MADRID, Spain—Systemic lupus erythematosus (SLE) and common variable immunodeficiency (CVID) are at opposite poles, immunologically speaking, but a growing number of CVID cases is being reported in lupus patients. Because SLE develops first, rheumatologists should monitor immunoglobulin profiles in lupus patients and should consider CVID in all lupus patients who have recurrent sinopulmonary infections in the absence of lupus activity and/or immunosuppressive treatment, according to a new study in the February issue of Seminars in Arthritis & Rheumatism.¹

"Recurrent infections in a patient with SLE activity, apart from SLE activity and/or immunosuppresive treatment, must alert the physician to possible CVID and treatment with gammaglobulins may be highly effective," conclude researchers led by Mónica Fernández-Castro, MD, of the Hospital Universitario Puerta de Hierro, Madrid, Spain.

Two polar extremes of immune reactivity

Dr. Fernández-Castro and colleagues described the cases of two patients with SLE and CVID and identified 16 other patients through a literature review. Overall, 89% of CVID patients were females who had a mean age of 23.8 years at the onset of SLE. CVID developed within the first 5 years after the lupus diagnosis in half these patients, the study showed. All patients had been treated with corticosteroids and 72% had also received immunosuppressive therapy. The most frequent symptom was sinopulmonary infections. SLE disease activity decreased after the development of CVID in 67% of patients. Most patients (89%) were treated with gammaglobulin therapy. The most notable immunological feature was a reduced number or percentage of B-cells in 60% of patients.

CVID in lupus may be caused by an intrinsic B-cell deficit or by an extrinsic factor with an effect on B-cell maturation, they hypothesize. Whether these two seemingly opposite disorders coexist or if the CVID is a complication related to the SLE or SLE treatment is not fully understood.

"The findings of an apparent association between these two disorders in this small group of patients should alert physicians to a new long-term consequence of lupus," study authors conclude.

Telltale signs of CVID in lupus

"Although SLE-associated CVID is uncommon, due to its potentially fatal outcome, it should be considered in any SLE patient with hypogammaglobulinemia (at least 2 standard deviations below the mean for age in serum concentration of IgG and IgA), poor or absent response to immunization (two-fold or less increase in antibody titer), and acute, chronic, or recurrent infections, specifically pneumonia bronchitis, sinusitis conjunctivitis, and otitis," Dr. Fernández-Castro writes.

Because all of the identified patients were diagnosed with lupus before CVID, the authors call for immunoglubulin measurements in SLE patients.

Measure immunoglubulin before chemo

"CVID in lupus is a rare thing—even in my population," said Robert Lahita MD, PhD, FACP, FACR, FRCP, professor of medicine at Mount Sinai Medical School, in New York, and chairman of medicine at the Jersey City Medical Center, in New Jersey. A lupus specialist, Dr. Lahita, the editor of Systemic Lupus Erythematosus, added "If you have chronic sinusitis or some suggestion of immunodeficiency, you should be tested for immunoglubulin levels."

Dr. Lahita said that currently he only runs a panel of immunoglubulins on patients in whom he is unable to make a straightforward lupus diagnosis.

"I probably would still treat the SLE patient the same way," he said. "If you are intending to give a lupus patient tremendous amounts of chemotherapy like cyclophosphamide [Cytoxan®, Neosar®] I think you should test for immunodeficiency. If you give Cytoxan and knock out bone marrow, you are going to also enhance the patient's risk of getting infected, since they don't have much immunoglubulin lying around."

References

1. Fernández-Castro M, Mellor-Pita S, Citores MJ, et al. Common variable immunodeficiency in systemic lupus erythematosus. Semin Arthritis Rheum. 2007;36:238-245.