History
Patients may be asymptomatic, with a decreased IgM level noted during the investigation of other diseases, such as malignancies or autoimmune diseases.
Prolonged or life-threatening infections also occur, especially in infancy. Recurrent infections (eg, sinusitis and pneumonia) are often caused by encapsulated bacteria, and pneumococcal sepsis has been reported. [10] Infections with gram negative bacteria are also more common than in normal individuals, especially with Pseudomonas aeruginosa.
Associated disorders or symptoms may include atopic or chronic dermatitis, impetigo, [16] wheezing, and diarrhea. Patients may have a history of splenectomy.
Physical
Failure to thrive may be present, due at least in part to frequent infections. Other associated signs may include features of dermatitis, allergic rhinitis, wheezing, and splenomegaly, as well as those of other primary conditions associated with secondary SIgM deficiency, such as malignant or autoimmune disorders.
Causes
The cause of SIgM deficiency is unknown, and no clear pattern of inheritance has been suggested. The stability of the finding of selective deficiency of IgM, vs progression to deficiency of other immunoglobulin isotypes, has not been well characterized.
Patients with malignant neoplasms (eg, clear cell sarcoma, Bloom syndrome, promyelocytic leukemia), autoimmune diseases (eg, rheumatoid arthritis, Hashimoto thyroiditis, systemic lupus erythematosus, autoimmune hemolytic anemia), infections (eg, Brucella), or those given immunosuppressive agents may develop secondary SIgM deficiency. [17, 18]
Two case reports of epidermodysplasia verruciformis (caused by human papillomavirus) associated with SIgM deficiency are reported. One of these patients developed squamous cell carcinoma. [19, 20]
As cited by Zaka-ur-Rab, associations exist between SIgM deficiency and gastrointestinal conditions, including Crohn disease, chronic diarrhea, lymphoid nodular hyperplasia, Whipple disease, and splenomegaly. [21]
Infants with permanent congenital hypothyroidism were shown to have undetectable or lower concentrations of IgA and lower concentrations of IgM than normal controls. [22]
A report of 13 multiple myeloma patients in a phase 2 study showed that the 7 patients who received rituximab following autologous stem cell transplantation developed severely depressed levels of IgM that were persistent with continued rituximab therapy. When compared to the 6 myeloma patients who had received autologous stem cell transplantation without rituximab, not only were IgM levels significantly decreased, but those in the rituximab group experienced far more infections, including 21 cases of pneumonia, 2 cases of sepsis, and one death during the first 12 months. [23]
Three cases of 22q11.2 deletion syndrome associated with SIgM deficiency have been reported. The diagnoses were made at ages 9, 10, and 14 years. All 3 patients presented with recurrent otitis media, velopharyngeal insufficiency, speech delay, and learning disability, and 1 patient also had atrial septal defect/ventricular septal defect. [24, 25]
A 13-year-old African American boy with local lymph node involvement showed, after diagnosis and even 4 years after the chemotherapy, a low and decreasing level of both peripheral memory B cells and blood IgM-positive B lymphocytes. This case report highlights a possible association between SIgM deficiency and chronic CD30+ cutaneous lymphoproliferative disorder. [26]
