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.

Introduction

CD4 lymphocytes are immunologically important as they confer immunity status of the body and its depletion, causes immune deficiency. Normally the CD4 count ranges from 500 to 1500 cells/mm3, when their count falls below 500 cells/mm3 people are at great risk for opportunistic infections. Their counts serve as a prognostic marker to predict the risks in AIDS conditions.

The drop in CD4 count to 300/mm3 or <20% of total T cells with no evidence of Human Immunodeficiency Virus (HIV), Human T-Lymphotrophic Virus (HTLV) and absence of any other immunodeficiency's is poorly understood. This unusual immune defect condition is characterized as Idiopathic CD4 lymphocytopenia (ICL).[1] ICL with unexplained deficiency and unknown etiology leads to serious opportunistic infections.[23] Studies have revealed different heterogeneous cause and manifestation for this syndrome.

Low CD4 T-cell in ICL could be accredited due to decreased production or increased destruction of cells, tissue sequestration, or combination of all these. Though supportive evidence for each of these explanations has been reported in few cases, it is not possible to interpret whether the findings are the cause of ICL or/are consequences of the lymphopenia itself.[4]

Candidiasis is one of the most common fungal opportunistic infection recorded in HIV patients. These infections are commonly observed in pregnancy, diabetes mellitus, and in other immunodeficiency conditions. Here, we report one such rare ICL case from Karnataka, South India with unknown etiology. A male patient who had severe ulcerative colitis with Candida infection, presented low CD4+ T- count with no risk of HIV, HTLV, or other immunodeficiency.

Case History

A 29-year-old male was hospitalized with history of toxic megacolon a complication of ulcerative colitis and had complaints of 10–15 episodes of blood associated loose stools per day in a week. He gave a history of weight loss, non-consistent abdomen pain, and unable to eat in a period of two months. He was nondiabetic and had no other malignancies or history of any surgery/hospitalization. On investigation it was found that he had ulcerative colitis with pancolitis of grade IV activity with mild ascites and no generalized lymphadenopathy and organomegaly.

Blood investigation revealed low hemoglobin of 7.8 g/dl, PCV 26.2%, RBC 3.91, MCV 67, MCH 19.9, MCHC 29.8, and increased RDW 15.4, reticulocyte count 3.4, total count 8750 cells/mm and platelet count of 5.56 lakh/mm3. Peripheral smear showed microcytic hypochromic anemia with thrombocytosis. Biochemical findings reported increased C-reactive protein (BIO – Immunoturbidometry) 21.8 mg/l and decreased sodium (ISE direct) 130 mEq/L and amylase (CNP-Triose) activity 13 U/L. The CD4+ T-cell counts performed by flow cytometry (Becton Dickinson) was 296/mm3 which is less than Centers for Disease Control and Prevention’s guidelines.

Chest X-ray was grossly normal with no evidence of tuberculosis. X-rays erect abdomen showed multiple air fluid levels, suggestive of intestinal obstruction. Stool occult blood was negative, and stool microscopic examination showed plenty of budding yeast cells which were germ tube negative. The yeast isolated was Candida haemulonii by VITEK.

On admission patient was treated conservatively, received steroids for a short course of 3 days, but he did not respond to the treatment. Later he developed colonic perforation and underwent laparotomy-subtotal colectomy with ileostomy. He had post-operative surgical site infections. Ziehl – Neelsen staining of biopsy and pus were negative. Microscopic examination of pus revealed no evidence of acid bacilli infection; on culturing Candida, Klebsiella pneumonia, and Streptococcus were identified. The CD4 count when measured after a gap of 3 months was found to be much declined i.e., 56/mm3.

Additional investigations were performed to test any underlying disorder such as HIV, HTLV, lymphoma, leukemia. HIV tests were repeatedly negative to both HIV–1 and 2. Serological tests for Hepatitis B and C virus were negative, HTLV was ruled out by PCR. Peripheral blood smear and biopsy of large intestine examinations revealed absence of leukemia and lymphoma. No other complications were found in patient history.

Discussion

ICL is a heterogeneous condition in which the clinical presentations range from asymptomatic to life-threatening opportunistic infections, similar to as those found in patients with lymphopenia and HIV. Malignancies which relate to opportunistic pathogens with an oncogenic potential, autoimmune diseases, Cryptococcal, Candidiasis, Cytomegalovirus, nontuberculous mycobacterium infections and progressive multifocal leukoencephalopathy are also observed in ICL.[56] The syndrome is usually found in association with co-infections, but it is unclear whether infections trigger or their consequences lead to ICL.[7] Recent studies have revealed that the genetic basis of ICL could be due to the defects in the magnesium transporter gene-(MAGTI), mutation of recombination activating gene 1 or mutation in the Uncoordinated gene-(Unc119).[489] Therefore understanding the molecular basis of this immunodeficiency could lead to diagnose and improve the condition, and may also help to develop new therapeutic measures to improve the CD4 count.

CD4 count was measured in present case as a part of the study of Candidiasis infected cases with ethical clearance and clear consent. This case of ulcerative colitis was diagnosed as ICL because of severe and persistent lymphocytopenia condition with no exact cause. Candida may not be the cause but, it could have been one of the notable infections described for asymptomatic CD4 lymphocytopenia.[6] As per Dina et al. findings, 16.2% of ICL patients were associated with Candida infections.[10]

CD4 counts are usually determined in HIV patients and not in non-HIV; hence, most of the ICL cases goes undetected. As per the review, diagnosing ICL is difficult due to unknown cause or possibilities of genetic mutations. Efforts are needed to review cases of opportunistic infections in which CD4 count declines with unknown cause, because mortality probability remains high in recurrent infections.

ICL is a rare syndrome and differential diagnosis should be included when there is unexplained opportunistic infections and suspected depletion of T-cell count. Management of ICL could be done by treating the opportunistic infections using appropriate antimicrobials and strategies that increase CD4 counts and boosts the immune function. Understanding the genetics and immunopathogenesis of this heterogeneous condition may guide to establish safe therapy to ICL patients and avoid increased risk of morbidity and mortality.

Declaration of patient consent

The authors certify that appropriate patient consent was obtained.

Financial support and sponsorship

This work was supported by the University Grant Commission [No. F.15-1/2015-17/PDFWM-2015-17-KAR-36705 (SAII).

Conflicts of interest

There are no conflicts of interest.