[CIS PIDD] [cis-pidd] Recurrent Sepsis Syndrome

Fri May 8 09:56:35 EDT 2015

I will put my 2 cents in  — we have a patient with Clarkson’s disease who had 3 separate admissions for “ sepsis” with high WBC, severe hypotension, needed pressers,  ICU stay x3,   but there was no bug and no immune thing we could find.

He is older and has a monoclonal protein in blood ( most do) and the theory is that this is capillary leak syndrome due to some vascular dysfunction triggered  in some way.  the Rx is IVIG in high dose monthly..

On May 7, 2015, at 5:50 PM, Richard Wasserman <drrichwasserman at gmail.com<mailto:drrichwasserman at gmail.com>> wrote:

Thank you for your suggestions.

The patient was evaluated by Dr. Pitlock about three years ago and the studies were negative or normal.

He is not monocytopenic.

I am working on a mitochondrial evaluation.

Does the group think it would be helpful to measure cytokine when he is well as a baseline and then at presentation? If so, which cytokines?

Thanks,
Richard Wasserman
Dallas

On Fri, May 1, 2015 at 7:29 AM, Kumar, Ashish <Ashish.Kumar at cchmc.org<mailto:Ashish.Kumar at cchmc.org>> wrote:
Richard,
This may totally out of the ballpark, but since you mentioned infections and edema, and all these other weird things, GATA2 comes to mind. Look at the monocyte count and you'll know. I can't explain the seizures but everything else you described was present in my first patient with this disease, all due to systemic mycobacterial infection.
Ashish

Ashish Kumar, MD, PhD
Cancer and Blood Diseases Institute
Division of Bone Marrow Transplantation and Immune Deficiency
Cincinnati Children's Hospital Medical Center
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-----Original Message-----
From: Boyce, Thomas G., M.D. [mailto:Boyce.Thomas at mayo.edu<mailto:Boyce.Thomas at mayo.edu>]
Sent: Thursday, April 30, 2015 4:31 PM
To: CIS-PIDD
Subject: RE: [cis-pidd] Recurrent Sepsis Syndrome

Richard,

We have a patient with an undiagnosed mitochondrial disease who develops severe sepsis everytime she gets influenza.  We keep her on oseltamivir during the flu season.  She gets it on other occasions as well.  I will forward your case to Sean Pittock here and see if he has other thoughts as suggested by Mel.

Tom

Thomas G. Boyce, MD, MPH
Pediatric Infectious Diseases and Immunology Mayo Clinic
email: boyce.thomas at mayo.edu<mailto:boyce.thomas at mayo.edu>
phone: 507-255-8464<tel:507-255-8464>
fax: 507-255-7767<tel:507-255-7767>

-----Original Message-----
From: Mel.Berger at cslbehring.com<mailto:Mel.Berger at cslbehring.com> [mailto:Mel.Berger at cslbehring.com<mailto:Mel.Berger at cslbehring.com>]
Sent: Thursday, April 30, 2015 1:42 PM
To: CIS-PIDD
Subject: Re: [cis-pidd] Recurrent Sepsis Syndrome

I can't easily tie it all together, but have two suggestions:

1. Treat acute episodes with IL-1 or IL-6 antagonist

2. Repeat work up for dysautonomia- particularly antibodies to ganglionic acetylcholine receptors. Actually, I would suggest contacting Sean Pittock or Vanda Lennon at the Mayo clinic and get them to test for every neuronal antibody they have. They are describing new antibodies mediating Neuro syndromes almost as fast as we are defining new PID genes,

Mel Berger

Sent from my iPhone

On Apr 30, 2015, at 12:28, Richard Wasserman <drrichwasserman at gmail.com<mailto:drrichwasserman at gmail.com><mailto:drrichwasserman at gmail.com<mailto:drrichwasserman at gmail.com>>> wrote:

Colleagues:

I need help with a 23 yo male admitted for the 6th episode of culture negative sepsis syndrome since he had H1N1 pneumonia requiring mechanical ventilation about one year ago. The episodes are characterized by high fever but no focal findings. Hypotension develops in the first 24-36 hours and requires fluid resuscitation and pressors. Initial WBC ~4500 and left shifted. Increases to ~10,000 in the first few days. CRP increases to ~60. He is always treated with multiple antibiotics at presentation and blood cultures, fungal blood cultures, respiratory cultures and respiratory virus assays have been negative. He improves over three to five days and is discharged. The episodes are not temporally related (either before or after) to his IGIV.

I apologize for the length of his history but he has had multisystem disorders that I don't understand and may stimulate a productive thought.

Immunologic - At age 4, he an evaluation for recurrent infection (see below) that showed low normal immunoglobulin concentrations and poor response to pneumococcal polysaccharide vaccine.  After prophylactic antibiotics failed, he improved with IGIV. At age 14 IGIV was stopped and he deteriorated. Reevaluation showed hypogammaglobulinemia. IGIV was restarted and bacterial infections have been a minor, occasional problem.

Infection - Chronic otitis as an infant evolved to recurrent sinusitis and conjunctivitis. Bacterial chest infections have been rare. There have been many episodes of Candida esophagitis related to steroid and antibiotic use. At age 14, he had a respiratory tract infection the resulted in symptoms that were only partially bronchodilator responsive. Hospitalization was prolonged. One year later, he developed parainfluenza 3 pneumonia and was hospitalized. At age 22, he developed H1N1 pneumonia and required mechanical ventilation. He has returned to baseline of limited activity tolerance.

Respiratory - There is long standing cough, chest tightness and shortness of breath that responds partially to high dose bronchodilators and steroids. Cough worsens with minimal activity. Viral infections are the major trigger and recovery is prolonged. FEV1 has always been normal without bronchodilator responsiveness. Chest CT when he is not actively infected is normal.

Neurologic - Partial complex and Jacksonian seizures with visual disturbances and additional minor motor components. At the onset, seizures were totally disabling with dozens of seizures per day. Uncontrolled seizures required intubation and drug induced paralysis on several occasions. During that time, he developed alexia that has resolved after about one year of intensive retraining in reading and writing. The patient's mother observed that his seizure frequency and severity improved after IGIV infusions. Neurologic problems have responded to high dose IGIV, pulse steroids and mycophenolate but not to infliximab or etanercept. Studies for autoantibodies associated with neurologic disease have been negative. Repeated MRI's have been completely normal.

Peripheral edema - At age 14 he developed dependent peripheral edema that is partially responsive to diuretics. There is neither abdominal nor pelvic compression nor vascular disease on Doppler exam. His cardiologist and endocrinologist believe that the problem is neither cardiac nor endocrine. An evaluation for dysautonomia was negative.

GI - Motility studies showed esophageal dysmotility, gastroparesis and atony of the descending colon. Diet is limited because of food allergy and multiple non-IgE mediated food intolerances and is supplemented with elemental formula. About 60% of calories are via TPN. Cholecystectomy at age 15, polyposis of the gall bladder.

Renal - Hypertension and electrolyte wasting of unknown etiology.

Endocrine - He was thought to have steroid induced adrenal suppression but a stimulation test performed after several years without prolonged steroid therapy showed no cortisol production. He is maintained with physiologic steroid replacement.

Family history - he is an only child. Mother has SLE.

Thank you,

Richard

--
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

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

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