I have a 59 year-old patient with CVID, mod persistent bronchial asthma and allergies, and is questioning why she has recurring thrush.

Her medicines include:
0 steroids for 1 year
0 antibiotics for 3 years
Alvesco 160mg 1 puff twice a day
Foradil 1 capsule twice a day
Singulair 10 mg
Zyrtec 10 mg qd
Hizentra weekly

A two week course of Diflucan gives temporary relief. Is there a relationship between the two? She obviously is not on any meds to cause. No h/o diabetes.


Thank you for your inquiry.

There are two plausible reasons that your patient has recurrent thrush:

1. Patients with common variable immunodeficiency (CVID) oftentimes have associated T cell defects (see abstracts copied below). These can result in defective cell-mediated immunity.

2. Candida albicans is an infrequent, but well recognized complication, of orally inhaled corticosteroids. In clinical trials, Candida albicans occurred in 32 of 3,038 patients (Source: Package insert for Alvesco).

Thank you again for your inquiry and we hope this response is helpful to you.

Clin Infect Dis. 2009 Nov 1;49(9):1329-38. doi: 10.1086/606059.
Late-onset combined immune deficiency: a subset of common variable immunodeficiency with severe T cell defect.
Malphettes M1, Gérard L, Carmagnat M, Mouillot G, Vince N, Boutboul D, Bérezné A, Nove-Josserand R, Lemoing V, Tetu L, Viallard JF, Bonnotte B, Pavic M, Haroche J, Larroche C, Brouet JC, Fermand JP, Rabian C, Fieschi C, Oksenhendler E; DEFI Study Group.
Collaborators (79)
Fieschi C, Malphettes M, Galicier L, Fermand JP, Asli B, Viallard JF, Jaccard A, Hoarau C, Hoarau Y, Bérezné A, Mouthon L, Karmochkine M, Schleinitz N, Durieu I, Nove-Josserand R, Chanet V, Le-Moing V, Just N, Salanoubat C, Jaussaud R, Suarez F, Hermine O, Solal-Celigny P, Hachulla E, Sanhes L, Gardembas M, Pellier I, Tisserant P, Pavic M, Bonnotte B, Haroche J, Amoura Z, Alric L, Thiercelin MF, Tetu L, Adoue D, Bordigoni P, Perpoint T, Sève P, Rohrlich P, Pasquali JL, Soulas P, Couderc JL, Catherinot E, Giraud P, Baruchel A, Deleveau I, Chaix F, Donadieu J, Tron F, Jacquot S, Larroche C, Blanc AP, Masseau A, Hamidou M, Kenny G, Morisset M, Millot F, Fain O, Borie R, Debré P, Schmitt C, Le Garff-Tavernier M, Faideau B, Mkada H, Mouillot G, Garnier JL, Théodorou I, Marcelin AG, Calvez V, Rabian C, Carmagnat M, Fieschi C, Malphettes M, Vince N, Boutboul D, De Gouvello A, Gardeur A, Gérard L.
1Département d'Immunologie, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France.
Background: Common variable immunodeficiency (CVID) is a primary immune deficiency defined by defective antibody production. In most series, a small proportion of patients present with opportunistic infections (OIs).
Methods: The French DEFI study has enrolled patients with primary hypogammaglobulinemia and allows a detailed clinical and immunologic description of patients with previous OIs and/or at risk for OIs.
Results: Among 313 patients with CVID, 28 patients (8.9%) presented with late-onset combined immune deficiency (LOCID), defined by the occurrence of an OI and/or a CD4(+) T cell count <200 x 10(6) cells/L, and were compared with the remaining 285 patients with CVID. The patients with LOCID more frequently belonged to consanguineous families (29% vs 8%; P = .004). They differed from patients with CVID with a higher prevalence of splenomegaly (64% vs 31%), granuloma (43% vs 10%), gastrointestinal disease (75% vs 42%), and lymphoma (29% vs 4%). Even on immunoglobulin substitution, they required more frequent antibiotics administration and hospitalization. Lymphocyte counts were lower, with a marked decrease in CD4(+) T cell counts (158 x 10(6) vs 604 x 10(6) cells/L; P < .001) and a severe defect in naive CD45RA(+)CCR7(+)CD4(+) T cell counts (<20% of total CD4(+) T cells in 71% of patients with LOCID vs 37% of patients with CVID; P = .001). The CD19(+) B cell compartment was also significantly decreased (20 x 10(6) vs 102 x 10(6) cells/L; P < .001).
Conclusions: LOCID differs from classic CVID in its clinical and immunologic characteristics. Systematic T cell phenotype may help to discriminate such patients from those with CVID. Identification of this phenotype should result in a more fitted diagnostic and therapeutic approach of infections and could provide insights for genetic diagnosis

Allergol Immunopathol (Madr). 2009 Jan-Feb;37(1):14-20.
Immunophenotypic profile of T cells in common variable immunodeficiency: is there an association with different clinical findings?
Lanio N1, Sarmiento E, Gallego A, Carbone J.
Author information
1Immunology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Background: A system based on the B-cell phenotype has recently been proposed to classify patients suffering from common variable immunodeficiency (CVID). Immunophenotypic T-cell abnormalities have also been correlated with clinical findings, although they have never been used in classification strategies.
Objective: To simultaneously assess T and B-cell subset abnormalities in CVID patients and their relationship with clinical findings. To identify potential immunophenotypic T-cell abnormalities that could be further evaluated in multicenter studies.
Patients and Methods: Peripheral blood lymphocytes from 21 CVID patients and 21 healthy donors were stained for T and B-cell subsets, analyzed by flow cytometry, and correlated with clinical characteristics.
Results: Patients classified as MB0 (CD19/CD27+ < 11 %) showed higher percentages of CD4/ CD45RA (87 % vs 67 %, p = 0.028) and lower percentages of CD8/CD45RA+CCR7+ (10 % vs 26 %, p = 0.028) and CD4/CD25+ T-cells (36 % vs 62 %, p = 0.034) than MB2 patients. Even though our cohort was small, we observed a higher prevalence of distinct clinical complications of CVID in patients with B and T-cell abnormalities. Nonmalignant lymphoproliferative disorders and IgG hypercatabolism were more frequently observed in MB0 patients. A higher prevalence of splenomegaly was observed among CVID patients with increased levels of CD4/CD45RA, activated CD4/CD38+DR+, CD8/DR+, and CD8/CD38+ T-cells, as well as in those with lower percentages of CD4/CD45RA+CCR7+ and CD4/CD25+ T-cells. Lymphoproliferative disorders were more prevalent among CVID patients with higher CD4/CD45RA percentages.
Conclusion: The study of T-cell subsets warrants further evaluation as a potential tool to better identify CVID patients with distinct clinical profiles.

Phil Lieberman, M.D.

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