Efficacy and prognostic value of peripheral blood CD4+ T cells and serum IL-6 and IL-8 in tuberculous meningitis.

Objective: To investigate the value of peripheral blood clusters of differentiation 4 (CD4+) T-lymphocyte (T cells) count and serum interleukin-6 (IL-6) and interleukin-8 (IL-8) in the treatment and prognosis of tuberculous meningitis (TBM). Methods: Sixty-five patients with TBM were prospectively included in the observation group. Sixty-five patients with pulmonary TB and a group of 65 healthy individuals served as the control groups. The differences in peripheral blood CD4+ T-cell count, serum IL-6, and IL-8 levels were compared, and changes in these indices after anti-TB treatment in the observation group were analysed. The observation group was divided into effective and ineffective groups based on their response after 24 weeks of anti-TB treatment. The study also evaluated the influence of peripheral blood CD4+ T-cell count, serum IL-6, and IL-8 levels on the adverse prognosis of TBM during anti-TB treatment. Results: Before treatment, the CD4+ T-cell count in the peripheral blood of the observation group was lower than in both the control and healthy groups, and serum IL-6 and IL-8 levels were higher than in the control group (P < 0.001). After 24 weeks of anti-TB treatment, the CD4+ T-cell count in the peripheral blood of the observation group increased, whereas the levels of IL-6 and IL-8 decreased significantly (P < 0.001). The levels of CD4+ T cells and IL-6 in the peripheral blood of patients before treatment were identified as independent factors influencing the efficacy of anti-TB treatment (odds ratio [OR] = 0.989, 95 % confidence interval [CI]: 0.980-0.997; OR = 1.010, 95 % CI: 1.003-1.017). Conclusion: In patients with TBM, the CD4+ T-cell count in the peripheral blood is decreased, whereas serum IL-6 and IL-8 are increased. The combination of CD4+ T cells and IL-8 shows a degree of predictive value for the prognosis of anti-TB treatment.

Disseminated cryptococcosis in a patient with idiopathic CD4 + T lymphocytopenia presenting as prostate and adrenal nodules: diagnosis from pathology and mNGS, a case report.

Disseminated Cryptococcosis infection typically occurs in immunocompromised patients, often manifested as pneumonia or meningoencephalitis. Cases with involvement of either prostate or adrenal glands are less frequent. We describe a case of an immunocompromised 62-year-old man with new-found Idiopathic CD4 + T lymphocytopenia who presented with urinary irritation symptoms followed by headache. The patient was finally diagnosed as disseminated cryptococcosis of prostate, adrenal gland involvement with the help of combining histopathology of formalin-fixed, paraffin-embedded tissue with metagenomic next-generation sequencing technique to identify C neoformans sensu stricto in prostate, adrenal gland tissues. Clinicians should be aware of atypical presentations of cryptococcal disease. In this case of cryptococcosis in immunocompromised patients, we find that cryptococcosis can affect varied organs simultaneously and should be considered in the differential of infectious diseases. And mNGS technology helps to confirm the diagnosis.

Neonatal immunization prevents the development of a chronic autoimmune response against CD4 caused by HIV-1 gp120 in rats.

The AIDS autoimmune hypothesis suggests that suppression of the autoimmunity against CD4 T lymphocytes should positively affect the course of HIV infection. The aim of this study was to determine whether neonatal immunization can be used to prevent induction of anti-CD4 autoimmune response triggered by HIV-1. The induction of anti-CD4 lymphocytes in HIV infection proceeds via their idiotypic interactions with anti-gp120 lymphocytes; therefore, the creation of tolerance to gp120 by means of neonatal immunization with gp120 may prevent subsequent induction of anti-CD4 lymphocytes. Neonatal immunization with CD4 may also be effective, since it can increase natural tolerance to CD4 and prevent its subsequent breakdown by gp120. Thus, anti-gp120 lymphocytes and anti-CD4 lymphocytes are potential neonatal stimulation targets. To determine which of these targets can be manipulated during the neonatal period, a computer model of the immune network was used. The computer model predictions were tested in a rat model of autoimmune CD4 T lymphocytopenia induced by gp120. The in silico studies predicted that stimulating a clone against an external antigen that is in idiotype-anti-idiotype interactions with an autoclone, when stimulation is performed during the time that the dynamic behavior type of the immune network is being established, changes the autoimmune response from self-perpetuating to transient. Experimental studies confirmed the predictions of the computer model and showed that neonatal immunization with gp120 suppresses anti-CD4 autoantibody production and prevents the development of autoimmune CD4 T lymphocytopenia triggered in adult rats by gp120. Neonatal HIV-1 gp120 immunization enhances natural tolerance to CD4.

Disseminated cryptococcosis with varicella-zoster virus coinfection of idiopathic CD4 + T lymphocytopenia: a case report and literature review.

BACKGROUND: Idiopathic CD4 + T lymphocytopenia (ICL) is a rare immunodeficiency syndrome, unaccompanied by various opportunistic infections. Cryptococcus and varicella-zoster viruse are the most common opportunistic infections. METHOD: We described a case of disseminated cryptococcosis with varicella-zoster virus coinfection in a patient with ICL and reviewed all published reports. A total of 26 cases with cryptococcal meningitis in ICL were enrolled. DISCUSSION: ICL remains poorly understood to clinicians. Patients with cryptococcal meningitis in ICL mostly suffered with headache and fever in a subacute or chronic period, while some patients might have atypical manifestations which makes a difficulty for early diagnosis. Some characteristics of cerebrospinal fluid can help to predict the prognosis of the disease. Cryptococcosis with varicella-zoster virus coinfection is rare but serious. CONCLUSION: We recommed CD4 + T cells should be assessed in patients with unusual or recurrent infections. As the underlying pathophysiology is poorly understood, there is no standard therapy for ICL. Increased awareness of the disease and early prevention for CD4 reduction are needed.

EBER+ extranodal NK/T lymphoma in patient with idiopathic CD4 lymphocytopenia.

Idiopathic CD4 lymphocytopenia (ICL) not related to HIV is an infrequent and severe condition with no etiology defined until now. The concomitant presence of an underlying disease, especially an oncohematological process, could be related to the immune physiopathology and the development of the immunosuppressive state. On the other hand, Epstein Barr virus is a well-known oncogenic pathogen described in the development of several types of lymphoma which might be reactivated in the ICL. There is still no specific treatment for this syndrome, so the therapeutic scope for these patients is the treatment of opportunistic diseases and the administration of specific antimicrobials as prophylaxis. We present a patient with an uncommon association of an ICL and an extranodal T/NK lymphoma with detection of VEB nuclear RNA by in situ hybridization (EBER). Diagnosis was challenging which led the health team to carry out many studies over several months.

La linfocitopenia CD4 idiopática (ICL) no relacionada al HIV es una condición grave e infrecuente sin una etiología aún definida. La presencia de una enfermedad subyacente, especialmente un proceso oncohematológico, podría tener relación en la fisiopatología del proceso inmunológico. Por otro lado, el virus Epstein Barr (VEB) es bien conocido por ser un patógeno oncogénico descrito en el desarrollo de diversos tipos de linfomas, el cual podría ser reactivado en estados de inmunosupresión severa. No existe aún un tratamiento específico para este síndrome, por lo que el objetivo terapéutico en estos pacientes radica en el manejo profiláctico y activo de las distintas enfermedades oportunistas ante las cuales son susceptibles. Se presenta un paciente con un déficit grave de linfocitos CD4 de causa idiopática, y un diagnóstico posterior de linfoma T/NK extraganglionar con detección de RNA nuclear de VEB por hibridización in situ (EBER), una asociación poco descrita en la literatura médica.

EBER + extranodal NK/T lymphoma in patient with idiopathic CD4 lymphocytopenia / Linfoma T/NK EBER positivo en paciente con linfocitopenia CD4 idiopática

Abstract Idiopathic CD4 lymphocytopenia (ICL) not related to HIV is an infrequent and severe condition with no etiology defined until now. The concomitant presence of an underlying disease, especially an oncohematological process, could be related to the immune physiopathology and the development of the im munosuppressive state. On the other hand, Epstein Barr virus is a well-known oncogenic pathogen described in the development of several types of lymphoma which might be reactivated in the ICL. There is still no specific treatment for this syndrome, so the therapeutic scope for these patients is the treatment of opportunistic diseases and the administration of specific antimicrobials as prophylaxis. We present a patient with an uncommon asso ciation of an ICL and an extranodal T/NK lymphoma with detection of VEB nuclear RNA by in situ hybridization (EBER). Diagnosis was challenging which led the health team to carry out many studies over several months

Resumen La linfocitopenia CD4 idiopática (ICL) no relacionada al HIV es una condición grave e infrecuente sin una etiología aún definida. La presencia de una enfermedad subyacente, especialmente un proceso oncohematológico, podría tener relación en la fisiopatología del proceso inmunológico. Por otro lado, el virus Epstein Barr (VEB) es bien conocido por ser un patógeno oncogénico descrito en el desarrollo de diversos tipos de linfomas, el cual podría ser reactivado en estados de inmunosupresión severa. No existe aún un tratamiento específico para este síndro me, por lo que el objetivo terapéutico en estos pacientes radica en el manejo profiláctico y activo de las distintas enfermedades oportunistas ante las cuales son susceptibles. Se presenta un paciente con un déficit grave de linfocitos CD4 de causa idiopática, y un diagnóstico posterior de linfoma T/NK extraganglionar con detección de RNA nuclear de VEB por hibridización in situ (EBER), una asociación poco descrita en la literatura médica.

Criptococosis meníngea en un paciente con linfopenia T-CD4+ idiopática / Cryptococcal meningitis in a patient with idiopathic CD4+ T lymphopenia

RESUMEN La infección por el virus de la inmunodeficiencia humana es el factor de riesgo principal para desarrollar criptococosis meníngea; sin embargo, existe una entidad poco conocida, la linfopenia T-CD4+ idiopática, que genera un inexplicable déficit de células T-CD4+ circulantes predisponiendo a variadas complicaciones, entre ellas la infección por gérmenes oportunistas. Presentamos el caso de un paciente con criptococosis meníngea secundaria a una linfopenia T-CD4+ idiopática, que a nuestro conocimiento es el primer caso reportado en el Perú. Esta enfermedad debería considerarse en pacientes negativos para el virus de inmunodeficiencia humana, que cursen con infecciones infrecuentes del sistema nervioso central, ya que la evolución, manejo y pronóstico podrían ser distintos en pacientes con esta condición.

ABSTRACT Infection with the human immunodeficiency virus (HIV) is the main risk factor for developing cryptococcal meningitis. However, there is a poorly known entity, idiopathic CD4+ T-cell lymphopenia, which leads to an unexplainable CD4+ circulating T-cell deficit, predisposing patients to many complications, including infections caused by opportunistic microorganisms. We present the case of a patient with cryptococcal meningitis secondary to idiopathic T-CD4+ lymphopenia, which, as far as we know, is the very first case of its kind reported in Peru. This entity should be considered in patients negative for HIV infection developing non-common infections of the central nervous system, since outcome, management, and prognosis may be different in patients with this condition.

Criptococosis y linfocitopenia T CD4 idiopática: Reporte de un caso / Cryptococcosis and idiopathic CD4 T lymphocytopenia: A case report

Resumen La linfocitopenia T CD4 idiopática (LCI) es un síndrome clínico inusual que se caracteriza por un déficit de células T CD4+ circulantes en ausencia de infección por VIH u otra condición de inmunosupresión. Los pacientes con dicha enfermedad pueden presentarse asintomáticos o con infecciones oportunistas, las más frecuentes son por criptococo, micobacterias o virales como herpes zoster. Presentamos el caso de un hombre de 32 años, sin antecedentes, en quien se descartó infección por retrovirus, con recuento de linfocitos T CD4+ menor a 300 células/m3; se diagnosticó LCI posterior al diagnóstico de criptococomas cerebrales mediante hallazgos imagenológicos los cuales fueron congruentes con estudios microbiológicos.

Summary Idiopathic CD4 T lymphocytopenia (ICL) is an unusual clinical syndrome characterized by a deficit of circulating CD4 + T cells in the absence of HIV infection or another immunosuppression condition. Patients with this disease may present asymptomatic or with opportunistic infections, the most frequent are cryptococcus, mycobacteria or viral such as herpes zoster. We present a case of a 32-year-old man with no prior disease, in whom retrovirus infection was discarded, with CD4 + T lymphocyte count less than 300 cells/m3; ICL was diagnosed after the diagnosis of brain cryptococomas by imaging findings which were consistent with microbiological studies.

Infección por citomegalovirus en púrpura de Henoch-Schönlein del anciano como complicación y factor perpetuador de la enfermedad. Reporte de caso / Cytomegalovirus infection and Henoch-Schönlein purpura in the elderly as a complication and factor that perpetuates the disease. Case report

RESUMEN La púrpura de Henoch-Schönlein en el adulto es un reto diagnóstico. Su baja incidencia y su sintomatología poco específica configuran un cuadro clínico que puede pasar desapercibido en diversas ocasiones o solaparse bajo el peso de diferentes sospechas diagnósticas. La púrpura de Henoch-Schönlein no es un cuadro de espectro único. Se considera un grupo de enfermedades de manifestación heterogénea con un eje patogénico común dado por el hallazgo de inflamación de la pared en vasos de pequeño calibre mediada por complejos inmunes. Este es el caso de un paciente de 70 arios quien cursa con un cuadro compatible con púrpura de Henoch-Schönlein, de inicio tardío, caracterizada por su difícil manejo y constantes recaídas. a pesar del uso cuidadoso de las pautas terapéuticas establecidas por los consensos actuales. En este paciente se documentó, de forma concomitante, una infección por citomegalovirus que al recibir tratamiento permitió el control adecuado de síntomas. Adicionalmente, este paciente presentaba una linfocitopenia que parecía ser secundaria a la infección viral.

ABSTRACT Henoch-Schönlein purpura in the adult is a diagnostic challenge. Its low incidence and its unspecific symptomatology in this age group, establish a clinical chart that can be ignored on several occasions. Henoch-Schönlein purpura is considered a group of diseases of heterogeneous manifestation with a common pathogenic axis: the finding of inflammation of the wall of the small calibre vessels, mediated by immune complexes. The case is presented of a 70-year-old patient with a difficult to treat Henoch-Schönlein purpura, with constant relapses despite the use of the therapeutic guidelines established in the current guidelines. In this patient, a concomitant cytomegalovirus infection was documented that, after receiving treatment, allowed adequate control of symptoms. Additionally, this patient also had a lymphocytopenia that was secondary to cytomegalovirus.

Hypomyopathic Dermatomyositis Presenting with Idiopathic CD4 T-lymphocytopenia and Delayed Anti-MDA5 Positivity.

A 47-year-old Haitian male with no known past medical history was admitted to the hospital for gradually progressive dyspnea, nonproductive cough, and weight loss. He also endorsed a one-year history of joint pains. He was febrile and tachycardic and in mild respiratory distress. Other pertinent physical examination findings included diffuse inspiratory crackles, digital ulcers, and symmetric swelling of the wrists, elbows, shoulders, and knees. He was found to have a right basilar consolidation on chest computed tomography (CT) and was placed on antibiotics for presumptive pneumonia. His CD4 count was 158 cells per microliter despite testing negative for human immunodeficiency virus (HIV). A thorough infectious workup was unrevealing, and he did not improve with antibiotics. He had a weakly positive anti-nuclear antibody (ANA) with an otherwise negative rheumatologic workup. Creatinine kinase and aspartate aminotransferase were mildly elevated in the absence of overt muscle weakness. A myositis panel, including melanoma differentiation-associated protein five (anti-MDA5) antibody, was negative at the time. He was discharged on a short course of prednisone without a definitive diagnosis. He returned several months later with worsening respiratory symptoms. At this time, a lung biopsy revealed interstitial lung disease. Repeat myositis panel demonstrated anti-MDA5 positivity. The patient was also found to have new-onset non-ischemic heart failure with reduced ejection fraction. A diagnosis of hypomyopathic dermatomyositis was made based on clinical, laboratory, and imaging findings. The patient was restarted on prednisone, and mycophenolate mofetil was subsequently initiated for maintenance therapy.

Pulmonary nocardiosis in a patient with idiopathic CD4 T-lymphocytopenia.

Idiopathic CD4 T-lymphocytopenia (ICL) is a rare immunodeficiency characterized by low CD4 T-lymphocyte count, which usually manifests with opportunistic infections. Nocardia as an opportunistic pathogen infecting patients with this condition has rarely been reported. Here, we describe the case of a 46-year-old male who presented with lung mass and respiratory and systemic symptoms and was eventually diagnosed with pulmonary nocardiosis. A workup for predisposing immunodeficiencies suggested a picture of ICL. This case illustrates the importance of considering ICL as a possible predisposing condition when an otherwise healthy individual presents with pulmonary nocardiosis.

Nocardia otitidiscaviarum meningitis in a diffuse large B-cell lymphoma patient with CD4-positive lymphocytopenia and persistent oligoclonal CD8-positive lymphocytes in the peripheral blood.

Nocardiosis, sometimes presenting with multiple granulomatous lesions, is a rare opportunistic infection occurring in immunocompromised patients. However, its immunological features remain largely unaddressed. We investigated the immunological characteristics of human nocardiosis and examined the component cells of the granulomatous lesions. A 66-year-old man with diffuse large B-cell lymphoma presented with fever and multiple nodules in the lung during chemotherapy. The blood culture formed white colonies, but their characterization was difficult by routine microbiological laboratory methods. Matrix-assisted laser desorption ionization-time of flight mass spectrometry identified the colonies as Nocardia otitidiscaviarum. Meanwhile, the patient suddenly experienced an epileptic seizure without a brain abscess. His cerebrospinal fluid (CSF) showed neutrophilic pleocytosis (108/mm3). The conventional agar culturing failed to isolate colonies, but culturing with brain-heart infusion agar generated colonies. These colonies were completely concordant with those from the blood, as confirmed by 16S rRNA gene sequencing. Therefore, the patient had developed meningitis through sepsis induced by N. otitidiscaviarum. His CD4-positive T-lymphocyte counts were low, and oligoclonal CD8-positive αß T-lymphocytes were present in the blood prior to the first and after three cycles of chemotherapy. He had bone marrow granulomatous lesions comprising lymphoma and CD8-positive αß T-cells. Treatment with sulfamethoxazole/trimethoprim relieved all of his symptoms. The combined analysis by microbiological and molecular methods determined the cause of his epileptic seizure. His immunological characteristics, including low CD4-positive or CD8-positive αß T-lymphocytes, may have contributed to the unusual clinical presentations by N. otitidiscaviarum, which rarely involves the central nervous system.

Pneumocystis Pneumonia Secondary to Idiopathic CD4+ T-lymphocytopenia: A Comparison of AIDS and Non-AIDS Patients.

A 67-year-old man was admitted to our hospital complaining of dry cough. Chest computed tomography showed diffuse infiltrates and ground-glass opacities in the bilateral lung fields. Transbronchial lung biopsy specimens showed alveoli filled with yeast-like fungi. With a diagnosis of pneumocystis pneumonia (PCP), he was given oral sulfamethoxazole/trimethoprim, to which he responded well. However, seven months later, PCP relapsed. Analyses revealed a low bronchoalveolar lavage fluid CD4/CD8 ratio of 0.04 and CD4+ lymphocytopenia (250/µL). Despite intensive work-up, we were unable to detect the underlying cause of CD4+ lymphocytopenia; therefore, a final diagnosis of idiopathic CD4+ T-lymphocytopenia was made.

CD4+ T lymphocytopenia associated with sideropenia: case report

Importance of the issue: Idiopathic CD4 T lymphocytopenia is an unusual immune defect in which there is an unexplained deficit of CD4 T cells. This case presents a 39-year-old female patient, with CD4+ T lymphocytopenia, who was not infected with immunosuppressive viruses neither was she subjected to immunosuppressive therapies. Comments: While monitoring the patient, she was found to have very low serum ferritin and, after parenteral iron therapy, there were changes in CD4+ cell levels, indicating that, in this case, lymphocytopenia was secondary to sideropenia. The patient is being kept under strict control of serum iron and periodic immunological evaluation, and she has not showed any clinical and/or laboratory adverse events so far. It is known that iron deficiency is an important factor in the genesis of immunological changes that occur in patients with iron deficiency anemia. It is important to understand the effects of iron deficiency on the immune system due to its high prevalence worldwide. Moreover, it could also help to clarify several cases of idiopathic CD4 lymphocytopenia (AU)

Importância da questão: Linfocitopenia T CD4+ idiopática é um defeito imune incomum em que há um déficit inexplicável de células T CD4. Este caso clínico apresenta uma paciente do sexo feminino de 39 anos de idade, com linfocitopenia T CD4+, que não estava infectada por vírus imunossupressores nem foi submetida a terapias imunossupressoras. Comentários: Durante o acompanhamento da paciente, ela apresentou níveis muito baixos de ferritina sérica e, após a terapia parenteral de ferro, houve aumento da quantidade de células CD4+, indicando que, neste caso, linfocitopenia era secundária à sideropenia. A paciente estava sendo mantida sob rigoroso controle de ferro sérico e avaliação imunológica periódica, e não mostrou quaisquer eventos adversos clínicos e/ou laboratoriais até o momento. Com base em mudanças na reatividade imunológica dos pacientes observadas por outros pesquisadores após a suplementação com ferro, é evidente que a deficiência de ferro seria um fator importante na gênese das alterações imunológicas que ocorrem em pacientes com anemia ferropriva. É importante compreender os efeitos da deficiência de ferro no sistema imune, devido à sua elevada prevalência mundial. Essas informações também auxiliariam a esclarecer vários casos de linfocitopenia T CD4+ idiopática. (AU)

Interleucina-2 no tratamento adjuvante de paciente com linfocitopenia CD4 idiopática e tuberculose disseminada / Interleukin 2 as adjuvant treatment in a patient with idiopathic CD4 lymphocytopenia and disseminated tuberculosis

Linfocitopenia CD4 idiopática (LCI) é uma imunodeficiência rara e grave caracterizada por uma diminuição inexplicável da contagem absoluta de linfócitos T CD4, a qual está associada a infecções oportunistas. Existem poucos relatos de casos na literatura que descrevem a IL2 como uma opção terapêutica em infecções oportunistas associadas à LCI. Relatamos os benefícios da adição de IL2 ao tratamento padrão em um paciente com ICL e infecções oportunistas. Um homem de 38 anos de idade foi internado por acidente vascular cerebral isquêmico devido à vasculite infecciosa. A análise do líquido cefalorraquidiano mostrou meningite neutrofílica. Cultura e PCR foram positivos para Mycobacterium tuberculosis. A tomografia de tórax foi compatível com tuberculose pulmonar. O paciente também apresentava candidíase oral, onicomicose e dermatite seborreica. A contagem de células sanguíneas mostrou linfocitopenia. O tratamento padronizado para tuberculose disseminada (RIPE) e fluconazol foram iniciados e mantidos em casa após a alta do paciente. Após cinco meses de seguimento, o paciente foi encaminhado ao imunologista clínico, pois não apresentava melhora clínica significativa, tendo sido hospitalizado diversas vezes. A avaliação imunológica mostrou uma contagem sanguínea de CD4 T consistentemente inferior a 100 células/mm3 e o diagnóstico de LCI foi confirmado (linfocitopenia inexplicável com menos de 300 células/mm3 ou menos de 20% de células T CD4+ em mais de uma ocasião com pelo menos 2 meses de intervalo). O paciente também apresentava episódios raros de linfocitopenia de células B e hipogamaglobulinemia, tendo recebido gamaglobulina. Como tratamento adjuvante, a IL2 subcutânea foi associada ao tratamento padronizado. Até agora, o paciente recebeu cinco ciclos consecutivos de IL2, mostrando melhora clínica e aumento da contagem de células T CD4 no sangue, atingindo um valor máximo de 401 células/mm3. As células CD8, B e natural killer também aumentaram. Novas análises do líquido cefalorraquidiano foram normais, e a cultura de Mycobacterium tuberculosis e a PCR foram negativas. Nosso paciente com infecções oportunistas associadas à LCI apresentou evolução laboratorial e clínica favoráveis após a adição de IL2 ao tratamento padrão. Este relato de caso apoia o uso de IL2 como um coadjuvante seguro e potencialmente eficaz para infecções oportunistas associadas à LCI. O caso destaca a importância da avaliação e acompanhamento de pacientes com suspeita de imunodeficiência por imunoalergologistas.

Idiopathic CD4 T lymphocytopenia (ICL) is a rare and severe immunodeficiency disorder characterized by an unexplained decrease of absolute CD4 T-lymphocyte cell counts, which is associated with opportunistic infections. There are few case reports in the literature describing the use of interleukin 2 (IL2) as a therapeutic option in ICL-associated opportunistic infections. We report the benefits of adding IL2 to the standard treatment in a patient with ICL and opportunistic infections. A 38-year-old male patient was admitted with ischemic stroke due to infectious vasculitis. Cerebrospinal fluid analysis revealed neutrophilic meningitis. Culture and PCR were positive for Mycobacterium tuberculosis. Chest CT was compatible with pulmonary tuberculosis. The patient also presented oral candidiasis, onychomycosis, and seborrheic dermatitis. Blood cell count revealed lymphocytopenia. Standardized treatment for disseminated tuberculosis (RIPE therapy) and fluconazole were initiated and maintained at home after the patient's discharge. After five months of follow-up, the patient was referred to a clinical immunologist, due to the absence of significant clinical improvement, with multiple hospitalizations over the follow-up period. Immunological assessment showed CD4 T cell counts consistently below 100 cells/mm3, and the diagnosis of ICL was confirmed (unexplained lymphocytopenia with less than 300 cells/mm3 or less than 20% of CD4+ T cells on more than one occasion at least 2 months apart). The patient also presented rare episodes of B cell lymphocytopenia and hypogammaglobulinemia, treated with gammaglobulin. As an adjuvant treatment, subcutaneous IL2 was added to the standard treatment. So far the patient underwent five consecutive cycles of IL2, showing clinical improvement and increased CD4 T cell counts, reaching a maximum value of 401 cells/mm3. CD8, B and natural killer cells also increased. New cerebrospinal fluid analyses were normal, and new Mycobacterium tuberculosis culture and PCR were negative. Our patient had opportunistic infections associated with ICL and presented favorable laboratory and clinical outcomes after the association of IL2 to the standard treatment. This case report supports the use of IL2 as a safe and potentially effective adjuvant treatment for ICL-associated opportunistic infections. The case highlights the importance of immunological assessment and follow-up of patients with suspected immunodeficiency.

Isolated Cerebellar Spindle Cell Pseudotumor Caused by Mycobacterium Avium-Intracellulare Complex in a Patient without AIDS.

BACKGROUND: Spindle cell pseudotumors are formed by histiocytes in response to infection by Mycobacterium avium-intracellulare complex (MAC) and are rare in patients without AIDS. CASE DESCRIPTION: A 66-year-old man presented with neck pain, ataxia, and a history of sarcoidosis. A cerebellar lesion was identified on magnetic resonance imaging and surgically excised. Histopathology revealed this to be a spindle cell pseudotumor and MAC was isolated by bacterial culture of cerebrospinal fluid. Hematology revealed cluster of differentiation 4 lymphocytopenia but human immunodeficiency virus serology was negative. The patient was commenced on antimicrobial treatment that included a macrolide and remained well at 1 year follow-up. CONCLUSIONS: This rare presentation of isolated intracranial MAC was treated with surgical excision and antimicrobials with a good outcome.

An unusual complication after interventional cardiology reveals and infrequent condition: Idiopathic CD4 deficiency.

Herpes zoster (HZ) is of rare occurrence after interventional procedures with few events reported until now. A 74 year-old man with a past medical history of idiopathic thrombocytopenic purpura, splenectomy, autoimmune hemolytic anemia, and polymyalgia rheumatica developed HZ on the right median nerve 7 days after he underwent a coronariography for managing an acute coronary syndrome. He evolved with cutaneous dissemination and required intravenous acyclovir therapy. Laboratory evaluation disclosed a previously unknown idiophatic CD4 lymphocytopenia. HZ should be added to the list of complications after interventional cardiology and associated immunosuppressive factors ruled out.

Progressive multifocal leukoencephalopathy in common variable immunodeficiency: mitigated course under mirtazapine and mefloquine.

Demonstration of survival and outcome of progressive multifocal leukoencephalopathy (PML) in a 56-year-old patient with common variable immunodeficiency, consisting of severe hypogammaglobulinemia and CD4+ T lymphocytopenia, during continuous treatment with mirtazapine (30 mg/day) and mefloquine (250 mg/week) over 23 months. Regular clinical examinations including Rankin scale and Barthel index, nine-hole peg and box and block tests, Berg balance, 10-m walking tests, and Montreal Cognitive Assessment (MoCA) were done. Laboratory diagnostics included complete blood count and JC virus (JCV) concentration in cerebrospinal fluid (CSF). The noncoding control region (NCCR) of JCV, important for neurotropism and neurovirulence, was sequenced. Repetitive MRI investigated the course of brain lesions. JCV was detected in increasing concentrations (peak 2568 copies/ml CSF), and its NCCR was genetically rearranged. Under treatment, the rearrangement changed toward the archetype sequence, and later JCV DNA became undetectable. Total brain lesion volume decreased (8.54 to 3.97 cm(3)) and atrophy increased. Barthel (60 to 100 to 80 points) and Rankin (4 to 2 to 3) scores, gait stability, and box and block (7, 35, 25 pieces) and nine-hole peg (300, 50, 300 s) test performances first improved but subsequently worsened. Cognition and walking speed remained stable. Despite initial rapid deterioration, the patient survived under continuous treatment with mirtazapine and mefloquine even though he belongs to a PML subgroup that is usually fatal within a few months. This course was paralleled by JCV clones with presumably lower replication capability before JCV became undetectable. Neurological deficits were due to PML lesions and progressive brain atrophy.

Cutaneous Penicillium marneffei infection in a patient with idiopathic CD4(+) lymphocytopenia.

We describe a case of cutaneous Penicillium marneffei infection in a non-HIV-infected male patient with idiopathic CD4(+) T lymphocytopenia (ICL). The cutaneous lesions were cured after the treatment of itraconazole combined with interleukin-2.