I recently evaluated pt after 4th episode of "shingles". Pt is 40 yr old female with 4 episodes in the last 3-5 yrs or less. Pt with chicken pox at 5 yrs age. At 35 yrs age found to have a THYMOMA-no lymphoma. Hx of allergic rhinitis, 3 sinus infections in last one yr and 2 pneumonias in her entire life-NO hospitalizations or other health issues. MY work up included: normal CBC and diff, normal Igs and IgG subclasses, normal # of T and B cells and NK cells. Pneumococcal titers low but pt not aware of receiving pnuemovax with some apprehension about receiving it now. Complement C3 and C4, CH50-wnl. Good Diptheria and tetanus protective titers. Varicella Zoster Abs: IgM-neg, IgG 2.31 c/w "immunity" in the lab used.Pt HIV neg in 2009.

The patient recently called with now another episode of shingles. (FIFTH ONE) I referred her to infectious disease.

My question is in terms of immunology work up is there anything else that should be included?

Anergy panel?
Mitogen studies for T (and B) cells?

I read prior Ask the Expert questions on this and realize most people with recurrent H. zooster are immunocompetant-- but this is 5th episode in a 40 year old?

Are there other concerns to consider?

Thank you very much in advance for your expert opinion.


Thank you for your inquiry.

You are correct that most people with recurrent zoster are immunocompetent. To the best of my knowledge, those that do exhibit immunodeficiency have defects in the delayed rather than the humoral immune system. Therefore, further workup in regards to your patient would consist of an evaluation of delayed hypersensitivity, and this is usually done, as you mentioned, by employing a delayed hypersensitivity skin test panel (anergy panel) and in vitro proliferative responses to mitogens and antigens. Also cytokine production in response to mitogen and/or antigen stimulation or expression of surface markers after mitogen stimulation have been used. These tests, however, are specialty lab tests and more complex to perform. They are often normal if your cutaneous panel for delayed hypersensitive is normal.

Antigens commonly employed to test for delayed hypersensitivity include Candida, trichophytin, and PPD. Other antigens which have been used include tetanus, diphtheria, and streptococcus . Tests may be done using the Mantoux technique utilized for PPD testing, or with the Multitest device (1).

There is a very helpful discussion of delayed hypersensitivity skin tests in “ Bernstein et al: Allergy Diagnostic Testing, an Updated Practice Parameter, Annals of Allergy, Asthma, and Immunology, Volume 100, Number 3, Page S1-S148, March 2008.

One other point should be made is in regards to the fact that your patient has a thymoma.

The history of a thymoma is somewhat disturbing in that patients with thymoma, even in the absence of a lymphoma, can develop a deficiency in both the humoral and cellular limbs of immunity (Good syndrome). These patients usually present with hypogammaglobulinemia. However, in Good syndrome, there is also tendency toward opportunistic infections defended via cell-mediated immunity. These do include varicella-zoster as well as others such as herpes simplex, Candida, and cytomegalovirus.These patients usually present in their middle years. Therefore, in view of the fact that she does have a thymoma, it is conceivable that she may be in the early stages of this disorder. This is of note in that in such patients thymomas should be removed.

In summary, as noted, most patients with recurrent zoster are immunocompetent, but when defects of immunity are responsible, they often are associated with cell-mediated immunity. Cell-mediated immunity is best studied initially by applying delayed hypersensitivity skin tests as mentioned above, and then one can proceed to more complex measurements that require specialty laboratories and include in vitro responses to lymphocytes incubated with antigens.

Finally, of note in regards to your case is the presence of a thymoma, and this would alert you to possible early manifestations of Good syndrome.

Thank you again for your inquiry and we hope this response is helpful to you.

1. Maas JJ, et al. Journal of Infectious Diseases 1998; 178:1024-1029.

Phil Lieberman, M.D.

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