[CIS PIDD] [cis-pidd] Challenging case of intestinal lymphangiectasia: a few questions in search of answers

[CIS-PIDD]

I have been providing care to a very nice 57-year-old manwith intestinal lymphangiectasia since 2004. He has had many challenging issuesalong this path and I would appreciate the input of experts in this group tohelp me with continuing his care. I will summarize the issues for which I am stillseeking sensible answers, and will pose my questions first prior to presentingthe case to provide a focus before you read through a rather lengthy history:1.     Is there any roll for immunoglobulin replacementin patients with intestinal lymphangiectasia? Is there any reason to suppose HyQvia might provide any advantage over traditional IgSC without hyaluronidase in this group of patients?2.     What is the risk of opportunistic infections insuch patients and the role of antimicrobial prophylaxis?3.     Are there any experimental approaches withmedications that are available for the treatment of other conditions that couldbe applied to patients with this condition? For instance targeting thelymphatic vessels in the GI tract with sirolimus (rapamycin) that has showneffectiveness in lymphangiomyomatosis or vedolizumab (Entyvio) that suppresses theinflammation in IBD. By preventing blood lymphocytes from entering the gut, itmay minimize the loss of lymphocytes into the gut lumen in intestinal lymphangiectasia.The absence of any published data, and his altered pharmacokinetics resultingfrom malabsorption or accelerated elimination through his GI tract as well as theconcern that these compounds may further suppress his already weak residentialimmune function have precluded me from considering an empiric therapeutic trial.4.     Is there anybody in the US that has specificexpertise in intestinal lymphangiectasia, who could provide a second opinionand some guidance to me? I know that many years ago a cohort of patients werefollowed by Waldman and Strober at the NIH, but I am not aware that anybody hastaken over that protocol.
He has had chronic diarrhea and frequent infections sincehis infancy or early childhood. When I first met him he was labeled with adiagnosis of CVID.  However beyond hypogammaglobulinemia,he also had lymphocytopenia, protein losing enteropathy, cutaneous flat wartsaffecting his upper extremities from his injuries to his upper arms, which aredefining features of intestinal lymphangiectasia. This diagnosis was confirmedby the capsule video endoscopy and subsequent biopsy. He has also had asthma andallergy to cats and grass since his youth with superimposed bronchiectasis inboth lower lobes measuring up to 6 mm diameter on his most recent chest CT scanthis month. This has been complicated by pseudomonas colonization and chronicbronchitis which to some extent resemble the picture in cystic fibrosis anddiffuse panbronchiolitis. Other comorbidities include a history of pulmonaryaspergillosis, severe GERD, eustachian tube dysfunction with serous otitis mediarequiring repeated tympanostomy tube placement or myringotomy, chronicsinusitis that has not recurred since he underwent FESS in 2009 and history ofatrial fibrillation maintained in SR with flecainide and digoxin, as well as situationaldepression and anxiety. 
He has had chronic cough with sputum production at baselineand recurrent respiratory exacerbations that have been responsive toantibiotics along with oral prednisone. He just came down with yet anotherepisode and is currently treated empirically with Cipro 500 bid and Tobi (nebulizedtobramycin) bid and prednisone. On 2 different occasions IgSC was attempted withVivaglobin and subsequently Hizentra , but he was unable to tolerate thetreatment due to substantial side effects that he described as having a bad flu. He felt sick all the time on Vivaglobin thathe started in April 2009 and took initially 13 ml every other day. It broughthis IgG up, but caused generalized malaise. He reported that upon arising inthe morning, a wave of diffuse pain and fatigue would overtake his body. He wasstarted on octreotide for his protein losing enteropathy in Sept. 2009, whichhelped substantially with his GI symptoms, and brought up his serum albumin andtotal protein but augmented the symptoms that were caused by immunoglobulinreplacement, especially nausea that could not be controlled even with Zofranand Reglan. The loss of appetite led to anorexia and weight loss even though hewas forcing himself to eat and taking nutritional supplements. His dose couldbe reduced because octreotide also resulted in an increase in his IgG level thatpeaked at 705. He sequentially went down with Vivaglobin to 10 mL, and then 6 mLevery other day. Finally, he took only 3 mL daily, which only worsened his sideeffects that became constant, whereas on every other day dosing he felt somerelief between the doses before IgG was administered and until it was taken up intohis circulation. Finally, in December 2009 Vivaglobin was stopped. He has beentaking antibiotic prophylaxis with Bactrim. For a while on Tobi and Pulmozyme alongwith the Vest airway clearance for chronic pseudomonas bronchitis and Vfend forpulmonary aspergillosis that could be discontinued. Without any immunoglobulinsupplementation he was able to mount a good response to Prevnar with protectivetiters to nine of 13 serotypes that were included in the vaccine in May 2013, buta year later his titers were below the level detection to almost all serotypes.Treatment with macrolides was attempted based on their effectiveness against diffusepanbronchiolitis, but he had substantial difficulty tolerating it due to worseningof his underlying chronic diarrhea. Finally, the dose azithromycin could beraised gradually to 250 mg daily with the help of codeine to suppress his GImotility and his respiratory symptoms drastically improved. Unfortunately thiswas the only transient and he started to have breakthrough respiratoryexacerbations again despite taking Bactrim and azithromycin daily. In Februaryof the last year he was started on Hizentra 40 mL (8g) weekly and the same symptomsthat he had experienced with Vivaglobin returned, but this time more severely. Headache,stomach pain, diarrhea, increased cough, and malaise became his daily routine. Anotheressential problem with Hizentra that he had not experienced with Vivaglobin wasa decrease in his cognitive ability and confusion which he felt stripped him ofwho he was and rendered him unable to work effectively. Switching to adifferent product such as Gamunex was suggested, but he feels that life is notworth living, when IgSC makes him feel so miserable and he would prefer living with and dying from his disease than the treatment with IgSC.
In will brief here is a summary of his most recent laboratoryfindings: CBC w/ diff: WBC 11.2, Hb 50.5, plt 348; N 76% (ANC 8.5), L 10% (ALC 1.1), M 11% (AMC 1.3) FACS lymphocyte analysis: ALC 1055 CD3 726 CD4 84 CD8 634 CD19 100 CD16/CD56 209
Immunoglobulins: IgG 476, IgA 163, IgM 24Essentially these have been in the same range since 12/2015.Total protein is 5.9 and albumin 3.2 with the rest of CMP in normal range. ESR wasonly 3.
Please let me know, if there is any further detail that Icould furnish, which might shed some light on his clinical picture. I would verymuch appreciate any suggestion and advice that this group can provide.
Best regards,


 
Soheil Chegini, M.D.

Exton Allergy & Asthma Associates

656 West Lincoln Hwy.

Exton, PA 19341

Phone: (610) 269-3066

Fax: (610) 269-8615

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