[PAGID] Delayed post-BMT lung disease

[Routes, John]

Richard
Assuming the TLC was normal, the pattern of airflow limitation suggests a mixed restrictive obstructive lung disease (reduced FEV1 with equivalent reduction in FVC is consistent with a restrictive defect, but an increased RV is typically seen in obstructive disease). Bronchiolitis obliterans (BO) is obstructive and one should see an increased TLC, increased RV and reduced FEV1/FVC ratio.  BO is a known late complication of BMT (about 10% of cases overall) and is frequently missed on transbronchial bx and only reliably diagnosed with an open lung biopsy. It is interesting that your patient has responded to corticosteroids in the past as BO is usually resistant to steroid treatment. A variety of other agents (macrolides, other immunosuppressives) have been used for BO with mixed success. Based on the data you have given us,  I wonder if there is something else going on here such as cryptogenic organizing pneumonia (COP) (also known as BOOP) another late complication of BM transplantation. Unlike BO, COP is typically steroid responsive and other immunosuppressives have also been used to treat this disorder such as cyclophosphamide. Did the latest CT scan show any evidence of patchy ground glass abnormalities? Were expiratory CT images obtained?
Jack


John M. Routes, MD
Chief, Section of Allergy and Clinical Immunology
Professor of Pediatrics, Medicine, Microbiology and Molecular Genetics
Department of Pediatrics
Children's Hospital of Wisconsin
Medical College of Wisconsin
9000 W. Wisconsin Ave.
Milwaukee, WI  53226-4874

Phone: 414-456-4802; 414-266-6997
Fax: 414-456-6487 (Clinical)
Fax: 414-456-6323 (Laboratory)
Email: jroutes at mcw.edu




________________________________
From: Richard Wasserman <drrichwasserman at gmail.com>
Reply-To: "pagid at list.clinimmsoc.org" <pagid at list.clinimmsoc.org>
Date: Tue, 20 Jul 2010 08:07:04 -0500
To: "pagid at list.clinimmsoc.org" <pagid at list.clinimmsoc.org>
Subject: Re: [PAGID] Delayed post-BMT lung disease

Complete pulmonary function testing showed increased residual volume as the only abnormality not picked up by standard spirometry (coordinate decrease in FEV1 and FVC. DLCO was normal. Pulmonologist (part of the lung transplant group) believes that this is a recurrence of bronchiolitis obliterans despite the negative biopsy. Her last episode, which occurred one year post transplant in 2001, did not respond to prednisone 40mg bid for two week but did respond to solumedrol 10mg/kg once a week. Are there other suggestions? Note that the patient has had somewhat difficult to control hypertension.
Thanks for your input.
Richard Wasserman
Dallas

On Fri, Jul 9, 2010 at 5:38 PM, Sergio Rosenzweig <srosenzweig at garrahan.gov.ar> wrote:
Hi Richard,
Is the patient AIRE mutation positive? (bronchiolitis obliterans has been described in APECED patients, probably autoimmune), is she fully grafted or a mixed chimera?
Sergio

Sergio D. Rosenzweig, MD, PhD
Chief, Infectious Diseases Susceptibility Unit
Laboratory of Host Defenses, NIAID, NIH
10 Center Dr., Bldg. 10, CRC 5W-3888
Bethesda, MD 20892-1456
Phone (301) 451 8971
Fax (301) 451 7901
Cell (240) 361 7617
Pager 102 10678
srosenzweig at niaid.nih.gov

Disclaimer: The information in this e-mail and any of its attachments is confidential and may contain sensitive information. It should not be used by anyone who is not the original intended recipient. If you have received this e-mail in error please inform the sender and delete from your mailbox or any other storage devices. National Institute of Allergy and Infectious Diseases shall not accept liability for any statements made that are senders own and not expressly made on behalf of the NIAID by one of its representatives.

>>> Richard Wasserman <drrichwasserman at gmail.com> 07/08/10 8:01 PM >>>

A now 27 year old woman with chronic mucocutaneous candidiasis and multiple
endocrinopathy (thyroid, parathyroid, adrenal, ovary?) received a match
sibling transplant in 1997 and now has dyspnea and abnormal pulmonary
function tests.

She has RSV during the transplant (first identified prior to marrow
infusion) but did quite well. Approximately nine months post-transplant she
developed Zoster that responded well to treatment. One year and a few days
after transplant she developed respiratory symptoms and a significant fall
in FEV1 and FVC. CT report showed:
*Ct chest  4/21/99*

*History: possible interstitial lung disease. Bone marrow transplant
patient.*

*Technique: helical 7-mm images are obtained through the cheat at a 1-to-1
pitch without intravenous contrast. Then, an expiratory and an inspiratory
image was obtained at 2-cm increments 1-mm high-resolution cuts to judge
areas of air trapping or interstitial disease.*

*Findings: no definite adenopathy can be seen on the soft tissue windows.
Standard 7-mm lung windows show no focal infiltrate, edema, pleural
thickening, or effusion. There is mild prominence of peribronchial lining.*

*High-resolution images, inspiratory and expiratory films, fail to reveal
focal or localized areas of air trapping. There is peribronchial thickening
with some mild suggested bronchiectasis in the right upper lung, superior
segment of the lower lobes. There is slight granular haze of the lungs
without discrete reticular nodular pattern which is nonspecific. There is no
"beading" or discrete retraction or fibrosis noted. The mild bronchiectatic
change appears more prominent compared to the study of february 1997.
Peribronchial cuffing was noted at that time as well, no central
intraluminal mucous plug can be seen.*

*Impression:*

*1. Nonspecific pzribronchial cuffing with wild suggestion of bronchiectasis
can be associated with asthma or reactive airway disease but is otherwise
nonspecific. High-resolution images suggest some slightly gray parenchymal
changes diffusely without nodularity also nonspecific. Focal nodular
deposits of suspected graft-versus-host disease cannot be conclusively
demonstrated on this ct study.*
*She was bronchoscoped:*
*transbronchial biopsies obtained on the day prior to admission demonstrated
bronchiolitis obliterans with active interstitial pneumonitis. No viral
inclusions, acid-fast bacilli, fungi, or malignant cells were identified.
Immunostains for Pneumocystis carinii and cytomegalovirus were negative.
Viral, bacterial, fungal and AFB cultures were negative.*

She was treated with pulse Solumedrol and IVIG and resolved with return of
FEV1 and FVC to her premorbid levels and clearing of her chest CT with no
residual abnormality.

In the intervening years she has had mild persistent asthma but has not
needed oral steroids. Antibody production and mitogen and antigen responses
have been normal. There has been normal recovery from respiratory viral
infection (she's a school teacher), no candida and rare need for
antibiotics. She has had hypertension. In March, 2010 she presented with
shortness of breath.

December 08 - FEV1 106% of predicted, FVC 97% of predicted
December 09 - FEV1 94% of predicted, FVC 85% of predicted
March 10 - FEV1 68% of predicted, FVC 64% of predicted
June 10 - FEV1 72% of predicted, FVC 64% of predicted

*Repeat bronchoscopy in March 2010:*
*MICROSCOPIC DIAGNOSES: Transbronchial biopsies of lung: Multiple biopsies
are present containing adequate bronchial and alveolar parenchymal tissue
for evaluation; minimal subacute bronchitis is present unaccompanied by
granulomas or viral inclusions; the alveolar tissues are histologically
unremarkable; a histologic explanation for the patient's worsening
lung function is not identified; special stains for acid-fast bacilli and
fungi are negative, as are *immunostains for Cytomegalovirus and
Pneumocystis carinii; a special stain for amyloid was, likewise, negative.*
*
*
*Right bronchial washings (cell block and cytospin preparations, Pap and
Wright stains): Benign respiratory columnar cells and pulmonary macrophages
are present within a clean inflammatory background; no viral inclusions or
malignant cells are identified; special stains for acid-fast bacilli and
fungi are negative, as are *immunostains for*
*Cytomegalovirus and Pneumocystis carinii; all stains exhibit appropriately
reactive controls.*
*
*
*Culture for bacteria, virus, fungus and AFB grew only alpha hemolytic
streptococci. She was treated with minocycline without benefit.*

At this time she is mildly dyspnea at rest but has no exercise tolerance.
Pulmonology has no suggestions for further diagnosis or treatment.

I would appreciate any thoughts on this patient.

Richard L. Wasserman, MD, PhD
DallasAllergyImmunology
7777 Forest Lane, Suite B-332
Dallas, Texas 75230
Office (972) 566-7788
Fax (972) 566-8837
Cell (214) 697-7211




--
Richard L. Wasserman, MD, PhD
DallasAllergyImmunology
7777 Forest Lane, Suite B-332
Dallas, Texas 75230
Office (972) 566-7788
Fax (972) 566-8837
Cell (214) 697-7211