Idiopathic CD4 Lymphocytopenia Manifesting as Refractory Genital Dysplasia

Department of Obstetrics and Gynecology and the Division of Allergy and Immunology, Department of Internal Medicine, Naval Medical Center, Portsmouth, Virginia
Obstetrics and Gynecology (Impact Factor: 5.18). 08/2013; 122(2 Pt 2):455-8. DOI: 10.1097/AOG.0b013e3182835850
Source: PubMed


Idiopathic CD4 lymphocytopenia is an immunodeficiency disorder with low absolute CD4 T-lymphocyte count with no evidence of human immunodeficiency virus or other known cause.
A 22-year-old woman presented with a high-grade Pap test result. Work-up demonstrated cervical intraepithelial neoplasia 3 and vaginal intraepithelial neoplasia 3 with extensive condyloma. She presented 6 months after her initial treatment with recurrent disease and was referred to the immunology department, where she was found to have profound lymphopenia. After further evaluation, idiopathic CD4 lymphocytopenia was diagnosed.
Idiopathic CD4 lymphocytopenia is a rare acquired immunodeficiency. Although genital dysplasia is common in young women, this case demonstrates the importance of determining other etiologies of recurrent human papillomavirus infections and possible immunodeficiencies that may affect management and outcomes.

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    ABSTRACT: The clinical and public health importance of recent reports of patients with CD4+ T-lymphocytopenia without human immunodeficiency virus (HIV) infection is unclear. We conducted investigations to determine the demographic, clinical, and immunologic features of patients with idiopathic CD4+ T-lymphocytopenia; whether the syndrome is epidemic or transmissible; and the possible causes. We reviewed 230,179 cases in the Centers for Disease Control and Prevention (CDC) AIDS Reporting System and performed interviews, medical-record reviews, and laboratory analyses of blood specimens from adults and adolescents who met the CDC case definition of idiopathic CD4+ T-lymphocytopenia (< 300 CD4+ cells per cubic millimeter or a CD4+ cell count < 20 percent of total T cells on two occasions and no evidence of infection on HIV testing), their sexual contacts, household contacts, and persons who had donated blood to them. We interviewed 31 of the 47 patients identified with idiopathic CD4+ T-lymphocytopenia and 23 of their contacts. There were 29 male and 18 female patients, with a mean age of 43 years (range, 17 to 78); 39 were white, 4 were Asian, 2 were Hispanic, and 2 were black. Eighteen patients (38 percent) had one or more risk factors for HIV infection: seven had hemophilia, six had engaged in homosexual sex, six had received blood transfusions, and two had had heterosexual sex partners who were at risk for HIV infection. The other 29 patients (62 percent) had no identified risk factors for HIV infection. Nineteen persons (40 percent) had AIDS-defining illnesses (18 had opportunistic infections), 25 (53 percent) had conditions that were not AIDS-defining, and 3 (6 percent) were asymptomatic. We tested blood from 28 patients: 8 (29 percent) were found to have CD4+ T-lymphocyte counts of less than 300 cells per cubic millimeter, and 6 had CD8+ T-lymphocytopenia (< 250 cells per cubic millimeter). Ten sex partners, three household contacts, and four children of the patients, as well as six persons who had donated blood to the patients, were immunologically and clinically normal. This investigation of patients with idiopathic CD4+ T-lymphocytopenia and unexplained opportunistic infections indicates that the disorder is rare and represents various clinical and immunologic states. The investigation of contacts revealed no evidence of a new transmissible agent that causes lymphocytopenia.
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    ABSTRACT: HPV infection in the genital tract is common in young sexually active individuals, the majority of whom clear the infection without overt clinical disease. However most of those who develop benign lesions eventually mount an effective cell mediated immune (CMI) response and the lesions regress. Failure to develop effective CMI to clear or control infection results in persistent infection and, in the case of the oncogenic HPVs, an increased probability of progression to CIN3 and invasive carcinoma. The prolonged duration of infection associated with HPV seems to be associated with effective evasion of innate immunity thus delaying the activation of adaptive immunity. Natural infections in animals show that neutralising antibody to the virus coat protein L1 is protective suggesting that this would be an effective prophylactic vaccine strategy. The current prophylactic HPV VLP vaccines are delivered i.m. circumventing the intra-epithelial immune evasion strategies. These vaccines generate high levels of antibody and both serological and B cell memory as evidenced by persistence of antibody and robust recall responses. However there is no immune correlate - no antibody level that correlates with protection. Recent data on how HPV infects basal epithelial cells and how antibody can prevent this provides a mechanistic explanation for the effectiveness of HPV VLP vaccines.
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    ABSTRACT: Idiopathic CD4 lymphocytopenia (ICL) is a presumed heterogenous syndrome with key element low CD4 T-cell counts (below 300/mm3) without evidence of HIV infection or other known immunodeficiency. The etiology, pathogenesis, and management of ICL remain poorly understood and inadequately defined. The clinical presentation can range from serious opportunistic infections to incidentally diagnosed asymptomatic individuals. Cryptococcal and non-tuberculous mycobacterial infections and progressive multifocal leukoencephalopathy are the most significant presenting infections, although the spectrum of opportunistic diseases can be similar to that in patients with lymphopenia and HIV infection. Malignancy is common and related to opportunistic pathogens with an oncogenic potential. Autoimmune diseases are also seen in ICL with an increased incidence. The etiology of ICL is unknown. Mechanisms implicated in CD4 reduction may include decreased production, increased destruction, and tissue sequestration. New distinct genetic defects have been identified in certain patients with ICL, supporting the hypothesis of the lack of a common etiology in this syndrome. The management of ICL is focused on the treatment of opportunistic infections, appropriate prophylactic antibiotics, and close monitoring. In selected patients with life-threatening infections or profound immunodeficiency, strategies to increase T-cell counts or enhance immune function could be considered and have included interleukin-2, interferon-gamma, interleukin-7, and hematopoietic stem cell transplantation. The prognosis is influenced by the accompanying opportunistic infections and may be affected by publication bias of severe cases with unfavorable outcomes. As newer laboratory investigation techniques are being developed and targeted experimental treatments become available, our comprehension and prognosis of this rare syndrome could be significantly improved.
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