Rare Lung Disease II

LGD Webinar Q&A

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Lung Involvement in Lymphangiomatosis & Gorham’s Disease (Webinar held Thurs, Aug 9, 2012)

Listed below are post-webinar questions answered by presenters, Dr. Debra Boyer of Children’s Hospital Boston and Dr. Denise Adams of Cincinnati Children’s Hospital. The questions and answers provided below are specific to the webinar that was presented and is intended for educational purposes only. You should not rely on this information as a substitute for a diagnosis from your physician.

  1. Is the role of the thoracic duct of paramount importance to patients with chylothorax?
  2. Do you think there is a connection between spleen, bone, bone marrow (spindle cells and thrombocytopenia) and thoracic duct as targeted organs by aggressive lymphatic disorders
  3. How do you treat bilateral chylothorax not responding to conservative treatments? 
  4. How frequently do you see abnormal inflammatory markers in patients?
  5. Is there any evidence that the use of sirolimus improve the parenchymal lung damage?
  6. What might the impact be of the sirolimus study out of Univ. of Chicago re: taking with grapefruit juice increases absorption?
  7. How can I talk more to a specialist and get more involved in research?
  8. Will the medical board require physicians to check for this disease (LGD) as a standard practice when patients arrive with asthma and pneumonia like symptoms?
  9. Regarding thoracic duct ligation, which symptoms indicate choosing this procedure? What outcomes were achieved?
  10. To whom can we refer these patients - oncology, interventional radiology or surgery?
  11. Is anyone developing a mechanism to facilitate more collaboration between patients, clinicians and scientists to make clinical materials available for DNA analysis?
  12. There is some literature using propranolol and sildenafil in lymphatic malformations, do you have some experience with these drugs?
  13. Would you recommend Sirolimus in patients with asymptomatic generalized lymphangiomatosis, multiple bone lesion (12) and spleen lesion?
  14. Do you think Sirolimus would be beneficial for those with GSD?    
  15. Is it normal to see platelet counts under five and clotting factors extremely low when there is little bone involvement?
  16. Regarding Gorham’s disease and the traditional treatment, bisphosphonate and interferon. Is there a maximum number for bisphosphonate treatments?
  17. Do you have more information about the relative frequency of the different types of malformation and tumor that you mentioned in the presentation?

Ques. #1:  Is the role of the thoracic duct of paramount importance to patients with chylothorax? (Juan Carlos, Madrid)

  • Role of the thoracic duct may be of paramount importance to some patients with chylothorax but it is probably a more global abnormality of the pulmonary lymphatic network in other patients.   Better use and techniques of imaging (lymphangiograms) may help with this in the future.  Some case reports in which the thoracic duct is ligated has not improved the effusions.  Sirolimus appears to be especially beneficial in patients that have effusions. (Pediatr Blood and Cancer 2011;57:1018-1024.) Effusions in the past have been very significant to patients.  In our retrospective analysis, fluid complications were identified as high risk (p<0.001).  Forty percent of cases with fluid issues have mortality from the effusion.  Again this was retrospective data.

Ques. # 2: Do you think there is a connection between spleen, bone, bone marrow (spindle cells and thrombocytopenia) and thoracic duct as targeted organs by aggressive lymphatic disorders? (Juan Carlos, Madrid)

  • I think there is definite connection between these organs.  There would have to be, as clinically, patients with Gorham’s Syndrome, generalized lymphatic anomaly and kaposiform lymphangiomatosis can have disease in all of these areas.  We know that in the human and in the animal model there are many connections and interactions among these organs.   Lymphatic vessels, lymph nodes, the spleen and the myeloid tissue in the bone marrow all develop from the lateroplate of the mesoderm.  Spindle cells need to be further classified as their origin appears to be the endothelial cell, but is this initiating cell or is this caused by a disease process?   Thrombocytopenia is related to entrapment of platelets in the lymphatic component of these disorders but also in the spleen if it is enlarged.

Ques. # 3: How do you treat bilateral chylothorax not responding to conservative treatments?

  • Bilateral chylothrorax requires a multidisciplinary approach by specialists and varies with each patient.  Diet, ocreotide, radiologic intervention and surgical intervention have all been used. Also new agents such as rapamycin have been used.

Ques. # 4: How frequently do you see abnormal inflammatory markers in patients?

  • Inflammatory markers have not been consistently checked on all patients and can differ. Several centers are presently analyzing inflammatory markers.   Some are analyzing fluid for inflammatory cytokines. 

Ques. #5: Is there any evidence that the use of sirolimus improve the parenchymal lung damage?

  • First of all it is important to determine the etiology of the parenchymal lung disease.  Unfortunately some of the parenchymal lung disease is a chronic process that cannot be completely resolved by any medical therapy that we have available now.    

Ques. # 6: What might be the impact of the sirolimus study out of Univ. of Chicago finding taking with grapefruit juice increases absorption — increasing the levels by >350%?  (Lisa, LA)

  • It is well known that there are many drugs, naturopathic remedies, foods and other states that interfere with the metabolism of rapamycin (sirolimus).  In our study at Cincinnati, there are medications that we do not use concominently and we do not allow grapefruit juice or the fruit during the study because of this.  

Ques. # 7: How can I talk more to a specialist and get more involved in research? 

Ques. # 8: My son passed away three years ago from diffused pulmonary lymphangiomatosis and we did not know he had the disease until one hour prior to his passing. My son was misdiagnosed for many years. Will the medical board check for this disease as a standard practice when patients arrive with asthma and pneumonia like symptoms? (Dave, MA)

  • We are sorry for this and because this is such a rare disease we are trying to increase awareness through education of medical students, residents and other trainees.  We are also trying to speak more at international meetings.   We further are improving awareness at the National Institutes of Health (NIH).  This will hopefully enable more physicians to be trained in these diagnoses in the future. 

Ques. #9: Regarding thoracic duct ligation, which symptoms indicate choosing this procedure? What outcomes were achieved? (Myrna, NY) 

  • Again these procedures require a team of physicians to review the case and determine the best treatment.  There are unfortunately no series with great numbers that analyzes outcome measurements for patients with thoracic duct ligation.

Ques. # 10: To whom can we refer these patients - oncology, interventional radiology or surgery?

  • The best place to refer patients is to a multidisciplinary vascular anomaly center.  The LGDA and other support groups can help with this. 

Ques. # 11: Advances in DNA sequencing have made it possible to identify the underlying cause for vascular malformations. Patients, clinicians and scientists need to work together to make precious clinical material available for DNA analysis. Is anyone developing a mechanism to facilitate? (Matthew, MA)

  • This collaboration is much needed and very important.  LGDA and other support groups are planning registries and tissue repositories.

Ques. #12: There is some literature using propranolol and sildenafil in lymphatic malformations, do you have some experience with these drugs? (Zavala, Chile) 

  • Propranolol was reported in one patient with a generalized lymphatic anomaly who was also on many other medications.    We have had several of our patients on this medication but the results are mixed.  Further studies need to be done to evaluate efficacy.  Sildenafil is being used for lymphatic malformations , mostly soft tissue, there have been some impressive results though time to response can be 4 – 6 months and it is unclear is effect on effusions or bony disease.   Please go to www.clinicaltrials.gov  for all studies.

Ques. # 13: Would you recommend Sirolimus in patients with asymptomatic generalized lymphangiomatosis, multiple bone lesion (12) and spleen lesion? (Iris, Chile)

  • This is an interesting question.  Our present study is for complicated lesions and bony lesions, spleen, and or effusions are included as complicated.   There is some question as to better response in patients treated at a younger age. 

Ques. #14: Do you think Sirolimus would be beneficial for those with GSD?    (Michelle, FL)   

  • GSD patients are included in our study and we have had some results but it is early and we need to complete the study in order to assess this.   

Ques. #15: Is it normal to see platelet counts under five and clotting factors extremely low when there is little bone involvement? My son had bleeding and bruising problems so serious that we had to remove his spleen yesterday because it became too dangerous to wait for medications to have an impact. (Jenny)

  • These coagulopathies are seen in several different vascular anomalies.  It is very important that the proper diagnosis is made so that the right treatment is given.  If a spleen is very large it can trap platelets.   Lesions that cause coagulopathies are venous malformations, venous lymphatic malformations, kaposiform hemangioendothelioma, kaposiform lymphangiomatosis and capillary lymphatic venous malformations.  Other tumors can cause these issues as well. 

Ques. # 16: Regarding Gorham’s disease and the traditional treatment, bisphosphonate and interferon. Is there a maximum number for bisphosphonate treatments?

  • For Gorham’s disease treatment needs to be used for a long period of time to see results.   The ideal time has not been studied but response has been seen at six months, at one year and at two years.   (Robert, FL)

Ques. # 17: I would be interested to know more about the relative frequency of the different types of malformation and tumor that you mentioned in the presentation 

  • There is no clear epidemiologic data on this. We can extrapolate from the patients that we have in our clinical registries. (Joe)

For further information please contact:

Courtney L. White
Director, Patient Outreach
American Thoracic Society
25 Broadway, 8th Fl.
New York, NY 10004
(212) 315-8600
cwhite@thoracic.org

Jack Kelly
President
Lymphangiomatosis & Gorham's
Disease Alliance (LGDA)
19919 Villa Lante Place
Boca Raton, FL   33434
561-441-9766
www.LGDAlliance.org