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ISSN: Print -2349-0977, Online - 2349-4387

 Table of Contents  
Year : 2015  |  Volume : 2  |  Issue : 1  |  Page : 38-39

Idiopathic CD4 lymphocytopenia presenting as cryptococcal meningitis

Department of Medicine, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India

Date of Web Publication26-Oct-2015

Correspondence Address:
Dr. Pranav Ish
Goel Bhawan, 4/56, Mehrauli, New Delhi - 110 030
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2349-0977.168253

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How to cite this article:
Ish P, Singh H, Anuradha S, Dewan R. Idiopathic CD4 lymphocytopenia presenting as cryptococcal meningitis. Astrocyte 2015;2:38-9

How to cite this URL:
Ish P, Singh H, Anuradha S, Dewan R. Idiopathic CD4 lymphocytopenia presenting as cryptococcal meningitis. Astrocyte [serial online] 2015 [cited 2021 Mar 8];2:38-9. Available from: http://www.astrocyte.in/text.asp?2015/2/1/38/168253

Cryptococcal meningitis is a common opportunistic infection in human immunodeficiency virus (HIV) positive patients especially at CD4 count <100 cells/mm 3. Unusually, cryptococcal meningitis can also present in HIV negative patients who have some other identifiable cause for immunosuppression such as immunosuppressive drugs, diabetes, and malignancies such as leukemia. In the absence of any identifiable risk factors, patients with CD4 counts <300 are labeled to have Idiopathic CD4+-lymphocytopenia (ICL) – an extremely rare clinical condition. Such patients also have increased risk of all opportunistic infections similar to those found in other severely immunocompromised patients. Only a few reports of this disease entity have been published from India. We present the case of ICL in a 30-year-old woman and review the literature.

A 30-year-old lady resident of Saharanpur, Uttar Pradesh presented to the Medicine Emergency with complaints of fever for 2 months, a headache for 2 months, nausea, and vomiting for 1 month, and altered sensorium for 4 days.

There was no history of seizures, blurring of vision, ear discharge, or any focal deficit. There was no history of alcohol consumption, diabetes mellitus, malignancy, receiving any chemotherapy, or any other immune suppressive medications or known HIV infection. The patient had a past history of antitubercular treatment (ATT) intake 5 years back for pulmonary tuberculosis and was currently on category II ATT for past 4 months prescribed empirically by a private practitioner.

On examination, the patient was conscious but not oriented to time, place, and person with Glasgow Coma Score (GCS) 12. She was thin built, dehydrated, febrile with a temp of 100.2 F in the right axilla. Her pulse rate was 88/min regular, blood pressure was 102/68 mm of Hg, and her respiratory rate was 16 breaths/min. Pallor was present, and there was no cyanosis, icterus or clubbing; her jugular venous pressure was not raised, and there were no dilated veins in the neck.

Central nervous system examination revealed neck rigidity. There was no motor deficit, and the patient was moving all four limbs. All deep tendon reflexes were within normal limits, and bilateral plantar responses were extensor. Her GCS was 12. Fundus examination was suggestive of papilledema. The rest of the physical examination was unremarkable. The investigations of the patient are summarized in [Table 1].
Table 1: Laboratory Investigations

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A guarded lumbar puncture was carried out and the cerebrospinal fluid (CSF) opening pressure was raised. The results of CSF analysis are summarized in [Table 2]. CSF analysis for Mycobacterium tuberculosis by cartridge based nucleic acid amplification test was negative. Test for cryptococcal antigen by latex agglutination was positive. The patient was tested for HIV infection by enzyme-linked immunosorbent assay based test, and results were negative. The CD4 count of the patient was 235 cells/mm 3 and her CD3 count was 446 cells/mm 3. Test for HIV was repeated after 6 weeks which was negative. Repeat CD4 count of the patient was 260 cells/mm 3. A magnetic resonance imaging of the brain revealed communicating hydrocephalus with diffuse cerebral atrophy [Figure 1].
Table 2: CSF Analysis

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Figure 1: Axial Flair showing dilation of ventricles suggestive of hydrocephalus.

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The patient was started on induction treatment with a combination of injection amphotericin B (1 mg/kg body weight) and intravenous fluconazole (800 mg/day) for 2 weeks. A strict watch on hydration status, urine output, and daily monitoring of kidney function tests and serum potassium was carried out. The patient improved symptomatically and regained sensorium on the 4th day of therapy. The intracranial pressures were controlled with intravenous mannitol and repeat lumbar punctures were not needed. The patient was gradually allowed all oral feeds and was built nutritionally. Peripheral smear of blood and bone marrow aspirate were normal and not suggestive of any atypical cells. She was later switched to consolidation treatment with oral fluconozole 400 mg/day for 8 weeks to be followed up by maintenance treatment with 200 mg/day oral fluconazole.

  Discussion Top

Idiopathic CD4+-cell lymphocytopenia (ICL) is defined by persistent CD4+-cell lymphopenia in the absence of infection with HIV-1 or any other cause of the immunodeficiency, with CD4+-cell counts below 300 cells/microL.[1]

ICL is a disorder of unknown etiology. Initially believed to be of viral etiology, research has recently focused on identifying abnormalities in various aspects of immune function. ICL is characterized by an increased predisposition to opportunistic infections. The typical clinical manifestations of ICL include cryptococcal, mycobacterial, and other opportunistic infections, malignancies, and autoimmune disorders. These conditions are all believed to result from immune dysregulation.[2] Due to the rarity of this condition, no specific guidelines exist for prophylaxis, monitoring, or treatment.[3] Therefore, the management is based on the experience with HIV treatment where such opportunistic infections are common.[4] A high index of suspicion is necessary for their identification, so that early treatment can be started for opportunistic infections.

There are few case reports from India. In these reports also, patients presented with diseases such as cryptococcal meningitis and tuberculosis. Sharma et al. reported a case of refractory cryptococcal meningitis with ICL with a CD4 count of 203 cells/mm 3 in Chandigarh.[5] Two cases of ICL with dermal candidiasis and disseminated tuberculosis infection were reported in Delhi by Mukherjee et al.[6] For improving CD4 counts, treatment with interleukin-2 has been suggested.[3] However, in view of the paucity of data, there are no recommendations on how to treat such patients, and due to unclear pathophysiology, it still remains a challenge to the practice of modern medicine.

Hence, in immunocompetent patients who do not have HIV infection or other known immunosuppressive conditions that develop unusual opportunistic infections, a possibility of idiopathic lymphocytopenia must be entertained.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Smith DK, Neal JJ, Holmberg SD. 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. N Engl J Med 1993;328:373-9.  Back to cited text no. 1
Ahmad DS, Esmadi M, Steinmann WC. Idiopathic CD4 lymphocytopenia: Spectrum of opportunistic infections, malignancies, and autoimmune diseases. Avicenna J Med 2013;3:37-47.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
Augustine R, Khalid M, Misri ZK, Hegde S. Idiopathic CD4+ T-lymphocytopenia – A diagnostic dilemma. J Assoc Physicians India 2010;58:45-7.  Back to cited text no. 3
Loongo DL, Fauci AS, Kasper DL, Hauser S, Jameson JL, Loscalzo J, et al. Principles of internal medicine. Harrison's Principles of Internal Medicine. 18th ed., Ch. 202. New York: McGraw-Hill. 2012. p. 1650-2.  Back to cited text no. 4
Sharma A, Lal V, Modi M, Khurana D, Bal S, Prabhakar S. Idiopathic CD4 lymphocytopenia presenting as refractory cryptococcal meningitis. Ann Indian Acad Neurol 2010;13:136-8.  Back to cited text no. 5
[PUBMED]  Medknow Journal  
Mukherjee A, Lodha R, Kabra SK. Idiopathic CD4+ T-cell lymphocytopenia. Indian J Pediatr 2009;76:430-2.  Back to cited text no. 6


  [Figure 1]

  [Table 1], [Table 2]

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