Idiopathic CD4+T cell lymphocytopenia: A rare immunodeficiency disorder

Introduction Idiopathic CD4+T cell lymphocytopenia (ICL), a rare immunodeficiency disorder, is a heterogeneous clinical syndrome with the universal finding of persistent CD4+ T-lymphocyte depletion, in the absence of human immunodeficiency virus (HIV) 1 or 2 infection or other known causes of immunodeficiency. It was first described by Centers for Disease Control (CDC) in 1992 in individuals who suffered from recurrent opportunistic infections and persistently low CD4 counts but HIV serology was repetitively negative. Most of the ICL patients originally reported were adults; however the disease has subsequently been described in a small number of children and adolescents. The patients usually present with recurrent episodes of opportunistic infections like mycobacteria, candida, bacterial pneumonia and disseminated viral infections. We report a boy who presented with features compatible with ICL.


Introduction
Idiopathic CD4+T cell lymphocytopenia (ICL), a rare immunodeficiency disorder, is a heterogeneous clinical syndrome with the universal finding of persistent CD4+ T-lymphocyte depletion, in the absence of human immunodeficiency virus (HIV) 1 or 2 infection or other known causes of immunodeficiency 1,2 .It was first described by Centers for Disease Control (CDC) in 1992 in individuals who suffered from recurrent opportunistic infections and persistently low CD4 counts but HIV serology was repetitively negative.Most of the ICL patients originally reported were adults; however the disease has subsequently been described in a small number of children and adolescents.The patients usually present with recurrent episodes of opportunistic infections like mycobacteria, candida, bacterial pneumonia and disseminated viral infections.We report a boy who presented with features compatible with ICL.

Case report
A 4 year 6 month old boy presented with recurrent episodes of cough, fever, loose stools, skin infections, ear discharge and oral thrush since the age of one month and history of four hospitalisations.At the age of one month he suffered from bacterial pneumonia, at 22 months post measles bronchopneumonia and at 3 years he had fever and convulsions with obtundation, followed by right sided hemiparesis.There was no history of intake of any immunosuppressants or immune-modifying drugs.Family members were healthy.
Bronchoalveolar lavage revealed M. tuberculosis.He was started on 4 drugs, isoniazid, rifampicin, pyrazinamide and ethambutol (HRZE) and the fever subsided after a few days.Owing to the disseminated nature and immunodeficiency, the plan of anti-TB drugs (ATD) was made as 2HRZE+10HR.On follow up over the next 12 months he remained apparently well though intermittent breakthrough fever occurred.

Discussion
Idiopathic CD4 T cell lymphocytopenia (ICL) is a very rare immunodeficiency disorder with fewer than 50 paediatric cases reported throughout the world 2 .The definition of ICL in children includes the following criteria 2 : 1.A CD4+T cell count of less than 1000 cells per cu mm in children 0 to 23 months of age and of less than 300 cells per cu mm in children 2 to 12 years of age, or a CD4+T lymphocyte count that is less than 20% of total lymphocytes on at least two separate measurements.
2. No serological evidence of infection on HIV testing (even if the child's mother is HIV seropositive).
3. Absence of any defined immunodeficiency or therapy associated with T cell depletion.
Our index case had a CD4 cell count less than 300 on 2 different occasions with absence of HIV seropositivity.
aetiology of ICL is currently unknown.Research has focused on identifying abnormalities in various aspects of immune function and the role of any possible triggering viral agents 3 .
The mechanism of CD4 cell loss in ICL appears to be due to spontaneous and accelerated CD4+ cell apoptosis (programmed cell death) in patients with advanced immune suppression and opportunistic infections 4 .Recent views on potential mechanism for CD4 depletion include overexpression of Fas / Fas ligand leading to apoptosis 5 , defective cytokine production, regenerative failure of haematopoietic stem cells, impaired thymic T cell maturation and autoantibody against CD4 cells.Opportunistic infections occur when the absolute CD4 cell count drops below 200 cells/cu mm.Conditions most commonly associated are mycobacterial infections, fungal infections (candida, cryptococcus, aspergillus, histoplasma) and viral infections (human papilloma virus, varicella, cytomegalovirus, Epstein-Barr virus, John Cunningham virus).Our index case suffered from mycobacterial and fungal infections.Recurrent bacterial infections are rare but are seen in children.Allergic conditions such as atopic dermatitis have often been linked to ICL 6 .Aside from persistently low CD4+ T cell counts, laboratory findings in ICL are variable.
There is no standard treatment for ICL, except for management of the associated conditions and the prompt treatment of infections.Emphasis should be on prevention of infection with antibiotic and antifungal prophylaxis.Some novel approaches like allogenic bone marrow transplantation, IL-2 administration have been tried in adult patients, but their use in children is limited.