[PAGID] 22q11 deletion and granulomas

[MacGinnitie, Andrew]

Jack Initial CT is below and shows mild enlargement of mediastinal and axillarly lymph nodes.  No splenomegaly.



Follow up roughly 2 and 6 months after initial shows increased nodular size, but no change in lymph nodes.  Spleen on latest CT (about 3 weeks ago) is "mildly enlarged, unchanged"



There are multiple pulmonary nodules of various sizes

scattered throughout both lungs most marked in the lower lobes with

some being pleural based. The nodules have varying morphology, a few

beingwell defined, with most having shaggy less well-definedborders.

The sizes of the nodular-like abnormalities ranges from several mm to

2 cm. No cavitation or  calcification is identified in these

nodules.Scattered increased interstitial lung markings and areas of

ground-glass opacificationin the lower lobes are present with some of

the ground glass opacities contiguous with the more focal pulmonary

lesions. There is nopleural effusion or pneumothorax.



There are several mildly enlarged retrocrural lymph nodes with the

largest measuring approximately 1 cm in transverse diameter. There

are bilaterally mildly enlarged uniformly enhancing axillary lymph

nodes with the largest measuring 16 mm in transverse dimension. No

mediastinal or hilar adenopathy or mass is present.



There is right aortic arch with an aberrant left subclavian artery.

There is a bridging vein with an anomalous subaortic left BCV and a

persistent left SVC draining into a dilated coronary sinus. No

definite additional cardiovascular anomaly is detected. The pulmonary

arteries are unremarkable with no suggestion of pulmonary embolus.

The trachea, mainstem and branch bronchi are widely patent.



Limited sections through the upper abdomen show normalliver, no focal

lesions or intrahepatic biliary ductal dilatation. The visualized

spleen is normal.





Andrew J. MacGinnitie MD PhD

Assistant Professor of Pediatrics

Division of Pulmonary Medicine, Allergy and Immunology

Children's Hospital of Pittsburgh

45th Street and Penn Ave 15201

andrew.macginnitie at chp.edu

412/692-8903 (office) 412/692-8499 (fax)



-----Original Message-----
From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Routes, John
Sent: Tuesday, July 06, 2010 4:52 PM
To: pagid at list.clinimmsoc.org
Subject: Re: [PAGID] 22q11 deletion and granulomas



Agree with importance of  excluding infectious cause, but if the nodular pattern was present in the fall of last year on CXR and in view of the lack of infectious symptoms, I doubt this is infectious. Can you give a more detailed description of the chest CT? Is there diffuse adenopathy with hilar/mediatinal nodes? Is splenomegaly present? I would get full PFTs (plethysmography) and perform a 6 minute walk to get baseline studies of pulmonary physiology and treat with corticosteroids if you are unable to find any concrete evidence of infection.

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: "Chinen, Javier" <jxchinen at texaschildrens.org>

Reply-To: "pagid at list.clinimmsoc.org" <pagid at list.clinimmsoc.org>

Date: Tue, 6 Jul 2010 13:57:29 -0500

To: "pagid at list.clinimmsoc.org" <pagid at list.clinimmsoc.org>

Subject: Re: [PAGID] 22q11 deletion and granulomas



These ‘sterile’ granulomas are always a challenge.

I would first establish degree of T cell deficiency found within the 22q11.2 spectrum by measuring naïve CD4 T cells, and also look at memory B cells to help assessing humoral immunity. Secondary immunodeficiencies may need be in consideration: immunosuppresion for Evans syndreom, HIV infection in adolescents.



Besides clinical history, it may be helpful to look at specific antigens, and Fungitell (though not good for Crypto and Blastomyces) and Aspergillus galactomannan looking for negatives that would help decision on steroids. We also send tissue for mycobacteria PCR (though no high yield if AFB not seen)

Donors for IgG products are supposed to be healthy, though we and others have found antibodies for infectious diseases at diagnostic titers in scid patients receiving IVIG before immunoreconstituion.



Javier



________________________________



From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of MacGinnitie, Andrew

Sent: Tuesday, July 06, 2010 7:57 AM

To: pagid at list.clinimmsoc.org

Subject: [PAGID] 22q11 deletion and granulomas



I’d appreciate any input on the following patient, who I met for the first time last week



15 year old girl with 22q11.2 diagnosed by FISH at age 9 secondary to hypocalcemia, heart defects (VSD and PDA) and Evans syndrome (autoimmune thrombocytopenia and anemia).



She has also had severe lichen planus primarily on the legs that has not responded to topical steroids.  She had one lesion that became superinfected and needed 6 months of therapy by a wound clinic



Over the last few years she has had several CXR diagnosed pneumonias which have typically responded to antibiotics as well as some sinus infections.  Another immunologist started her on subcutaneous IgG replacement 9 mos ago based on the history of pneumonias and low normal IgG (564) with normal IgA and IgM.  She had an adequate response to Tetanus but responded to 1/14 pneumococcal serotypes (no  vaccination).  Interestingly, she feels the SCIG has improved her lichen planus.



Last fall she had cough, shortness of breath and chest pain that she attributed to another pneumonia.  A course of azithromycin didn’t help and a repeat CXR showed a nodular pattern, that on reexamination was present on the first CXR.



She got CT, brochoscipy  with BAL and then transthoracic biopsy that revealed granulomas but no organisms were visualized or grew in culture.  The pathologists initially thought these were likely infectious but on reexamination don’t feel they can rule out sarcoidosis although they don’t think the lesions are typical.

A PPD was negative



The lesions are being followed by CT and seem to be slowly getting worse although clinically she is well.  ID felt that serologies for possible fungal causes like Cryptococcus, blastomycosis and histoplasmosis would be uninterpretable due to IgG replacement



A literature search turned up an abstract at the AAAAI several years ago of 3 patients with 22q11 and sarcoid but not much else



I wonder if anyone has seen a similar case or has other ideas.

I also wonder if anyone knows if there are significant antifungal titers in IgG products.



Given the diagnostic uncertainty and possible infectious etiology  we are hesitant to treat with steroids unless we have too.



Thanks



Andy



Andrew J. MacGinnitie MD PhD

Assistant Professor of Pediatrics

Division of Pulmonary Medicine, Allergy and Immunology

Children's Hospital of Pittsburgh

45th Street and Penn Ave 15201

andrew.macginnitie at chp.edu

412/692-8903 (office) 412/692-8499 (fax)





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