Extern ConferenceExtern Conference12 July 200712 July 2007

Chief Complaint : Fever with pustules at her both legs for 2 days

8-year-old Thai girl, from LOEI

1 mo. PTA, She had high grade fever for 2 days after swimming with her father in a pond

and developed few pustules at both legs.

She was admitted at Na-Duang hospital and received Ceftriaxone for 1 day, but clinical seem to be worse. Then, she was referred to Loei ho

spital.

History of present illness

Past history

• She had history of otitis media for 1 time and had recurrent oral ulcer once a week response

d to Kenalog for 1 year• No history of sinusitis, pneumonia, meningitis,

chronic diarrhea or skin abscess before this time

• Birth history : Term, NL, BW 3,400 gm, no perinatal complication, no delay detachment of

umbilical cord• No history of surgery and significant illness• Immunization : Complete EPI program, no

postvaccination complication• Allergies : no drugs or foods allergy

• Development : Appropriate growth. Doing well in 2nd grade

Past history

• She is 3rd child of family. • Her sister had history of recurrent otitis media about 5 times/yr, recurrent skin abscess that needed iv ATB and died from severe septicemia after ruptured appendicitis when

she was 14 yr-old.• Her brother had history of recurrent skin abscess in the sa

me way and died from severe septicemia at 10 months of age

• There is a consanguinity marriage in her parents.

Family history

PedigreePedigree

14 years 10 months 8 years

43 years 39 years

Physical examination at LOEI• V/S : T 39.4 ۫C BP 110/60 mmHg HR 160/min

RR 16/min• Wt 18.8 kg (P3-P10) Ht 119 cm (P10-P25) • GA : looked sick, mildly pale, no jaundice,

dyspnea, a skin lesions were pustules and blebs looked like Ecthyma gangrenosum• RS : fine crepitation both lungs

• Abdomen : soft, mild tender, liver just palpable, no splenomegaly

InvestigationCBC (5/6/50) :

Hb 10.7 g/dl, Hct 32%, MCV 63.6, MCH 19.5, Anisocytosis 1+, Hypochromic 1+, Microcytic 1+

WBC 18,600 (N68, Band19, L12)

Platelet 188,000/ul

UA (5/6/50) : WBC 1-2 RBC 0-1

Anti-HIV : Negative

Chest x-ray (7/6/50) : Consolidation at LLL could be due to bronchopneumonia with mild diffuse reticulonodular infiltration at both perihilar and

both basal lung

Investigation

Clinical course at LOEI• Rx : Cloxacillin and cefotaxime iv

2 days later, pustules were spread to all extremities.

• Ix : H/C and Pus C/S was identified as “Chromobacterium violaceum”.

Antibiotic was switched to Meropenem for 21 days. She responsed to treatment.

• Dx : Skin infection with pneumonia with severe gram negative septicemia

Post-treatmentSkin lesions

Chromobacterium violaceumChromobacterium violaceum

• Aerobic, gram-negative bacillus, catalase positive

• Epidemiology : Worldwide, rare infection

• Traumatic wound infection• Sepsis (mostly in

neutropenic patients and in patients with chronic granulomatous disease)

• Pneumonia after drowning

Purple-black colonies on blood agar plate

Chromobacterium violaceumChromobacterium violaceum

The patient was referred to Siriraj Hospital

Why?Why?

Problem List1. Severe skin infection with pneumonia and

sepsis from an unusual pathogen

2. Family history of recurrent severe skin infection

3. Consanguinity of parents

4. Recurrent oral ulcer

10 Warning signs of Primary Immune Deficiency

• 8 or more new ear infections in 1 yr• 2 or more serious sinus infections in 1 yr• 2 or more months on ATB with little effect• 2 or more pneumonias in 1 yr• Failure to gain weight or grow normally

• Recurrent, deep skin or organ abscesses• Persistent thrush in mouth/skin after 1 yr• Need for iv antibiotic to clear infections

• 2 or more deep-seated infection eg. meningitis, osteomyelitis, cellulitis or sepsis• Family history of primary immune deficiency

10 Warning signs of Primary Immune Deficiency

Immune Deficiency

• Primary immune deficiency – Genetic inheritant : X-linked, Autosomal

recessive, Autosomal dominant, Sporadic

• Secondary immune deficiency– Acquired eg. HIV, hematologic malignancy,

chemotherapy, immunosuppressive drugs, steroid use, Autoimmune diseases

Immune systemImmune system

1. Innate immunity – Non-specific, no

memory– eg. Phagocyte

(neurophils, monocyte, eosinophils), complement, skin, mucosal membrane

Immune systemImmune system

Innate immunityInnate immunity

• Phagocyte– recognize, engulf and

destroy pathogen esp. bacteria and fungus

– Killing mechanism via lysosomal enzymes (O2indenpendent)

or free radical

(O2 dependent)

Innate immunityInnate immunity• Complement : Group of proteins containing

of plasma proteins and membrane protein

2. Adaptive immunity– Specific, memory by Ag exposure

eg. Humoral immune system (B cell) from BM

Cellular immune system (T cell) from thymus

Immune system

Adaptive immunity

1. Humoral (Antibody-mediated) immune response– Antibodies are

produced by plasma cells (antigen-specific B lymphocyte)

2.Cellular (cell-mediated) immune response

– Mediated by antigen-specific cells called T lymphocyte via the antigen presenting cells

– Specific to intracellular pathogen eg. virus, higher bacteria and fungus

Adaptive immunity

What is primary immunodeficiency What is primary immunodeficiency ??

• Immune system is missing or doesn’t work correctly

• 1/10,000 to 1/100,000• Mostly inherited • very mild to serious form

Primary Immunodeficiency Diseases

• Divided in 4 functional compartments– The B-lymphocyte system– The T-lymphocyte system– The Phagocytic system– The Complement system

Epidermiology

Antibody 50 %

Phagocyte18 %

Cellular&Antibody20 %

Cellular10 %

Complement2 %

Stiehm, 4th ed, 1996

Characteristic T cell defect B cell defect Phagocyte defect Complement defect

Age of onset Early onset, 2-6 months

After maternal Ab diminish

Early onset Any age

Specific pathogens

Bacteria:

Mycobacteria

Virus: EBV, varicella, enterovirus

Fungus&parasite: candida, PCP

Bacteria:

Streptococcus

Staphylococcus

Haemophilus

Campylobactor

Virus:

Enterovirus

Fungus&parasite: giardia

cryptosporidia

Bacteria:

Staphylococcus

Pseudomonas

Serratia

Klebsiella

Fungus&parasite:

Candida, norcadia, aspergillus

Bacteria:

Neisseria

E.coli

Thomas A. Fleisher and Mark Ballow, Pediatric clinics of north america: December 2000

Characteristic T cell defect B cell defect Phagocyte defect Complement defect

Affected organs

FTT,

Protracted diarrhea,

Extensive mucocutaneous scandidiasis

Recurrent sinopulmonary infections,

Chronic GI symproms,

Malabsorption,

Arthritis,

Enteroviral meningoencephalitis

Skin:

dermatitis, impetigo, cellulitis

LN:

suppurative adenitis

Oral cavity:

Periodontotis

Ulcer

Internal organ abscess

osteomyelitis

Infection:

Meningitis

Arthritis

Septicemia

Recurrent sinopulmonary infections

Thomas A. Fleisher and Mark Ballow, Pediatric clinics of north america: December 2000

Characteristic T cell defect B cell defect Phagocyte defect

Complement defect

Special features

GVHD

Disseminated BCG or paralytic polio

Hypocalcemic tetany of infancy

Autoimmunity

Lymphoreticular malignancy

Lymphoma

Thymoma

Postvaccination paralytic polio

Prolonged attachment of umbilical cord

Poor wound healing

Rheumatoid arthritis

SLE

Vasculitis

Dermatomyositis

Scleroderma

Glomerulonephritis

angioedema

Thomas A. Fleisher and Mark Ballow, Pediatric clinics of north america: December 2000

Approach to this patient

• Differential diagnosis1. Phagocytic disorders

2. B-cell disorders

Phagocytic disorders• Skin abscess• Family history of recurrent severe skin

infection• Family history with consanguinity of parents

: CGD Autosomal recessive type• H/C and pus C/S : Chromobacterium

violaceum (atypical pathogen) common in CGD

Approach to this patient

Chronic granulomatous disease( CGD )

• The NBT test is based on microscopic evaluation of a limited number of cells. the NBT test may accumulate positive staining over time.

• DHR : a fluorescent assay using the conversion of dihydroxyrhodamine 123 (DHR) to rhodamine 123 not only diagnose CGD but also suggest the CGD genotype

Diagnosis of CGD

Investigation

Immunoglobulin level (5/7/50)

- IgG : 2,700 mg/dl (411-1435)

- IgA : 677 mg/dl (34-214)

- IgM : 203 mg/dl (15-115)

- IgE : <4.41 IU/ml (<90)

DHR (5/7/50) : Abnormal

DiagnosisDiagnosis

Primary immunodeficiency : Phagocytic disorder (Chronic granulomatous disease)

Management• Treat infection• Antibiotic prophylaxis• Avoid infection• Counseling• Specific treatment

– Bone marrow transplant– Gene therapy

Management in this patient• Antibiotic prophylaxis

– Cotrimoxazole (80/400) 1 tab oral pc morning, ½ tab oral pc evening

– Itraconazole (100) 1 tab oral OD morning

• Refer to Loei hospital for U/S abdomen

Take Home MessageAwareness about the patient that have

1. Recurrent infection

2. Uncommon organism

3. Increased dependency on ATB

4. Family history of severe infection

“10 Warning sign of 1o Immune Deficency”

Thank you for your attention