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Year : 2020  |  Volume : 66  |  Issue : 2  |  Page : 65-66

Idiopathic CD4+ T lymphocytopenia: Still a long way to understand the disease

Former Director Institute of Immunohaematology (ICMR), Mumbai, Maharashtra, India

Date of Submission23-Oct-2019
Date of Decision15-Dec-2019
Date of Acceptance16-Dec-2019
Date of Web Publication01-Apr-2020

Correspondence Address:
K Ghosh
Former Director Institute of Immunohaematology (ICMR), Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpgm.JPGM_595_19

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How to cite this article:
Ghosh K. Idiopathic CD4+ T lymphocytopenia: Still a long way to understand the disease. J Postgrad Med 2020;66:65-6

How to cite this URL:
Ghosh K. Idiopathic CD4+ T lymphocytopenia: Still a long way to understand the disease. J Postgrad Med [serial online] 2020 [cited 2023 Jun 2];66:65-6. Available from:

In this issue of the journal, Shivaswamy[1]et al. describe a case of idiopathic CD4 positive T lymphocytopenia (ICL) with ulcerative colitis and Candida infection. The patient fulfilled all the US Centers for Disease Control and Prevention CDC criteria[2] for the diagnosis of ICL. This is a very rare condition[3] and is increasingly being picked up because of the widespread availability of flow cytometers in diagnostic laboratories.

HIV 1 and 2 infection is the commonest cause of CD4+ T lymphocytopenia as also human T cell leukemia virus type 1 (HTLV-1) and 2 infections. Many viral and rickettsial infections, as well as some of the autoimmune and malignant conditions, can cause CD4+ T lymphocytopenia. Drugs that suppress bone marrow or cause suppression of lymphocyte production or increase its destruction do the same. Various chemotherapies and radiotherapy can reduce peripheral T lymphocyte counts. However, many of these conditions are transient and may not reduce the CD4+ T cell count substantially. Hence the need by CDC for a CD4+ T cell count of less than 300/ul or less than 20% of total T cell count on more than one occasion separated by at least 6 weeks. As the commonest cause of persistently low CD4+ T cell count is HIV infection, hence, there are fears whether similar kind, yet unknown, viral infection can also cause this syndrome? Initially, some interest was generated by finding transmissible intracisternal retrovirus (Carnation Italian ringspot virus [CIRV]) as a possible cause for this syndrome[4] but subsequently, this study could not be duplicated.

A few cases of ICL has already been reported from India with various opportunistic infections.[5],[6] ICL affects both male and female patients. Though mostly it has been reported in patients between 30 and 60 years but children as well as elderly persons could also be affected.

How do we diagnose such cases? When the patient presents with unusual infections Cryptococcus meningitis, Pneumocystis jiroveci pneumonia, tuberculosis, nontuberculous mycobacterial infections, toxoplasmosis, leishmaniasis, Nocardia, John Cunningham (JC) virus infection, human papillomavirus infection, recurrent Candida, Histoplasma, herpes, and other unusual infections or recurrent infections, CD4 T cell count should be assessed. Lymphocytopenia with simple blood count may be a pointer for the presence of CD4+ lymphocytopenia.

Some patients may have associated autoimmune phenomenon or underlying malignancy but usually no antibody deficiency.[3],[7] A proportion of these patients also have additional CD8+ T cell deficiency or natural killer cell deficiency.

Is the CD4+ T lymphocytopenia in the patient persistent? In a majority of the cases, it is so but in a small minority CD4+ T cell counts recover over time.

What is the natural history of this condition?[3],[7],[8] These studies have reported that >80% of patients present with an unusual infection, 15–20% of them have autoimmune conditions mainly vasculitic illness, 20% develop various malignancies, and rest remain asymptomatic or even may recover, underlining the extreme heterogeneity of this condition.

Once the diagnosis is established, how do we manage such cases in our present-day understanding? Infections and secondary autoimmune disorders or malignancy need to be treated using standard protocols for each disorder. However, these patients need regular follow-up to find out spontaneous recovery and may need prophylactic cotrimoxazole and/or acyclovir, famciclovir administration. As Cryptococcus infection is extremely common in these patients, once the infection is diagnosed and treated subsequent suppressive treatment for the same needs to be continued indefinitely. Some of the patients show good improvement in CD4+ T lymphocyte count on a weekly injection of pegylated IL-2.[8]

Is there any special message related to this rare condition for Indian patients in India? India is a very populous country, hence, though rare in relative terms, such patients may be present in our country in large numbers and very few are probably diagnosed? Hence, doctors should be alert about this condition, particularly with those patients who present with AIDS-defining infections but are HIV negative.

Novel viral infection in a subset of these patients may be discovered if properly designed nationwide epidemiologic study is done with these patients. We collect more than 10 million blood units in different blood banks in this country. Many asymptomatic CD4+ T lymphocytopenia patients may be detected if these blood donors are targeted for such a study. Those who are interested in knowing more about the condition are referred to available reviews.[3],[7],[8]

 :: References Top

Umamaheshwari S, Sumana MN, Shetty MS, Gopal S. Idiopathic CD4+ T lymphocytopenia: A case report. J Post Grad Med 2020;66: 102-4.  Back to cited text no. 1
Centers for Disease Control (CDC). Unexplained CD4+ T-lymphocyte depletion in persons without evident HIV infection--United States. MMWR Morb Mortal Wkly Rep 1992;41:541-5.  Back to cited text no. 2
Regent A, Autran B, Carcelain G, Cheynier R, Terrier B, Charmeteau-DeMuylder B, et al.(French idiopathic CD4+ T cell lymphocytopenia study group) idiopathic CD4+ T lymphocytopenia. Medicine 2014;3:61-72.  Back to cited text no. 3
Gupta S, Ribak CE, Gollapudi S, Kim C-H, Salahuddin SZ. Detection of a human intracisternal retroviral particle associated with CD4+ T-cell deficiency. Proc Natl Acad Sci U S A 1992;89:7831-5.  Back to cited text no. 4
Nambirajan A, Suri V, Kataria V, Sharma MC, Goyal V. Progressive multifocal leukoencephalopathy in a 44-year old male with idiopathic CD4+ T-lymphocytopenia treated with mirtazapine and mefloquine. Neurol India 2017;65:1061-64.  Back to cited text no. 5
[PUBMED]  [Full text]  
Augustine R, Khalid M, Misri ZK, Hegde S. Idiopathic CD4+ T-lymphocytopenia—A diagnostic dilemma. J Assoc Physicians India 2010;58:45-7.  Back to cited text no. 6
Smith DK, Neal JJ, Holmberg SD, Centre for disease control idiopathic CD4+ T lymphocytopenia task force. Unexplainned opportunistic infections and CD4+ T lymphocytopenia without HIV infection: An investigation of cases in the United States. New Engl J Med 1993;328:373-9.  Back to cited text no. 7
Yarmohammadi H, Cunningham-Rundles C. Idiopathic CD4 lymphocytopenia: Pathogenesis, etiologies, clinical presentations and treatment strategies. Ann Allergy Asthma Immunol 2017;119:374-8.  Back to cited text no. 8


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