Isolated renal mucormycosis in a patient with Idiopathic CD4 lymphocytopenia.

Idiopathic CD4 lymphocytopenia (ICL) is characterised by a low CD4 +lymphocyte count in the absence of HIV or other underlying aetiologies. We report a case of a 17-year-old girl with ICL with autoimmune hepatitis who developed isolated renal mucormycosis, which, to our knowledge, is the first reported case described in literature. Combination therapy with antifungals and surgical resection was done, and the patient improved. This case report illustrates the importance of timely multidisciplinary approach to recognise this highly fatal disease at an early stage.

Radiology Case of the Month: Idiopathic CD4 Lymphocytopenia.

A 39 year-old male with a history of diabetes, retinitis pigmentosa, and genital warts presented with intractable occipital headaches accompanied with nausea and vomiting. The patient had markedly depressed CD4 counts. Furthermore the patient tested negative for HIV and HTLV 1/2 and had normal immunoglobulin levels. During hospital course the patient underwent a lumbar puncture and multiple imaging exams, including both CT and MR. Except for occasional nausea and vomiting controlled by therapeutic lumbar punctures, phenergan, and dilaudid the patient's hospital course was uncomplicated.

Idiopathic lymphocytopenia.

PURPOSE OF REVIEW: Idiopathic CD4⁺ lymphocytopenia (ICL) is defined by the reduction of the main lymphocyte subtype in peripheral blood and CD4⁺ T cells below 300/µl in the absence of any secondary known causes of lymphopenia, including viral causes. The present review aims to state the latest available data on clinical, pathological and therapeutic aspects related to ICL, published from 1990 to 2014. The last observed clinical presentation and complications of ICL patients are described. The latest findings and possible mechanisms involved in the development of ICL features are included in the present review; however, pathogenesis of ICL has remained mainly obscured. Finally, recent therapeutic efforts considered in ICL patients are discussed. RECENT FINDINGS: In spite of the serious complications ICL has on the patients' quality of life, data on clinical, etiopathological and therapeutic behavior for ICL are very limited. On one side, an abnormal blood cell count may be the sole presentation; however, occurrence of disseminated malignant tumors is not uncommon in patients. Recent findings highlight the role of cytokines, especially interleukin-2, on features such as phenotype severity and responsiveness of the condition to therapy. In addition, some studies have suggested that a defect in hematopoietic stem cells may be involved in disease progression, an idea that is supported by the success of bone marrow transplantation in acquiring persistent remissions in ICL patients. SUMMARY: ICL is a hematologic condition of increasing importance due to its diverse clinical and pathological spectrum. Molecular studies have shown the presence of mutations involved in lymphocyte development as potential factors that may contribute to ICL occurrence. ICL patients could present either with common infections or really serious malignant conditions. The role of cytokines, especially interleukin-2, has emerged as one of the main possible mechanisms involved in clinical and pathological behavior of ICL. Today, the main therapeutic approaches are controlling life-threatening infections and underlying disorders along with efforts to cure ICL through rising CD4⁺ cell counts using cytokine interventions and transplantation.

Idiopathic CD4 lymphocytopenia: a case of missing, wandering or ineffective T cells.

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.

Generalized verrucosis: a review of the associated diseases, evaluation, and treatments.

Generalized verrucosis has been described in the past as synonymous with epidermodysplasia verruciformis. It has been shown, however, that epidermodysplasia verruciformis and other genetic or immunodeficiency diseases are just a subset of diffuse infections with human papillomavirus termed "generalized verrucosis." This article defines generalized verrucosis and distinct diseases associated with generalized warts. The indications for histopathologic testing, human papillomavirus typing, and other laboratory analyses and potential treatment options are discussed.

Non-myeloablative hematopoietic stem cell transplantation in the treatment of severe idiopathic CD4+ lymphocytopenia.

A 40-year-old man with severe chronic idiopathic CD4+ lymphocytopenia complicated with opportunistic infections was successfully treated with non-myeloablative allogeneic hematopoietic stem cell transplantation. After conditioning with fludarabine plus low dose of total-body irradiation, CD34+ peripheral blood stem cells obtained by leukapheresis from his HLA-identical sister were infused. T cell and myeloid complete chimerism was achieved at day +28 and remained stable during the follow-up period. The patient did not develop infectious complications during the procedure. At 35 months of follow-up, his CD4+ T cell count was 1019 cells per microliter. Non-myeloablative allogeneic hematopoietic stem cell transplantation should be considered a treatment option for patients with severe forms of idiopathic CD4+ lymphocytopenia.

Idiopathic CD4+ T-cell lymphocytopenia is associated with impaired membrane expression of the chemokine receptor CXCR4.

Idiopathic CD4(+) T-cell lymphocytopenia (ICL) is a rare acquired T-cell immunodeficiency of unknown pathogenic basis. Six adults with ICL who developed opportunistic infections were investigated using extensive immunophenotyping analysis and functional evaluation of the chemokine receptor CXCR4. For all 6 patients studied, a profound defect in CXCR4 expression was detected at the surface of CD4(+) T lymphocytes, in association with an abnormal intracellular accumulation of CXCR4 and of its natural ligand, the chemokine CXCL12. For all patients studied, CD4(+) T-cell chemotactic response toward CXCL12 was decreased, whereas sensitivity to CXCL8 was preserved. CXCR4 recovery after ligand-induced endocytosis was impaired in ICL CD4(+) T cells. Upon in vitro addition of interleukin-2 (IL-2), membrane expression of CXCR4 returned to normal levels in 5 of 6 patients, whereas intracellular accumulation of CXCR4 and CXCL12 disappeared. Upon therapeutic administration of IL-2, CD4(+) T-cell count and membrane CXCR4 expression and function improved over time in 3 of 4 patients treated. Therefore, our data indicate that ICL is associated with defective surface expression of CXCR4, which may be reversed by IL-2.

Idiopathic CD4 lymphocytopenia and opportunistic infection--an update.

A severe CD4 T-cell depletion predisposes humans to opportunistic infections. In recent years, reports of cases of opportunistic infections caused by CD4 T-cell depletion without HIV infection have been accumulating. Such cases, termed idiopathic CD4 T lymphocytopenia (ICL), are very rare. The epidemiologic data do not suggest that the condition is caused by a transmissible agent. Unlike HIV infection, the decrease in the CD4 cell counts of patients with ICL is often slow. The clinical spectrum of ICL ranges from an asymptomatic laboratory abnormality to life-threatening opportunistic infections. However, the pathogens, clinical significance and treatment of ICL patients still await systematic research. This review summarizes the current knowledge of the poorly understood syndrome of idiopathic CD4 lymphocytopenia, providing key insights into the pathogenesis and immunologic characteristics, and suggesting approaches to enhance CD4 T-cell counts.

Cryptosporidium infection in patients with primary immunodeficiencies.

BACKGROUND: Cryptosporidium species infection is usually self-limited in immunocompetent populations, but can be severe and life-threatening among immunocompromised individuals, particularly in patients with AIDS and in these patients with primary immunodeficiencies (PIDs). PATIENTS AND METHODS: A group of 5 patients with genetically confirmed hyper-IgM syndrome type 1 (XHIM) and one patient with primary CD4 lymphopenia were enrolled in the study. At least 2 stool samples and a bile sample in one patient were examined for Cryptosporidium oocysts by a modified Ziehl-Neelsen technique, by immunofluorescence assay using a commercial kit, as well as by molecular analysis followed by genotyping. Immunological status at the time of PID diagnosis and the complex picture of disease are presented. RESULTS: Chronic cryptosporidiosis was confirmed in 3 patients with XHIM and in one patient with primary CD4 lymphopenia. Molecular diagnosis showed the presence of C parvum, C hominis, and C meleagridis in analyzed specimens. CONCLUSIONS: Cryptosporidium infection with serious clinical symptoms observed in patients with hyper-IgM syndrome calls for regular, repeated screening in this group of patients.

Presentación de cinco casos de linfocitopenia CD4+ idiopática / Report of five cases of idiopathic CD4+ lymphocytopenia

Introducción: el objetivo de este trabajo es llamar la atención sobre una inmunodeficiencia recientemente descripta y ofrecer una propuesta de estudio y tratamiento. Material y métodos: período de estudio: enero de 1998 a agosto de 2000. Presentamos 5 pacientes de entre 23 y 86 años de edad (media 51,2 años), todos de sexo femenino, que fueron estudiadas por presentar infecciones a repetición (micóticas, virales y bacterianas). Se les realizó determinación de VIH por ELISA, pruebas cutáneas para antígenos habitualmente reconocidos por el organismo, medición de linfocitos CD4+ y CD8+ por partículas magnéticas. Proteinograma electroforético, dosaje de inmunoglobulinas plasmáticas por inmunodifusión radial. Se efectuó tratamiento con timomodulina 60 mg por día. Conclusiones: al momento del diagnóstico se observó: pruebas cutáneas hipoérgicas, VIH negativo y disminución de linfocitos CD4+. Posterior al tratamiento con timomodulina, se observó buena respuesta clínica, mejoría de las pruebas cutáneas y elevación de los linfocitos CD4+ en todas las pacientes (AU)

Pulmonary Mycobacterium avium disease in a young patient with idiopathic CD4+ T lymphocytopenia.

A case of pulmonary Mycobacterium avium (M. avium) disease associated with idiopathic CD4+ T lymphocytopenia is reported. A rapidly growing pulmonary nodule was detected on a chest roentgenogram in a young man. Bronchoscopic examination revealed M. avium infection. Hematological studies showed a low CD4+ cell count in the absence of any identifiable immunodeficiency, including human immunodeficiency virus (HIV) infection. With the combination of chemotherapy and surgery, he had a good clinical outcome. Idiopathic CD4+ T lymphocytopenia should be considered in patients with unexplained opportunistic infection.

Allogeneic bone marrow transplantation can restore CD4+ T-lymphocyte count and immune function in idiopathic CD4+ T-lymphocytopenia.

CD4+ T-lymphocytopenia in the absence of HIV infection is a heterogeneous disorder of unknown cause. Here we report a patient with idiopathic CD4+ T-lymphocytopenia, presenting with an opportunistic Rhodococcus equi infection. When aplastic anemia developed subsequently, allogeneic bone marrow transplantation was performed. Complete restoration of immune function was observed. We conclude that allogeneic bone marrow transplantation presents a potentially curative therapy for CD4+ T-lymphocytopenia.

Lymphocyte subset diversity in idiopathic CD4+ T lymphocytopenia.

The clinical and public health importance of CD4+ T lymphocytopenia without human immunodeficiency virus infection is still unclear. We describe herein two new human immunodeficiency virus-negative patients with low numbers of peripheral CD4+ T cells and opportunistic infections (cerebral toxoplasmosis and tuberculosis plus extrapulmonary histoplasmosis). The low numbers of CD4+ CD29+ memory cells, the high percentage of gamma delta T-cell receptor cells, and the recovery of CD4+ cells after treatment were remarkable.

Response to interferon-alpha in patients with hairy cell leukemia relapsing after treatment with 2-chlorodeoxyadenosine.

2-Chlorodeoxyadenosine (2-CdA) has recently established itself as an extremely effective therapy for patients with hairy cell leukemia. To date, the issue of how to treat patients relapsing after 2-CdA has not been adequately addressed. In our initial study, 41 of 46 patients achieved an objective response (complete or partial remission). The only persistent toxicity associated with this agent appears to be significant suppression of CD4+ lymphocyte counts, albeit without evidence of clinical sequelae at a median follow-up of 30 months (range, 7-43). Eight patients have developed recurrent disease 3-23 months (median, 16 months) after 2-CdA. Because of progressive cytopenias, three of these patients were treated with interferon-alpha (IFN-alpha) (3 x 10(6) units subcutaneously three times per week), commencing 2, 9 and 16 months after the documentation of relapse. All three patients have shown an objective response with reduction of marrow hairy cells and amelioration of neutropenia and thrombocytopenia (two patients, complete remission; one patient, partial remission). Responses were maintained while on IFN-alpha, but two patients relapsed shortly (3 and 4 months, respectively) after discontinuation of IFN. There was no significant toxicity. Prior to commencing IFN-alpha, 22-36 months after 2-CdA, these patients' absolute CD4+ counts were suppressed (mean 211/microliters, s.d. +/- 85/microliters), but have not significantly changed after 10, 11 and 18 months of IFN-alpha therapy (mean 225/microliters, s.d. +/- 93/microliters). These results suggest that in hairy cell leukemia patients relapsing after 2-CdA, IFN-alpha may be a reasonable therapeutic option, especially if persistent CD4+ lymphocytopenia is present.

The syndrome of idiopathic CD4+ lymphocytopenia.

The syndrome of idiopathic CD4+ lymphocytopenia has recently been recognized and referred to as the persistent depletion of peripheral blood CD4+ T lymphocytes below 300 cells per cubic millimeter or less than 20% of total lymphocytes in the absence of either HIV infection or other known causes of immunodeficiency. The available literature indicates that neither human retroviruses (HIV-1, HIV-2, HTLV-I, HTLV-II) nor other transmissible agents play any clear-cut role in the pathogenesis. Furthermore, the epidemiologic, immunologic and clinical features of this syndrome differ substantially from those of HIV infection. The heterogeneity of both immunologic abnormalities, in addition to CD4+ depletion, and clinical course in patients with this disorder points out no common cause although in at least a subset of patients the pathogenetic pathways could be shared with common variable immunodeficiency.