Cytomegalovirus Colitis in Primary Hypogammaglobulinemia With Normal CD4+ T Cells: Deficiency of CMV-Specific CD8+ T Cells.

CMV colitis has been reported in immunocompromized patients with severe deficiency of CD4+ T cells and T cell functions. In this study we present an extensive immunological analysis in a patient with primary hypogammaglobulinemia and CMV colitis who had normal numbers of CD3+T, CD4+T and CD8+T cells, and normal T cell proliferative responses to mitogens and recall antigens. Naïve (TN), central (TCM), and effector (TEM) memory subsets of CD4+ and CD8+ T cells, Granzyme+ and Perforin+ CD8+ T cells, PD-1+ T cells, CD4 Treg, CD8 Treg, and CMV tetramer specific CD8+ T cells were analyzed with specific antibodies and isotype controls using multicolor flow cytometry. CD8 TEM, Granzyme+ and Perforin+, and PD-1 CD8+T cells were increased, whereas CD8 TN and CD8 TCM cells were decreased in the patient as compared to controls. CMV tetramer+ CD8+ T cells were decreased in the patient. These data demonstrate that a deficiency of CMV-specific CD8+ T cells even in the presence of normal CD4+ T cell numbers and normal T cell functions may predispose patients with primary hypogammaglobulinemia to CMV colitis.

Rituximab and immune deficiency: case series and review of the literature.

BACKGROUND: As the indications and use of rituximab continue to expand, the reports of long-term effects of anti-CD20--mediated B-cell depletion on the immune system accumulate. OBJECTIVE: We report a group of patients with immunodeficiency who were treated with rituximab and present their immunologic data. METHODS: A retrospective chart review identified patients with immunodeficiency who received rituximab for treatment of their primary disease and required immunoglobulin replacement therapy (IGRT). Pre-IGRT immunoglobulins, specific antibodies, B-cells, and B-cell phenotype were recorded and analyzed. RESULTS: We identified 11 patients with immunodeficiency who received rituximab and required IGRT. Two of these patients were diagnosed with common variable immunodeficiency before rituximab treatment. Nine other patients had hypogammaglobulinemia and did not achieve an adequate response to polysaccharide vaccine. There was a significant delay in B-cell recovery. B-cell phenotypes identified predominantly naive B cells in the blood of these patients with significant decrease in switched and memory B cells. CONCLUSION: There are patients with persistent B-cell dysfunction long after rituximab treatment was discontinued. Some of these patients required IGRT. These patients should be distinguished from patients with primary immunodeficiency diseases. Routine baseline B-cell numbers and serum immunoglobulin levels before starting immunomodulatory therapy are required to help distinguish primary immunodeficiency diseases from secondary rituximab-induced, transient, and, at times, prolonged immune suppression. Periodic monitoring is prudent to identify immune recovery. Post-rituximab B-cell phenotyping may help identify the patients who will develop persistent immune dysfunction caused by an unidentified underlying disease or the prolonged effect of rituximab treatment.

Variation in the depth of excision of melanoma: A survey of US physicians.

OBJECTIVE: To assess current practices and recommendations of US physicians regarding depth of excision for melanomas of varying histologic thicknesses. DESIGN: A 2-page, 13-question survey of depth of excision practices for the treatment of melanoma was developed and distributed. SETTING: Both private and academic settings. PARTICIPANTS: A total of 1184 US physicians (1000 dermatologists and 184 melanoma specialists) were sent the survey. The 184 melanoma specialists included dermatologists, oncologists, and surgeons working in pigmented lesion clinics. MAIN OUTCOME MEASURES: Depth of excision practices reported for melanomas of varying histologic thicknesses and comparison of treating physician groups. Results were tabulated, and descriptive frequencies were used to describe demographics and survey responses. RESULTS: The final study analysis included 498 completed surveys. The overall response rate was 45% (498 of 1097 [1184 total respondents - 87 ineligibles]). The response rate for the specialists was 63% (115 of 183 [184 total respondents - 1 ineligible]), and for nonspecialist dermatologists it was 43% (383 of 892 [1000 total respondents - 108 ineligibles]). Specialists were more likely to practice in an urban setting than were nonspecialist dermatologists (78% vs 46%) (P < .001). Fifty-eight percent of nonspecialist dermatologists reported more than 400 patient visits per month compared with only 16% of specialists (P < .001). While specialists reported fewer patient visits per month, 51% reported diagnosing over 20 invasive melanomas in the previous year compared with 11% of nonspecialist dermatologists. There was no significant difference in excision depth reported among the specialties for melanoma in situ (P = .15). For invasive melanoma, significant differences were observed among treating groups, with the greatest incongruence reported for thin invasive melanoma (<0.50 mm, P = .02; 0.50-0.75 mm, P < .001; and 0.76-1.00 mm, P < .001). Specialist nondermatologists consistently reported excising more deeply than specialist dermatologists and nonspecialist dermatologists. More specialist nondermatologists report excising to the fascia for thin invasive melanoma than do both specialist and nonspecialist dermatologists. For thicker melanomas (>1.00 mm), differences in excision depths among treating physician groups decreased: most physicians in each group reported excising to the fascia. CONCLUSIONS: There is considerable variation among physician groups with regard to depth of excision practices for the treatment of melanoma. Given the current lack of clinical data available, studies assessing depth of excision and patient outcomes are needed to better define our surgical management of melanoma.