Idiopathic CD4+ lymphocytopenia

Idiopathic CD4+ lymphocytopenia (ICL) is a very rarecite journal
author=Walker UA, Warnatz K
title=Idiopathic CD4 lymphocytopenia
journal=Curr Opin Rheumatol
volume=18
issue=4
pages=389–95
year=2006
month=July
pmid=16763460
doi=10.1097/01.bor.0000231908.57913.2f
url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00002281-200607000-00012] medical syndrome. In this condition, the body has too few CD4+ T lymphocytes, which are a kind of white blood cell. It is sometimes called HIV-negative AIDS by patients and AIDS denialists.

People with ICL have a weakened immune system and are susceptible to opportunistic infections, although the rate of infections is lower than in people with AIDS.cite journal
author=Wladis EJ, Kapila R, Chu DS
title=Idiopathic CD4+ lymphocytopenia and Sjogren syndrome
journal=Arch. Ophthalmol.
volume=123
issue=7
pages=1012
year=2005
month=July
pmid=16009850
doi=10.1001/archopht.123.7.1012-a
url=http://archopht.ama-assn.org/cgi/reprint/123/7/1012-a.pdf]

Cause

The cause of ICL, like all idiopathic conditions, is unknown. It does not appear to be caused by a transmissible agent, such as a virus. [ [http://www.online-medical-dictionary.org/T-Lymphocytopenia,+CD4+.asp?q=T-Lymphocytopenia%2C+CD4%2B Online Medical Dictionary entry on T-lymphocytopenia] ] It is widely believed that that there is more than one cause.cite journal
author=Duncan RA, von Reyn CF, Alliegro GM, Toossi Z, Sugar AM, Levitz SM
title=Idiopathic CD4+ T-lymphocytopenia--four patients with opportunistic infections and no evidence of HIV infection
journal=N. Engl. J. Med.
volume=328
issue=6
pages=393–8
year=1993
month=February
pmid=8093636
doi=
url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=8093636&promo=ONFLNS19]

Diagnosis

The mandatory criteria for diagnosis of idiopathic CD4+ lymphocytopenia include: [UpToDate article on "Techniques and interpretation of measurement of the CD4 cell count in HIV-infected patients", by John G. Bartlett. Accessed 30 Oct 2006.]
*Low numbers of CD4+ cells, on two or more measurements over at least six weeks:
**CD4 cell count less than 300 cells per microliter, or
**Less than 20% of T lymphocytes are CD4+
*Lack of laboratory evidence of HIV infection
*Absence of any alternative explanation for the CD4 lymphocytopenia

A one-time finding of low CD4+ cells is usually associated with a recent infection and resolves on its own.

Alternative explanations for the low CD4 counts include conditions such as blood cancers (aleukemia), treatment with chemotherapy, immunosuppressive medications, or other medications that suppress or kill T cells, infections, and problems with blood production.cite journal
author=Busse PJ, Cunningham-Rundles C
title=Primary leptomeningeal lymphoma in a patient with concomitant CD4+ lymphocytopenia
journal=Ann. Allergy Asthma Immunol.
volume=88
issue=3
pages=339–42
year=2002
month=March
pmid=11926631
doi=
url=]

All criteria must be fulfilled for a diagnosis of ICL. Additionally, if these findings are present, but combined with other significant findings, such as anemia or thrombocytopenia, then other diagnoses must be considered.

Pathophyisology

The loss of CD4+ T cells appears to be through apoptosis.cite journal
author=Laurence J, Mitra D, Steiner M, Lynch DH, Siegal FP, Staiano-Coico L
title=Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia
journal=J. Clin. Invest.
volume=97
issue=3
pages=672–80
year=1996
month=February
pmid=8609222
pmc=507103
doi=10.1172/JCI118464
url=http://dx.doi.org/10.1172/JCI118464] The accelerated deaths of the T cells is likely driven by crosslinking T cell receptors.

Prognosis

In contrast to the CD4 cell depletion caused by HIV, patients with idiopathic CD4 lymphocytopenia generally have a good prognosis. [cite journal
author = Laurence J, Siegal F, Schattner E, Gelman I, Morse S | title = Acquired immunodeficiency without evidence of infection with human immunodeficiency virus types 1 and 2. | journal = Lancet | volume = 340 | issue = 8814 | pages = 273–4 | year = 1992 | pmid = 1353194 | doi = 10.1016/0140-6736(92)92359-N] [cite journal
author = Ho D, Cao Y, Zhu T, Farthing C, Wang N, Gu G, Schooley R, Daar E | title = Idiopathic CD4+ T-lymphocytopenia--immunodeficiency without evidence of HIV infection. | journal = N Engl J Med | volume = 328 | issue = 6 | pages = 380–5 | year = 1993 | pmid = 8093634 | doi = 10.1056/NEJM199302113280602] [cite journal
author = Spira T, Jones B, Nicholson J, Lal R, Rowe T, Mawle A, Lauter C, Shulman J, Monson R | title = Idiopathic CD4+ T-lymphocytopenia--an analysis of five patients with unexplained opportunistic infections. | journal = N Engl J Med | volume = 328 | issue = 6 | pages = 386–92 | year = 1993 | pmid = 8093635 | doi = 10.1056/NEJM199302113280603] The major risk to people with ICL is unexpected infections, including cryptococcus, atypical mycobacterial and Pneumocystis jiroveci pneumonia (PCP). The condition may also resolve on its own.cite journal
author=Zonios DI, Falloon J, Bennett JE, "et al"
title=Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors
journal=Blood
volume=112
issue=2
pages=287-294
year=2008
month=July
pmid=18456875
doi=10.1182/blood-2007-12-127878
url=http://bloodjournal.hematologylibrary.org/cgi/content/full/112/2/287]

ICL sometimes precedes and may be the first signal of several blood cancers. ICL patients have developed primary effusion lymphomacite journal
author=Niino D, Tsukasaki K, Torii K, "et al"
title=Human herpes virus 8-negative primary effusion lymphoma with BCL6 rearrangement in a patient with idiopathic CD4 positive T-lymphocytopenia
journal=Haematologica
volume=93
issue=1
pages=e21–3
year=2008
month=January
pmid=18166773
doi=10.3324/haematol.12085
url=http://www.haematologica.org/cgi/pmidlookup?view=long&pmid=18166773] cite journal
author=Richetta A, Amoruso GF, Ascoli V, "et al"
title=PEL, Kaposi's sarcoma HHV8+ and idiopathic T-lymphocitopenia CD4+
journal=Clin Ter
volume=158
issue=2
pages=151–5
year=2007
pmid=17566517
doi=
url=] , primary leptomeningeal lymphoma, diffuse large cell lymphoma,cite journal
author=Campbell JK, Prince HM, Juneja SK, Seymour JF, Slavin M
title=Diffuse large cell lymphoma and t(8;22) (q24;q11) in a patient with idiopathic CD4+ T-lymphopenia
journal=Leuk. Lymphoma
volume=41
issue=3-4
pages=421–3
year=2001
month=April
pmid=11378556
doi=
url=] MALT lymphoma,cite journal
author=Longo F, Hébuterne X, Michiels JF, Maniere A, Caroli-Bosc FX, Rampal P
title= [Multifocal MALT lymphoma and acute cytomegalovirus gastritis revealing CD4 lymphopenia without HIV infection]
language=French
journal=Gastroenterol. Clin. Biol.
volume=23
issue=1
pages=132–6
year=1999
month=January
pmid=10219614
doi=
url=] and Burkitt's lymphoma,cite journal
author=Shimano S, Murata N, Tsuchiya J
title= [Idiopathic CD4+ T-lymphocytopenia terminating in Burkitt's lymphoma]
language=Japanese
journal=Rinsho Ketsueki
volume=38
issue=7
pages=599–603
year=1997
month=July
pmid=9267164
doi=
url=] among others.

ICL may indirectly trigger autoimmune diseases. It has been associated with several cases of autoimmune disease Sjogren's syndrome.cite journal
author=Mandl T, Bredberg A, Jacobsson LT, Manthorpe R, Henriksson G
title=CD4+ T-lymphocytopenia--a frequent finding in anti-SSA antibody seropositive patients with primary Sjögren's syndrome
journal=J. Rheumatol.
volume=31
issue=4
pages=726–8
year=2004
month=April
pmid=15088298
doi=
url=http://www.jrheum.com/subscribers/04/04/726.html]

Because all of the reported autoimmune diseases and lymphomas involve B cells, one hypothesis proposes that ICL's narrow T cell repertoire predisposes the immune system to B cell disorders.

Epidemiology

ICL is a very rare disease. In 1993, a total of 47 confirmed cases were reported in a survey sponsored by the Centers for Disease Control. [cite journal | author = Smith D, Neal J, Holmberg S | title = Unexplained opportunistic infections and CD4+ T-lymphocytopenia without HIV infection. An investigation of cases in the United States. The Centers for Disease Control Idiopathic CD4+ T-lymphocytopenia Task Force. | journal = N Engl J Med | volume = 328 | issue = 6 | pages = 373–9 | year = 1993 | pmid = 8093633]

References