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.

Disseminated Cryptococcosis in Idiopathic CD4+ Lymphocytopenia.

INTRODUCTION: Idiopathic CD4+ Lymphocytopenia (ICL) is a rare entity grouped in non- HIV-related syndromes. ICL is characterized by a marked low CD4 T cell count of <300 cells/mm3 with ambiguous natural history and prognosis. In addition, cryptococcal and nontuberculous mycobacterial infections are reported as known opportunistic infections. Therefore, management turns around vigilant follow-up and treatment of the current clinical scenario of these patients. CASE PRESENTATION: Here, a 55-year-old lady was referred with a history of diffuse headache and intermittent fever for two months, projectile vomiting, and altered mental status for five days. Nonpruritic maculopapular rashes and diffuse desquamation of the skin were noted. She had no significant previous medical history. Based on clinical findings and investigations, she was diagnosed with ICL having disseminated cryptococcosis. Unfortunately, the patient did not undergo specific treatment as she was recognized late, and unfortunately, she died. CONCLUSION: It is of paramount importance to recognize the clinical entity as early as possible to start appropriate treatment, which may positively impact the outcome. Therefore, the clinician must be aware of disseminated cryptococcosis associated with non-HIV states.

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.

Pulmonary sarcoidosis: prognostic factors at diagnosis in patients from North of Portugal / Sarcoidosis pulmonar: factores pronósticos en el diagnóstico en enfermos del norte de Portugal

BACKGROUND: Sarcoidosis is a multisystemic granulomatous disease that affects the lungs in more than 90% of the patients. It is associated with a variable clinical course and considering all the different forms of disease presentation, there are an absence of reliable clinical prognostic markers that can predict the outcome at diagnosis. OBJECTIVE: The aim of our study was to investigate prognostic factors at diagnosis in a population of sarcoidosis patients from Northern Portugal. METHODS: A group of 110 patients with chronic evolution was compared with 129 patients with disease resolution regarding their clinical, radiologic and laboratorial features. RESULTS: We found a positive association between the chronic forms and lung function impairment, radiologic stage II, lower lymphocyte CD4/CD8 and extrapulmonary disease. Löfgren syndrome and asthenia instead had a protective significant association to chronicity. Our final logistic regression model found a significant independent association between age (adjusted OR=1.06), extrapulmonary involvement (adjusted OR=2.68), Löfgren's syndrome (adjusted OR=0.15) with outcome toward chronicity. CONCLUSIONS: In this first study searching for prognostic factors at diagnosis in a Northern Portuguese population, we found clinical prognosis factors that have been described in other populations that should be considered whenever sarcoidosis is identified

INTRODUCCIÓN: La sarcoidosis es una enfermedad granulomatosa multisistémica que afecta a los pulmones en más del 90% de los enfermos. Está asociada a un curso clínico variable y, considerando todas las formas diferentes de presentación de la enfermedad, hay una ausencia de marcadores de pronóstico clínico confiables que puedan predecir el resultado en el momento del diagnóstico. OBJETIVO: El objetivo de nuestro estudio fue investigar los factores pronósticos en el momento del diagnóstico en una población de enfermos con sarcoidosis del norte de Portugal. MÉTODOS: Se comparó un grupo de 110 enfermos con evolución crónica con 129 enfermos con resolución de la enfermedad teniendo en cuenta sus características clínicas, radiológicas y de laboratorio. RESULTADOS: Se encontró una asociación positiva entre las formas crónicas y el deterioro de la función pulmonar, el estadio radiológico II, la relación CD4/CD8 más baja y la enfermedad extrapulmonar. Ya el síndrome de Löfgren y la astenia tuvieron una asociación protectora significativa con la cronicidad. Nuestro modelo de regresión logística final encontró una asociación independiente significativa entre la edad (OR ajustada=1,06), la afectación extrapulmonar (OR ajustada=2,68), el síndrome de Löfgren (OR ajustada=0,15) y el resultado hacia la cronicidad. CONCLUSIONES: En este primer estudio de búsqueda de factores pronósticos en el momento del diagnóstico en una población del norte de Portugal, fueron encontrados predictores clínicos, que se han descrito en otras poblaciones que se deben considerar cada vez que se hace el diagnóstico de una sarcoidosis

Idiopathic CD4+ T lymphocytopenia: A case report.

Idiopathic CD4+ T lymphocytopenia (ICL) is a very rare immunodeficiency syndrome with an unexplained depletion of CD4+ T lymphocytes and no evidence of Human Immunodeficiency Virus (HIV) infection. Here we report a 29-year-old male patient who had severe ulcerative colitis with low level CD4+ count of 254 cells/mm3, and had no evidence of HIV or Human T cell Lymphotrophic virus type I or II infections. He had recurrent Candidiasis infection and his CD4 count was just 53 cells/mm3 after 3 months. The cause for the decline of CD4 T lymphocytes was unknown.

Disseminated cryptococcosis with granuloma formation in idiopathic CD4 lymphocytopenia.

Idiopathic CD4 lymphocytopenia (ICL) is a rare disease characterized by marked loss of CD4 T-cells without human immunodeficiency virus infection. CD4 T-cells play an important role in granuloma formation in cryptococcal infection. Thus far, among ICL patients, it has not been concluded definitely whether granuloma is formed or not. We report the case of a 39-year-old woman with ICL and disseminated cryptococcal infection with granuloma formation. She was referred to our department because of a lung mass, osteolytic lesion, and a subcutaneous mass identified on a computed tomography scan, and an elevated C-reactive protein level. Cryptococcus neoformans was isolated from the tissues. She also had marked CD4 lymphocytopenia (33 cells/µL), without human immunodeficiency virus infection. In a biopsy specimen of the lung mass, granulomas containing CD4 T-cells were observed. The cryptococcosis was treated with liposomal amphotericin B followed by fluconazole and she was found to be cured. The CD4 T-cell count was persistently low. This case showed that granulomas containing CD4 T-cells can be formed in ICL patients with cryptococcal infection despite very low CD4 T-cell counts.

Rare Concurrence of Two Congenital Disorders: Miller-Dieker Syndrome and T-Cell Lymphopenia.

Miller-Dieker syndrome (MDS; OMIM 247200) is a rare contiguous gene deletion syndrome associated with lissencephaly and characteristic facial dysmorphism. T-cell lymphopenia is an immunodeficiency disorder which can be early detected by newborn blood screening, and all live vaccines should be avoided. We report a 2.32-Mb microdeletion at chromosome 17p13.3p13.2 and T-cell lymphopenia in a 6-month-old male infant with MDS. This is, to our knowledge, the first description of these 2 conditions co-occurring in the same patient.

Idiopathic CD4 lymphopenia in a case of disseminated cryptococcosis with brain, vertebral spine and reproductive organ involvement.

Cryptococcosis is an opportunistic fungal infection commonly seen in HIV cases. We present a case of disseminated cryptococcosis with multiple non-continuous infective foci in a non-HIV, non-transplant case.

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.

Idiopathic CD4 lymphocytopenia: Pathogenesis, etiologies, clinical presentations and treatment strategies.

BACKGROUND: Idiopathic CD4 lymphocytopenia (ICL) is a rare condition characterized by an unexplained deficit of circulating CD4 T cells leading to increased risk of serious opportunistic infections. The pathogenesis, etiology, clinical presentation, and best treatment options remain unclear. OBJECTIVE: To describe the clinical presentation, treatment strategies, and outcome of patients with ICL seen in a single referral center. METHODS: In a retrospective study, from January 1993 to January 2014, the demographic characteristics, clinical presentation, and treatments of patients diagnosed with ICL were reviewed. RESULTS: Twenty-four patients (14 female [58%] and 10 male [42%]) were evaluated. The mean age was 45 ± 17.6 years (range 7-76 years). Mean CD4 and CD8 T-cell counts at the time of diagnosis were 119 ± 84/mm3 (range 4-294/mm3) and 219 ± 258/mm3 (range 7-630/mm3), respectively. Seventeen patients (71%) had opportunistic infections, 4 (17%) had malignancies, and 3 (13%) had unexplained demyelinating disease and neurologic problems. Most patients had normal levels of immunoglobulins. Thirteen patients had abnormally low to absent response to phytohemagglutinin, concanavalin A, and antigens (candida and tetanus). Three patients had resolution of warts and 1 had mycobacterial lung infection on interleukin-2 with increases in CD4 count. The 11 patients on trimethoprim and sulfamethoxazole had no further hospital admissions for infections. CONCLUSION: The pathogenesis of ICL remains unclear. Although only some patients are healthy, most patients present with opportunistic infections. There is no known standard treatment aside from prophylactic antibiotics.

Idiopathic CD4 Lymphocytopenia.

We report a 42 year old male who was an interesting case of "idiopathic CD4 lymphocytopenia"(ICL) in a non-HIV adult with-extra pulmonary tuberculosis along with the diffuse splenic calcification and whose symptoms improved with Antitubercular treatment. He was found to have low CD4 counts on two occasions.

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.

[A case of tuberculous meningitis associated with persistently reduced CD4+ T lymphocyte counts]. / Prípad tuberkulózní meningitidy provázené perzistujícím snízením CD4+ T lymfocytu.

A case history is presented of a 35-year-old man admitted to the hospital with tuberculous meningitis complicated by caseous necrosis of cervical lymph nodes and thrombosis of the left jugular vein. Another complication, malignant brain edema, appeared more than one year after discharge from hospital and was managed at the neurosurgery department. The most probable cause was a post-inflammatory obstruction of the cerebrospinal fluid pathways. A challenging finding, observed repeatedly while in hospital and at follow ups after discharge, was medium significant CD4+ T cell lymphopenia, with the lowest CD4+ T cell count of 308 cells/µl of peripheral blood. For this reason, the patient was screened several times for anti-HIV antibodies, but always with a negative result. Active tuberculous infection was considered as another possible reason behind persistent CD4+ T cell lymphopenia. However, imaging and laboratory analyses were not suggestive of tuberculosis. The patient is currently in good condition and his CD4+ T lymphocyte counts returned to normal at seven years of follow-up. It is underlined that patients after tuberculous meningitis need a long-term follow-up.

Disseminated cryptococcosis with caverno-oesophageal fistula in a case of idiopathic CD4+ T-lymphocytopenia.

Idiopathic CD4+ T-Lymphocytopenia is a rare immunodeficiency disorder characterised by significantly low absolute CD4 lymphocytes in absence of any viral infections. We present a case of Disseminated Cryptococcosis with Caverno- Oesophageal Fistula in a case of Idiopathic CD4+ T-Lymphocytopenia. 29 year old lady was referred to Institute in view of lung mass not responding to anti-TB treatment. Subsequently patient had developed headache. Radiological evaluation showed presence of ring enhancing lesion in the occipital region. On evaluation with Fibre-optic bronchoscopy, there was no evidence of malignancy or tuberculosis. Sputum showed presence and growth of Cryptococcus neoformans. Patient's investigations were negative for virus infection, with normal immunoglobulin levels. Her CD4 counts were 129 cells/mm3. Patient was treated with injectable antifungals. Patient developed a Caverno-oesophageal fistula which was confirmed on endoscopy and radiology. Patient was managed with percutaneous jejunal feeding (PEJ). Patient improved symptomatically with CD4 count of 475 cells/mm3.