Thank you for your recent inquiry.
In essence, your patient has isolated IgM deficiency. We have had several entries regarding isolated IgM deficiency. For your convenience, I have copied one of these below.
As you can see, there is little one can do except for antibiotic prophylaxis and therapy. There is no need to work up the elevated IgA further since you have ruled out monoclonality.
Thank you again for your inquiry and we hope this response is helpful to you.
Hypogammaglobulinemia M with Normal Levels of Other Immunoglobulins
I have a 79 year old Caucasian patient with a history of 9 life threatening pneumonias and recurrent urinary tract infections in the year of 2007. Her only lab abnormalities are:
- severe IgM deficiency with a serum level of 10 mg% and normal serum IgG, IgA and IgE
- serum immune electrophoresis with a monoclonal IgG lambda gammopathy peak but with a normal bone marrow aspirate and biopsy and a good hematology consult without answers. No evidence for multiple mieloma with a normal bone survey.
What to do next? IVIG Rx?
I will tell you what I know about isolated IgM deficiency.
Selective immunoglobulin M deficiency is a rare form of hypogammaglobulinemia. The mechanism behind this dysregulation is unknown. Since the appearance of isolated IgM deficiency defies our normal concept regarding isotype switching (IgM to other classes), its appearance is at this time a paradox.
Although the exact frequency of selective IgM deficiency is unknown, it probably occurs in less than 0.03% of the general population.
Patients with selective IgM are clearly susceptible to overwhelming infection with encapsulated bacteria such as strep pneumonia, neisseria meningitis, and haemophilus influenza. This condition has been associated with a number of other problems including malignancies, chronic gastrointestinal symptoms, and autoimmune disease.
There appears to be no gender predilection, and this phenomenon has been encountered in infants as well as older adults.
Patients with isolated IgM deficiency can be asymptomatic, manifest with symptoms primarily related to malignancy or autoimmune disease, or can present with recurrent infections as with your patient. Malignant neoplasms including multiple myeloma, sarcomas, and leukemias have all been found in association with isolated IgM deficiency. Rheumatoid arthritis, Hashimoto’s thyroiditis, autoimmune hemolytic anemia, and systemic lupus have also been found with isolated IgM deficiency.
Miscellaneous conditions such as Crohn’s disease, chronic diarrhea of unknown cause, and idiopathic splenomegaly have also been described.
Unfortunately there is no specific treatment for isolated IgM deficiency. IgM, as you know, is not contained in intravenous immunoglobulin preparations. However, some patients with isolated IgM have shown defective IgG responses to immunization (e.g., pneumococcus), and therefore the assessment of an immunization response is indicated.
I suggest that you get baseline titers for pneumococcal serotypes, tetanus, and influenza, and then repeat these titers after immunization with Pneumovax, tetanus toxoid, and influenza vaccine. If there is a defective response, especially to Pneumovax, then the patient may be a candidate for intravenous immunoglobulin replacement therapy.
Prophylactic and therapeutic antibiotics are of course indicated, and there is at least one report of fresh frozen plasma given during severe infections (Zaka-Ur-Rab: Indian Pediatrics 2005; 42:961-962).
In summary, I would suggest the following:
1. Monitoring of the monoclonal gammopathy because this patient certainly could be in an early stage of multiple myeloma.
2. Assessment of immune response to antigens as noted above, and consideration of replacement with intravenous immunoglobulin if the response is defective.
3. Consider the use of prophylactic antibiotics and, of course, rapid treatment of respiratory and other types of infections.
I hope this is of help. Please feel free to contact us if you have further questions.
Phil Lieberman, M.D.