hyper - immunoglobulin m syndrome ( higm ) is a rare heterogeneous group of disorders , 70% of which are due to cd40-ligand deficiency .
these patients are susceptible to recurrent sinopulmonary infections and opportunistic infections , especially pneumocystis jiroveci pneumonia .
bronchiectasis is characterized by abnormal dilated thick - walled bronchi that are inflamed and colonized by bacteria . after excluding cystic fibrosis , tuberculosis and congenital lung abnormalities
on searching the literature for the youngest and only case of higm with bronchiectasis , we could found data of a 7-year - old girl published by montella et al . to the best of our knowledge ,
the case described here is the youngest case of higm-1 presenting with bronchiectasis and , possibly , pj pneumonia .
a 5-year - old boy , born of consanguineous ( 4 degree ) marriage , presented with complaints of productive cough and right ear discharge since 1 year , fever and respiratory distress for 25 days and oral thrush since 20 days .
he had a history of five admissions in various hospitals for pneumonia since the age of 1 year .
he also had a history of repeated diarrhea ( six to seven episodes every year ) since the age of 6 months .
antitubercular therapy was given on an empirical basis at the age of 2.5 years , without any significant improvement .
two of his elder male siblings died because of recurrent pneumonia and diarrhea at the age of 2 years and 8 years .
onset of recurrent pneumonia and diarrhea in both the siblings was at about 8 months of age . on examination , his heart rate was 120/min , respiratory rate was 66/min , spo2 was 91% ( on room air ) and grade 2 clubbing was present .
right side maxillary area tenderness and right ear discharge ( yellowish - green ) were also noted .
his blood counts revealed total leukocyte count -27,000/cc ( p75 ) and the platelet counts and erythrocyte sedimentation rate were normal .
arterial blood gas revealed ph -7.32 , pco2 -53.1 mmhg , pao2 -60 mmhg and hco3 -26.9
liver function test , renal function tests and coagulation profile were normal . the serum lactate dehydrogenase level ( ldh ) was raised .
on bronchoscopy , the right bronchial tree showed collapse of some sub - segmental bronchi and proximal bronchiectasis .
high serum igm level and no detectable serum levels of igg and iga [ table 1 ] suggested higm syndrome .
his whole blood flow cytometry revealed reduced expression of cd40l ( cd154 ) on activated t lymphocytes after stimulation [ table 1 ] thus confirming the diagnosis of higm-1 .
chest roentgenogram performed 1 month before the admission and at the time of admission showed persistent opacity in the right middle zone .
high - resolution computed tomography ( hrct ) of the chest demonstrated bronchiectatic changes in the right lower lobe , right middle lobe , left lower lobe and lingular lobe [ figure 1a and b ] .
( a ) areas of ground - glass haze and nodular air space lesions in a branching pattern ( tree in bud ) in the right lower lobe , dilated and thickened bronchi in the left lower lobe , lingular lobe and right middle lobe .
( b ) ground - glass haze in the right lung with air space lesions in the right lower lobe the patient presented with severe respiratory distress , for which he was put on mechanical ventilation .
intravenous ( iv ) ceftriaxone and cloxacillin were started in addition to nebulizations with 3% saline and chest physiotherapy . on the basis of culture sensitivity ( pseudomonas growth )
iv liposomal amphotericin b and co - trimoxazole was given in view of probable invasive candidiasis and pj pneumonia , respectively .
he did respond to the treatment well , and was discharged in satisfactory condition and is in regular follow - up .
he is getting oral co - trimoxazole prophylaxis , ivig therapy ( 600 mg / kg ever 4 weeks ) , salbutamol and budesonide inhalation with mdi and spacer and 3% saline nebulization followed by chest physiotherapy at home .
x - linked higm syndrome results due to defects in class switch recombination caused by mutations in the cd40 ligand and nuclear factor kb essential modifier ( nemo ) .
t cell functions are also affected in both cd40l and nemo deficiency , which explains the associated opportunistic infections .
nemo gene defect was ruled out in our case due to the absence of ectodermal dysplasia , mycobacterial infection , osteopetrosis and lymphedema .
higm-1 usually presents around 6 - 9 months of age ( when maternal antibodies decrease below the protective level ) with recurrent sinopulmonary bacterial infections , opportunistic infections and recurrent diarrhea .
management of bronchiectasis includes antibiotics , bronchodilators , inhaled steroids , mucolytics and chest physiotherapy , along with treatment of underlying disorder .
the goal of therapy is to mobilize secretions and to reduce the infectious and inflammatory load , thereby preventing progression of airway destruction .
pj pneumonia is being reported as the presenting feature in about 40% of higm-1 patents .
festic et al . reported elevated ldh in 29 of 30 patients with non - hiv pj pneumonia .
the classic presentation of pcp is a bilateral interstitial pattern , which may be characterized as finely granular , reticular or ground - glass opacities . in the described patient ,
there was markedly elevated serum ldh level with ground - glass haze on contrast - enhanced computed tomography of the chest [ figure 1a and b ] , suggesting interstitial pneumonitis and hypoxemia suggesting possibility of pj pneumonia .
however ; we could not recover pj trophozoites and cysts in the bronchoalveolar lavage , which may be explained by the fact that bal ( bronchoalveolar lavage ) could only be performed after initial stabilization of the patient and co - trimoxazole was started empirically on the basis of raised ldh level with pneumonia and hypoxemia .
appropriate treatment of infections and regular ivig therapy ( every 3 - 4 weeks ) is considered the mainstay of therapy .
boiled drinking water to prevent cryptosporidium infection and co - trimoxazole prophylaxis to prevent pj pneumonia should be given .
the only curative treatment currently available for higm-1 is allogeneic hematopoietic cell transplantation ( hct ) .
early diagnosis and appropriate management of recurrent / persistent pneumonia in cases of higm-1syndrome may prevent development of bronchiectasis , a serious complication that limits the success of bone marrow transplantation , a definite cure of higm-1 syndrome .
 the x - linked hyper - immunoglobulin m syndrome ( higm-1 ) is a rare genetic disorder characterized by elevated serum igm levels and low to undetectable levels of serum igg , iga and ige . 
 these patients characteristically present with recurrent sinopulmonary infections and recurrent diarrhea . 
 they also have high susceptibility for pneumocystis jiroveci ( pj ) pneumonia . 
 herein , we report a case of hgm-1 in a 5-year - old boy who presented with bronchiectasis and , possibly , pj pneumonia . 
 the diagnosis was established on the basis of clinical features , immune profile , whole blood flow cytometry and history of two male sibling 's death due to recurrent pneumonia and diarrhea . 
INTRODUCTION
CASE REPORT
DISCUSSION