Does rituximab (rituximab) cause CD4 depletion in a patient with idiopathic CD4 lymphocytopenia and latent tuberculosis, who is also being treated for pemphigus vulgaris?

Rituximab and CD4 Depletion

Rituximab does NOT directly deplete CD4+ T cells—it specifically targets CD20+ B cells, not T cells. However, in your patient with pre-existing idiopathic CD4 lymphocytopenia and latent tuberculosis being treated for pemphigus vulgaris, rituximab poses substantial infection risks that require careful consideration.

Mechanism of Action and Cell Targeting

• Rituximab is a chimeric monoclonal antibody that targets CD20, a B cell-specific surface antigen, leading to selective B cell depletion for 6-12 months 1, 2.
• CD20 is NOT expressed on T cells (including CD4+ T helper cells), plasma cells, or hematopoietic stem cells 3.
• B cell depletion occurs in 70-80% of patients, with circulating B cells becoming undetectable within days and remaining depleted for 6-12 months 2, 3.

Indirect Effects on T Cell Populations

While rituximab does not directly target CD4+ T cells, research demonstrates important indirect effects:

• In pemphigus vulgaris patients, rituximab causes a significant decrease in autoreactive CD4+ Th1 and Th2 cells for 6-12 months, while overall CD3+CD4+ T lymphocyte counts remain unaffected 4.
• This represents a presumably specific downregulation of disease-specific CD4+ T helper cells, not generalized CD4 depletion 4.
• The overall count of CD4+ T lymphocytes and tetanus toxoid-reactive CD4+ Th cells remain stable during rituximab therapy 4.

Critical Safety Concerns in Your Patient

Your patient's pre-existing idiopathic CD4 lymphocytopenia creates a high-risk scenario that warrants extreme caution:

Infection Risk Profile

• Serious infections (Grade 3-4) occur in less than 5% of NHL patients, but bacterial infections occurred in weeks following rituximab in pemphigus patients 3, 5.
• In pemphigus vulgaris specifically, 2 of 3 patients in one series experienced bacterial infections in the weeks following rituximab 5.
• The 2012 British Association of Dermatologists guidelines report that among 8 pemphigus patients treated with rituximab, two died from nosocomial pneumonia (6 weeks post-treatment) and bacterial sepsis (2 years post-treatment), and one child developed persistent hypogammaglobulinemia 1.

Special Considerations for Low CD4 Counts

• The 2024 EHA-ESMO guidelines explicitly state that rituximab should be used with caution in patients with CD4 count <50 cells/μL and may need to be delayed 1.
• This recommendation comes from HIV-associated lymphoma guidelines but applies to any patient with severe CD4 lymphocytopenia 1.

Latent Tuberculosis Reactivation Risk

• Screening for hepatitis B is mandatory before rituximab, as reactivation can be fatal 6.
• While the provided guidelines focus on hepatitis B, the principle of opportunistic infection reactivation applies equally to tuberculosis in immunocompromised patients.
• Your patient's latent TB combined with baseline CD4 lymphocytopenia creates compounded risk for TB reactivation.

Monitoring Requirements if Proceeding

If rituximab is deemed necessary despite these risks:

• Obtain baseline immunoglobulin levels before initiating therapy 2.
• Monitor complete blood count at 2-4 month intervals during treatment for cytopenias 2.
• Consider PCP prophylaxis during and following rituximab treatment, particularly with triple immunosuppression or additional risk factors 6.
• Monitor for late-onset neutropenia, which can occur 42+ days after the last dose 3.

Clinical Pitfalls to Avoid

• Do not assume that normal total lymphocyte counts mean adequate CD4 counts—specific CD4 monitoring is essential in your patient.
• Do not overlook the risk of hypogammaglobulinemia, which occurred in 14% of NHL patients and can be persistent 3, 1.
• Progressive multifocal leukoencephalopathy is a rare but fatal complication requiring vigilance 2.

Alternative Considerations

Given your patient's baseline immunocompromise, consider:

• Optimizing conventional immunosuppression before escalating to rituximab.
• Ensuring adequate TB prophylaxis is established and therapeutic before any B cell depletion therapy.
• The standard pemphigus protocol achieves 89% complete remission when rituximab is combined with short-term prednisolone, but this was not studied in patients with pre-existing severe immunodeficiency 6.