58 year-old male with recurrent blastomycosis and abnormal immune workup. He was referred by ID after his third episode of blastomycosis.

In 11/2010, he was diagnosed with cutaneous blastomycosis treated with itraconazole for 12 months. Eight months after treatment completion, he had recurrent cutaneous lesions and biopsies showed blastomycosis for which he was treated with itraconazole for about 18 months from 9/2012 to 3/2014. Two months after completing this course, he was diagnosed with pulmonary blastomycosis after he developed headaches, fever, mild cough, and sweats and chest CT showed bilaterally pulmonary nodules which were biopsied. He was started on itraconazole again and immune workup was checked by ID.

He had normal immunoglobulins (IgA 335, IgG 978, IgM 98), low absolute lymphocytes at 533 (850-3900), low absolute CD4 count of 201, low RBC 3.84, high platelets of 444, WBC of 5900, and lymphocytes of 500. Total lymphocyte count measured on CBC during the months of May and June, 2014 has ranged from 300 (5/12), 200 (5/14), 700 (5/19), 500 (5/20), 300 (5/21), and more recently 500 (6/5), and flexitest showed low total lymphocytes at 421 with low CD19 cells 80 (19%), low CD3 cells 282 (67%). Inflammatory markers such as ESR are increased and ANA has always been negative. I did not see any HIV testing in our system; however I was told that HIV testing was negative. Imaging does not show lymphadenopathy. He denies a history of other infections such as skin, sinopulmonary, urinary, or other infections aside from three episodes of blastomycosis.

He is an avid gardener and spends time in the vegetable garden and with fresh compost pile, and spreading mulch. In April 2014 since completing his most recent itraconazole, he began working with the compost again.

Notably, he was diagnosed with sarcoidosis in 1995 after biopsy was done “in the chest for enlarged lymph nodes” although records were not available. In 2003, symptoms increased and he was treated with a tapering course of prednisone over 5 years until 2009. He has travelled to Mexico, South Africa, Germany, and Canada in the past 8 years. blastomycosis.

It seems itraconazole is effective in treating his infections as symptoms improve, however he has recurrent blastomycosis which could be an opportunistic infection in the setting of immune deficiency. It seems he needs to be worked up for other causes of CD4 lymphocytopenia including confirmation of HIV status and assesement of cellular immunity. Before ordering further labs, I want to ask what further blood work would you recommend in the analysis of his immune deficiency. It seems less likely, but would 5 years of prednisone be enough to suppress him immune system years later. Also we plan to look for secondary causes of lymphocytopenia including bone marrow evaluation and malignancy workup. Please advise on this interesting case as any input would be welcome and helpful.


Thank you for your inquiry.

With rare exception, the immune deficit in recurrent blastomycosis is defective cell-mediated immunity (1-4). Therefore, the primary tests to evaluate the immune system in a patient with recurrent blastomycosis are tests to assess cell-mediated immunity. A ready source for these tests is Table 4 on Page S6 of the Parameter on Immunodeficiency published in the Annals of Allergy, Asthma, and Immunology, Volume 94, May 2005 (first author is Bonilla). You may obtain this reference free of charge online by going to the Joint Council of Allergy, Asthma, and Immunology website and clicking on "Parameters."

As you will see from looking at this table, skin tests and in vitro lymphocyte stimulation testing are the basic tests that are usually employed in this assessment. We have a number of entries on our "Ask the Expert" website regarding the skin tests that can be used for assessment of cell-mediated immunity. You can access these by clicking here and entering "cell mediated immunity" in the search box.

The more sophisticated tests noted in the aforementioned Table 4 are usually done at immunodeficiency centers, but some of them can be ordered from specialty laboratories.

Also, as you know, sarcoidosis is associated with defective cell-mediated immunity and is probably a predisposing factor contributing to the infection.

Unfortunately, the tests for the assessment of cell-mediated immunity would basically confirm what you have found already, and would be expected to be abnormal in view of this patient's course and his sarcoidosis. It would not, however, rule out any other underlying disease, and your pursuit for other causes of the lymphocytopenia is indicated.

Finally, I do not believe that five years of prednisone alone would "permanently depress" his immune system. There would be recovery after cessation of this drug. Thus I think the sarcoidosis is a far more likely culprit.

Along this line, you might be interested in an Archives of Dermatology article (June 2006; Volume 142(6):795-797) entitled "Cutaneous blastomycosis: a clue for reassessing the recent diagnosis of pulmonary sarcoidosis."

Thus, in summary, my guess is that your patient has defective cell-mediated immunity which can be assessed by delayed hypersensitivity skin tests and in vitro stimulation studies with mitogens and antigens as described in the Practice Parameters mentioned above. I believe that the defective cell-mediated immunity is related to his sarcoidosis, and not due to his previous prednisone therapy. However, simply identifying this, of course, does not alter the treatment, and in this regard, there is an excellent reference that can be obtained free of charge online. It is the Clinical Practice Guidelines for the Management of Blastomycosis: 2008 update by the Infectious Diseases Society of America. Lead author is Chapman. I have copied below a link to that website.

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

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Robert W Bradsher Jr, MD

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Robert W Bradsher Jr, MD

Clinical Practice Guidelines for the Management of Blastomycosis: 2008 Update by the Infectious Diseases Society of America

1. J Allergy Clin Immunol 1971; 47(1):17-22.
2. J Allergy Clin Immunol 1971; 46(1):40-46.
3. The American Review of Respiratory Disease 1978; 118(2):325-334.
4. Infection and Immunity 1980; 78:393.

Phil Lieberman, M.D.

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