Thank you for your inquiry.
I initially misread your question - for reasons totally unknown to me - as indicating the C1 inhibitor was "normal" rather than "undetectable." I therefore originally misinterpreted your question, thinking we were dealing with an isolated C4 deficiency, a very rare event, and thus sent it to Dr. John Atkinson, a world recognized expert in complement, especially complement deficiencies.
It wasn't until I received Dr. Atkinson's very rapid and extremely helpful response that this error was called to my attention since, in his response sent to me by Dr. Hyon Ju Park, it was noted that both the C4 and C1 inhibitor levels were undetectable. Had I interpreted your question correctly, I would have answered your inquiry myself and clearly agreed with Drs. Park and Atkinson's superb response. Their response is copied for you below.
Unfortunately, I cannot explain why your patient is asymptomatic. It does call to our attention one more subtle element. As you know, patients with C1 inhibitor deficiency syndrome, especially with classical hereditary angioedema, oftentimes develop a serpiginous nonpruritic rash which can be confused with urticaria. I am of course not sure whether your patient's rash is of this nature, but if it does not itch and is not elevated, contrary to my original comment about urticaria, it may be related to the C1 inhibitor deficiency syndrome. I personally do not think any therapeutic action is indicated as long as he is asymptomatic.
Finally, I echo Drs. Atkinson and Park's statement about obtaining a C2 and possibly obtaining C1 inhibitor gene sequencing. I suppose there are other cases of asymptomatic patients with C1 inhibitor deficiency, but I have never seen one nor have I noted one in the literature.
We would greatly appreciate a follow-up on your patient if you notice any change in symptoms.
Thank you again for your inquiry.
Phil Lieberman, M.D.
Response from Drs. Atkinson and Park:
In terms of the 33 y.o. Asian male with undetectable levels of both C4 and C1 inh, he likely has either acquired or hereditary angioedema without any clinical manifestations. His rash is likely unrelated although pictures and details regarding frequency and duration of episodes and treatment response would be helpful. Obtaining a C2 antigenic level and a test for C1 inh antibodies would be important. If C2 is also low, the patient should have his C1 inh gene sequenced. We can certainly assist with the sequencing if needed.
Hyon Ju Park, M.D.
John Atkinson, M.D.