutaneous lymph node syndrome and infant polyarteritis, is a poorly understood self – limited vasculitis that affects many organs, including the skin, mucus membrane, lymph nodes, heart and blood vessel walls.

• It is usually seen in children younger than 5 years.

o Kawasaki disease predominantly affect medium sized vessels, but may also affect small or large vessels. Presentation

• Presenting features may be divided into ‑

I. Mucocutaneous, Lymphnode involvement

o Often begins with high grade fever

o Erythma of mouth, red cracked lips, a strawberry tongue.

o Bilateral conjuctival injection with iritis and keratic precipitate.

o Red palms and soles

o Rash, which may take many forms (but not vesicular), on trunk

o Rash with peeling of skin in genital area —> perinea] desquamation.

o Cervical lymphadenopathy

o Beau’s lines (transverse grooves on nails)

o Arthralgia

2. Heart

o The cardiac complications are the most important aspect of the disease.

o These are due to coronary vasculitis.

o Vasculitis causes coronary ectasia and coronary artery aneurysm.

o Aneurism may lead to MI and sudden death.

o Myocarditis, pericarditis with small pericardial effusion.

o Valvular regurgitation.

Laborator findings

o Elevated ESR                 o Normocytic anemia

o Elevated CRP                 o WBC count is normal or elevated with a predominant of neutrophils. o Thrombocytosis

Ans. is ‘a’ i.e., Thrombocytopenia

• In Kawasaki disease, there is thrombocytosis.

Ans. is ‘a’ i.e., Associated with coronary artery aneurysm in up to 25%

“Coronary artery aneurysm develop in up to 25% of untreated patients” – Nelson

Kawasaki disease

o Kawasaki disease, also known as lymph node syndrome, mucocutaneous-lymph node syndrome, and infant polyarteritis, is a poorly understood self-limited vasculitis that affects many organs, including the skin mucous membrane, lymph nodes, heart and blood vessel walls.

• It is usually seen in children younger than 5 years.
• Kawasaki disease predominantly affect medium sized vessels, but may also affect small or large vessels.

Presentation

• Presenting features may be divided into : ‑

1. Mucocutaneous, lymphnode involved

             Often begins with high grade fever.

             Erythma of mouth, red cracked lips, a strawberry tongue.

           Bilateral conjuctival injection with iritis and keratic precipitate.

                  Red palms and soles

           Rash, which may take many forms (but not vesicular), on trunk.

           Rash with peeling of skin in genital area perineal desquamation.

               Cervical lymphadenopathy

             Beau’s lines (transverse grooves on nails).

                                                                                            Arthralgia

2. Heart

           The cardiac complications are the most important aspect of the disease.

             These are due to coronary vasculitis.

           Vasculitis causes coronary ectasia and coronary artery aneurism.

             Aneurism may lead to MI and sudden death.

             Myocarditis, pericarditis with small pericardial effusion.

                  Valvular regurgitation

Laborator findings

Lymph node biopsy does not aid the diagnosis of Kawasaki disease (not used)

o The diagnosis of Kawasaki disease is based on presence of specific clinical signs (Clinical criteria). o These is no specific laboratory test

Ans. is ‘d’ i.e., Kawasaki disease

C. i.e. Kawasaki syndrome

Kawasaki mucocutaneous syndrome presents with fever (with spikes) for > 5 days, bilateral painless bulbar non discharging conjunctivitis, fissuring-crusting red lips, strawberry tongue, polymorphous erythematous eruption, desquamation-erythema & edema of extremity and acute non suppurative cervical lymphadenopathy^Q. Treatment of choice is intravenous gammaglobulinQ.

B i.e. Kawasaki disease; C i.e. Scarlet fever

Desquamation (scaling) is skin peeling or shedding of outermost layer of stratum corneum (normal turnover time is 27 dyas). Scarlet fever, staphylococcal scalded skin syndrome, SJS, TEN, toxic shock syndrome, exfoliative erythroderma, Kawasaki disease and DHS/DRESSQ lead to confluent desquamative erythemas.

Diseases associated with Fever and Rash

Centrally distributed maculopapular eruptions Acute meningococcemia, primary HIV infection

Drug induced hypersensitivity syndrome (DIHS)/ drug reaction with eosinophila and systemic symptoms (DRESS) l^stdisease /Rubeola/Measels (by paramyxovirusQ; cause Koplik’s spotQ)

3^rd disease/Rubella/German measles (by Toga virus; 1/ t Forschheimer spots) 5th disease/Erythema infectiosum (by human parvovirus B19; 1/t slapped cheeks appearance and gloves and socks syndromeQ) 6^th disease/Roseola/Exanthem subitum (by huma herpes virus 6)

Infectious mononucleosis (by Epstein barr virus)

– Drug induced and viral (Echo and coxsackieviruses) exanthemas

Epidemic typhus/Brill-Zinsser disease (by Rickettsia prowazeki)

Endemic (Murine) typus (by R. Typhi)

Rickettsial spotted fevers (by R. conori, Boutonneuse fever = R. australis = North Queensland tick typhus, R. Sibirica = Siberian tick typhus)

Human monocytotropic ehrlichiosis (by Ehrlichia chaffeensis)

Leptospirosis (by leptospira interrogans)

Lyme disease (Borrelia burgdoferiQ; lit erythema migrans and multiple secondary erythema migrans)

Southern tick associated rash illness/ STARI, Master’s disease (by Borrelia lonestari; IR smaller erythema migrans)

Typhoid fever (by salmonella typhi; l/t rose spotsQ on trunk)

Relapsing fever (Borrelia); Rat bite fecer/Sodoku (by spirillum minus)

Dengue fever (by Dengue-flaviviruses)

Rheumatic fever/Erythema marginatum (Group A streptococcus)Q

– SLE, Still’s disease (both autoimmune)

– African trypanosomiasis (Trypanosoma brucei rhodesiense/ gambiense)

– Arcanobacteria pharyngitis

(Corynebacterium/ arcanobacterium-hemolyticum)

Peripheral Erruptions

Chronic meningococcemia, disseminated gonococcal infections, human parvo virus B-19 infection

Secondary syphilis (T.pallidium), Bacterial endocarditis (strepto/staphylococcal etc).

Rocky mountain spotted fever (Rickettsia ricketsii)Q, Chikungunya fever (chikungunya virus),Hand-foot­and mouth disease (Coxsackievirus A16)Q

Rat bite fever/Haverhill fever (streptobacillus moniliformis)

Erythema multiforme (infection, drug etc.)

Confluent DesquamativeErthemas

2^.d disease/Scarlet fever Q (by group A streptococcus pyrogenic exotoxins A,B,C)

Toxic shock syndromeQ (by GAS pyrogenic exotoxin A/B or M; S.aureus toxic shock syndrome toxin 1, enterotoxin B or C)

Staphylococcal scalded skin syndrome (S. aureus phage group II)

Exfoliative erythroderma syndrome (underlying psoriasis, eczema, drug eruption, mycosis fungoides) DIHS/DRESS (aromatic anticonvulsants, minocycline, sulfonamides)

Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis =TEN (drugs e.g. allopurinol, anticonvulsant, antibiotics etc. in 80% cases; infection) Kawasaki diseaseQ (idiopathic)

Vesicobullous/Pustular Erruptions

– SSSS, TEN, DIHS/DRESS, Handfoot mouth Syndrome – Varicella/chicken pox (by varicella zoster virus; dewdrops on rose petal appearance)

– Hot tub folliculitis or hot foot syndrome (Pseudomonas aeruginosa)

– Variola/small pox (by variola major vivus)

– Primary HSV infection; disseminated herpes virus infection (VZV or HSV);

– Rickettsial pox (R. akari); Ecthyma gangrenosum (P.aeruginosa, other gram-ve rods, fungi)

– Acute generalized eruptive pustulosis (drugs, viral); disseminated vibrio vulnificus infection

Answer is D (Exudative conjunctivitis):

Kawasaki disease is associated with non exudative conjunctivitis

Diagnostic criteria for Kawasaki disease include bilateral bulbar conjunctival injection without exudate as one of their diagnostic criteria.

Classic Clinical criteria for Kawasaki Disease (Diagnosis is based on clinical signs)

Fever persisting at least 5 days

Presence of at least 4 principal features

• Changes in extremities

– Erythema of palms soles

– Edema of hands, feet

– Periungual peeling offingers,toes in weeks 2 and 3

• Polymorphous exanthem
• Bilateral bulbar conjunctival injection withoutexudate
• Changes in lips and oral cavity

– Erythema, lips cracking, strawberry tongue, diffuseinjection of oral and pharyngeal mucosa

• Cervical lymphadenopathy (>1.5cm diameter usually unilateral)
• Exclusion of other diseases with similar findings

Characteristic Laboratory Findings (There is no diagnostic test for KD)

• Leukocytosis with neutrophilia and immature forms
• Elevated erythrocyte sedimentation rate
• Elevated C- reactive protein (CRP)
• Anemia
• Abnormal plasma lipids
• Hypoalbuminemia
• Hypernatrenia
• Thrombocytosis after week 1
• Sterile pyuria
• Elevated serum transaminases 
• Elevated serum gamma glutamyl transpeptidase
• Pleocytosis of cerebrospinal fluid
  
• Leukocytosis in synovial fluid

Patients with fever at least 5 days and < 4 principal criteria can be diagnosed with Kawasaki disease when coronary artery abnormalities are detected with 2DE or angiography.

Answer is C (Thrombocytopenia):

Strong association has been reported between a novel form of S. aureus that release TSS toxin-1 & Kawasaki disease.( However, the disease is unresponsive to antibiotics.Q

Kawasaki disease is associated with thrombocytosis (not thrombocytopenia).

Answer is B (Thrombocytopenia):

Refer Kawasaki Disease Kawasaki disease is associated with thrombocytosis and not thrombocytopenia.

Answer is C (Thrombocytopenia) :

Kawasaki disease is associated with thrombocytosis and not thrombocytopenia. 

Answer is C (Thrombocytopenia) :

Kawasaki disease is associated with thrombocytosis and not thrombocytopenia.

Answer is A (Associated with coronary artery aneurysms in up to in 25% of untreated cases)

‘Coronary artery aneurysm develops in up to 25% of untreated patients’

The most common cause of vasculitis in children is Henoch Schonlein Purpura (HSP)

Although Ghai’s textbook mentions Kawasaki disease as the most common vasculitis in children, most other standard textbooks (Rudolph Pediatrics, Current Rheumatology Diagnosis and Treatment, CPDT etc) mention HSP as the most common vasculitis in children.

`HSP is the most common form of vasculitis in children’ – Current Rheumatology Diagnosis & Treatment (CRDT) /286 TISP is the most common vasculitis of childhood with an annual incidence of 15/100,000 children’

– Rudolph’s Fundamentals of Pediatrics 3^rd /284

Coronary artery aneurysms develop in up to 25% of untreated patients

(25% according to Nelson, 15-25% according to CPDT and 15-30% according to Ghai)

Coronary artery aneurysms are the most serious complication° seen in cases of Kawasaki disease

These are usually seen in the 2^nd or 3^rd week of illness (Rarely before day ten° (CPDT))

These are best detected by two dimensional echocardiography° (Nelson)

Lymph node biopsy does not aid the diagnosis of Kawasaki disease (Not used)

The diagnosis of Kawasaki disease is based on presence of specific clinical signs (clinical criteria) There is no specific laboratory test

The answer is A (Peak incidence at age > 5 years) :

80% of cases occur before the age of 5 years with a peak incidence of < 2 years.

• Kawasaki disease is an Acute febrile multisystem disease of children.
• Prolonged fever over 5 days that is unresponsive to antibiotics is seen.
• Although the disease is generally benign & self-limiting it is associated with coronary artery aneurysm in 25% of cases
• Non-suppurative cervical lymphadenopathy is characteristic

Answer is A (IV Immunoglobulins):

The treatment of choice in Kawasaki disease is intravenous immunglobulins

Answer is A (Immunoglobulins) :

The treatment of choice for Kawasaki disease is intravenous immunoglobulins

• Sign represented by an arrow shown in the photograph above represents Beau’s lines.
• Beau’s lines are deep grooved lines that run from side to side on the fingernail or the toenail. They may look like indentations or ridges in the nail plate. 
• Beau’s lines can also be seen one to two months after the onset of fever in children with Kawasaki disease.

Ans. is ‘a’ i.e., Kawasaki disease

• o Kawasaki disease is an acute, self limited vasculitis of unknown etiology that occurs predominantly in infants and young children of all races.
•  Coronary artery aneyrysms or ectasia develops in 15-25% of untreated children with the disease and may lead to ischemic heart disease, myocardial infarction, or even sudden death. In the USA, Kawasaki disease has surpassed acture rheumatic fever as teh leading cause of acquited heart disease in children

Ans. d. Kawasaki disease

Main visceral arteries and their branches
Kawasaki disease
– Arteritis with mucocutaneous lymph node syndrome; usually occurs in children.
Coronary arteries can be involved with aneurysm formation and/or thrombosis.