[CIS PIDD] [cis-pidd] Puzzling case of ? underlying defect in fungal immunity?

Mon Jul 14 09:12:33 EDT 2014

Thanks. I don't think this has been pursued as you say.  I'll have to check when I return to UCLA and see what the doctors have done.

Andy Saxon
UCLA

-----Original Message-----
From: Seppänen Mikko [mailto:Mikko.Seppanen at hus.fi]
Sent: Monday, July 14, 2014 3:07 AM
To: CIS-PIDD
Subject: [cis-pidd] VS: Puzzling case of ? underlying defect in fungal immunity?

Dear prof Saxon,

As a suggestion only (You may have ruled this out already, if so - my apologies): have You tested for aspergillus IgE-antibodies? Chronic necrotizing/cavitary/..) pulmonary aspergillosis (old name semi-invasive aspergillosis), possibly in an HLA-B27 positive individual getting a reactive EN, perhaps also previous apical scarring caused by previous TBC??

At least prof David Denning in GB would be able to test a wide range of Aspergillus IgE-antibodies (most labs only do A. fumigatus-IgE-Abs, like ours), only very occasionally A. niger has been documented as a probable cause. You will probably know the US labs Yourself. HRCT often develops into a radiologically very typical picture, but can be misleading at first and not all patients get the cavitary form.

Yours,

Mikko

dos Mikko Seppänen, LKT
Immuunipuutosv-o, HYKS

Mikko Seppänen, MD, PhD, Associate professor/Senior Lecturer Specialist in Internal Medicine and Infectious Diseases Senior Consultant, Physician in charge (PIDD)

Immunodeficiency Unit
Division of Infectious Diseases
Department of Medicine
Helsinki University Central Hospital
Hospital District of Helsinki and Uusimaa Aurora Hospital, Ward 4-2 and Outpatient Clinic P.O.Box 348
FI-00029 HUS, Helsinki
FINLAND
phone +358 9 47175923, fax +358 9 47175945

-----Alkuperäinen viesti-----
Lähettäjä: Saxon, Andy M.D. [mailto:ASaxon at mednet.ucla.edu]
Lähetetty: 10. heinäkuuta 2014 23:47
Vastaanottaja: CIS-PIDD
Aihe: [cis-pidd] Puzzling case of ? underlying defect in fungal immunity?

I am asking help in
? diagnosis and tests to establish
? suggested tests for underlying immune defect ? any good ideas as it doesn't resonate with me.
All input greatly appreciated

CASE
The subject is a 59 year old woman who has not seen an immunologist yet. I was contacted about her and will be referring her for evaluation. I have no brilliant insight into possible mutations etc that would lead to fungal infection (if that is what it truly is) and look like this.  Does she have a longstanding subtle = immunodeficiency, some weird polymorphism of zap70 or other thing that could effect the CD8 and lead to increased fungal infection? Or what?
.
*       Abrupt onset in the Fall 2010: night sweats, fatigue, erythema nodosum, left clavicle and bilateral knee pain, elevated ESR (50 range)

*       Oct 2010 Abnormal Chest XRay followed by Chest CT revealed bilateral apical scaring, two large RUL masses (>3 cm in size) with visceral pleural involvement at onset, smaller/nodes in left lung.

*       Oct-Dec 2010  Multiple attempts at diagnosis included two CT guided lung biopsy, bronchoscopy, mediastinoscopy with lymph node biopsy.
*       Pathology: chronic lymphoplasmacytic inflammation with occasional necrotizing granulomata with focal collection of eosinophils *         (GMS and AFB stains negative, culture negative)
*       Bronchoalveolar lavage grew Aspergillus niger (? Contaminant)
*       Lung/lymph node biopsies did not show any fungi

*       December 2010 Right upper lobectomy planned but patient started on voriconazole pre-op (for Aspergillus "colonizer") and systemic symptoms resolved. However severe transaminitis precluded continued voriconazole therapy. Once liver function normalized itraconazole was started in 2/11. Ultimately lung lesions reduced to less than 1.5 cm in size.  Presumptive diagnosis: granulomatous, fungal lung disease
*       Extensive ID evaluation negative for organism
*       February 2011 to May 2013 On itraconazole -symptoms controlled well.  ESR 15 range, CRP <0.3. Stopped itraconazole after more than 2 years of therapy.

*       June-July, 2013 Within 2 months of stopping itraconazole, developed tenosynovitis of wrist and ankle, elevated ESR to 50 range and CRP to 1.8-2.
*       August 2013 Started fluconazole 8/for presumptive chronic fungal infection (coccidiodomycosis).  Continued symptoms and elevation of ESR and CRP despite changing to itraconazole in February 2014.  Developed recurrence of night sweats, fatigue, E nodosum.  Wrist synovial biopsy showed plasma cells/lymphocytes.

*       June 2014 Recent evaluation included immunoglobulins and lymphocytes:
*       Immunoglobulins were all in normal range -IgE 25 IU/mL, IgM low normal 46 (44-277) IgG and IgA mid normal range
*       B cells normal
*       T cells: CD8 lymphopenia
*       absolute CD8 was 98  (lab normal 255-1090)
*       absolute CD3 was 506 (lab normal 841-2402)
*
OTHER:
White cells and all the routine tests in this regard normal even during her illness except the liver damage from Vorconazole, did not spike white cells or neutrophils at any time ANA RF, cANCA, Myeloperoxidase Ab, Proteinase 3 Ab, ACE, Cyclic citrulin  ALL NORMAL/NEG NEGATIVE  HIV, MTB quantiferon gold neg X 2,  Cocci (IGA and IGM, CF and TP), HepBs, HepC neg, Cryptococcal, Blasto & Histo serology, Aspergillus ab "neg" (I'm not sure exactly what test was done, ppt, Elisa or what)

*       On reflection, patient recalls recurrent history of pneumonia/bronchitis starting age 2-3 and continuing into teen years.  At that time (in the late 1950's) she received monthly shots of immunoglobulin for about 10 years.  There was no unusual infection history during her adult life until 2010.

Andy Saxon, MD
Professor and Emeritus Chief, CIA, UCLA

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