Dr.Ghaniya KC , Dr.Sajitha Nair , Dr.Sathyajit Nair , Dr Sindhu , Dr.Sreya , Dr.C.Jayakumar
Aims Kochi
Four year old male 2nd of NCM, had recurrent lower respiratory infections from 6 months of age
All together he had 8 admissions and of this 2 were in ICU with severe LV dysfunction
He had 2 episodes of bilateral CSOM from 6 months of age and now admitted for evaluation of high grade, intermittent fever and pain with bloody purulent discharge from both ears of 3 days duration .
H/O loose stools/cough/ breathing difficulty/oral candidiasis were negative
Birth history was normal and the cord fell on 5th day
He was asymptomatic for the first 6 months of life and was vaccinated as per the national schedule
At 6 months of age he had an episode of severe pneumonia
At1year and 2months he had another pneumonia and that ended up in septicaemia , myocarditis with severe LV dysfunction and deep vein thrombosis
CT Abdomen & Pelvis takes at this time showed- Hepatomegaly with periportal edema mild to moderate ascites and diffuse mesentric fat stranding.l,Left lung basal parenchymal opacity – possibly consolidation.
ECHO done showed structurally normal heart with normal coronaries.
In2020 child had COVID infection which was managed at home
Pneumonia recurred at Three year and One month ,3 year,5th month at 8th month 10th month and at 4 years
Gene expert forMTB,IGRA were-negative *
At 4 years 3 months he had B/L ASOM / Bronchopneumonia and at this juncture noted to have neutropenia
USG chest – No evidence of pleural effusion. HRCT Chest : consolidatory changes in both lungs. Atelectatic band noted in lower lobe of lung There is history of 2 childhood deaths in family
CLINICAL EXAMINATION :
At admission, this thriving child was Febrile Other vitals and PICCLE were normal
He had no BCG scar.Bilateral Tragal tenderness and purulent blood stained discharge present in the right ear.
Tonsil was small
Rest of the systemic examination including Respiratory system was normal
Lab TC – 5.96 ANC – 476,ALC – 4165,Hb – 10.7 g/dlPlt – 510 K/uL
Peripheral smear – Microcytic Hypochromic anemia with Severe neutropenia.
*Chest X-ray – no parenchymal infiltrates,no hilar adenopathy
*Serum Immunoglobulin profile: IgG <30.0 mg/dl Reference range : (463 -1236 mg/dL)
IgA <5.0 mg/dl Reference range : (25-154 mg/dL)
IgM <5.0 mg/dl Reference range : (43-196 mg/dL)
IgE 0.485 IU/ml Reference range : 1.07-68.9 IU/mL
*Basic Lymphocyte Panel – Decrease in the percentage and absolute count of CD19+ B lymphocytes. 1 %
*NBT-DHR – normal
*Ear Culture – Sterile
*Blood Culture – Sterile
*Reapeat USG Abdomen – Normal size
*ECHO-Structurally normal heart Biventricular function normal, EF : 76%
*Whole exon sequence awaited
As this boy had recurrent LRTI needing 8 hospital admissions with bilateral CSOM and small tonsils, a possibility of Primary Immunodeficiency Xlinked agammaglobulinemia was made
Child was given IVIG @ 400mg/kg.As he persisted to have neutropenia,he was given GCSF
His neutrophil counts improved with Inj Grafeel for 2 days.. Parents were counselled about the need to supplement IVIG after 4 weeks
X-linked agammaglobulinemia or Brutons agammaglobulinemia (XLA) is one of the most common pediatric primary immunodeficiencies that requires lifelong immunoglobulin replacement therapy for survival.
Molecular basis
Disruption in B cell development due to mutation in Bruton’s tyrosine kinase (Btk). This prevents precursor B cells in the bone marrow from forming mature, circulating B-lymphocytes and antibody-producing plasma cells in tonsils and lymph nodes leading to low, undetectable levels of all immunoglobulin isotypes .
So XLA patients are rendered vulnerable to invasive infections from encapsulated bacteria have ,enterovirus infections and Giardia lamblia
XLA patients commonly present with recurrent upper respiratory tract infections, sinusitis and otitis media, after 6 to 9 months
However, hospitalization for bacterial pneumonia, prompts the diagnostic work-up for immune deficiency disease.
Almost all cases of XLA get diagnosed before 5 years of age.
Even though there is no cure early management with immunoglobulin replacement therapy and antibiotics to prevent and treat infections prolong life expectancy
Any significant delay in diagnosis poses the danger of developing chronic, treatment-resistant infections, and end-organ damage that cannot be corrected.
There were experimental case series of Stem cell transplantation in Brutons ,but the results are not that optimum
Take home message
Suspect and investigate immuno deficiency in all unusual and recurrent infections at unusual sites ,fungal infections and failure to thrive