Pulmonary capillary hemangiomatosis

{{Infobox medical condition (new)

| name =

| synonyms = Wagenvoort syndrome

| image = Pulmonary capillary hemangiomatosis (4348914308).jpg

| image_size =

| alt =

| caption = Alveolar capillary proliferation as well as proliferation of larger blood vessels, probably venules.

| pronounce =

| field = Pulmonology

| symptoms =

| complications =

| onset =

| duration =

| types =

| causes =

| risks =

| diagnosis =

| differential =

| prevention =

| treatment =

| medication =

| prognosis =

| frequency =

| deaths =

}}

Pulmonary capillary hemangiomatosis (PCH) is a disease affecting the blood vessels of the lungs, where abnormal capillary proliferation and venous fibrous intimal thickening result in progressive increase in vascular resistance.{{cite journal | last1=Ortiz-Bautista | first1=Carlos | last2=Hernández-González | first2=Ignacio | last3=Escribano-Subías | first3=Pilar | title=Enfermedad venooclusiva pulmonar y hemangiomatosis capilar pulmonar | journal=Medicina Clínica | publisher=Elsevier BV | volume=148 | issue=6 | year=2017 | issn=0025-7753 | doi=10.1016/j.medcli.2016.11.031 | pages=265–270 | pmid=28118962 | language=es}} It is a rare cause of pulmonary hypertension, and occurs predominantly in young adults.{{cite journal|vauthors=Masur Y, Remberger K, Hoefer M | title=Pulmonary capillary hemangiomatosis as a rare cause of pulmonary hypertension. | journal=Pathol Res Pract | year= 1996 | volume= 192 | issue= 3 | pages= 290–5; discussion 296–9 | pmid=8739476 | doi= 10.1016/S0344-0338(96)80232-9}}{{cite journal|vauthors=El-Gabaly M, Farver CF, Budev MA, Mohammed TL | title=Pulmonary capillary hemangiomatosis imaging findings and literature update. | journal=J Comput Assist Tomogr | year= 2007 | volume= 31 | issue= 4 | pages= 608–10 | pmid=17882042 | doi=10.1097/01.rct.0000284393.76073.87 | s2cid=35199069 }} Together with pulmonary veno-occlusive disease, PCH comprises WHO Group I' causes for pulmonary hypertension. Indeed, there is some evidence to suggest that PCH and pulmonary veno-occlusive disease are different forms of a similar disease process.{{Cite journal|last1=Lantu??joul|first1=Sylvie|last2=Sheppard|first2=Mary N.|last3=Corrin|first3=Bryan|last4=Burke|first4=Margaret M.|last5=Nicholson|first5=Andrew G.|title=Pulmonary Veno-occlusive Disease and Pulmonary Capillary Hemangiomatosis|journal=The American Journal of Surgical Pathology|volume=30|issue=7|pages=850–857|doi=10.1097/01.pas.0000209834.69972.e5|pmid=16819327 |year=2006|s2cid=25595167}}

Signs and symptoms

Nonspecific symptoms like fatigue, coughing, chest pain, and shortness of breath are what define clinical features.{{cite journal | last1=Guzman | first1=Samuel | last2=Khan | first2=Mohammad S. | last3=Chodakiewitz | first3=Yosef | last4=Khan | first4=Maham | last5=Chodakiewitz | first5=Michael S. | last6=Julien | first6=Peter | last7=Luthringer | first7=Daniel J. | title=Pulmonary capillary hemangiomatosis: a lesson learned | journal=Autopsy and Case Reports | publisher=Editora Cubo | volume=9 | issue=3 | year=2019 | pages=e2019111 | issn=2236-1960 | doi=10.4322/acr.2019.111 | pmid=31528628 | pmc=6709648 }}

Causes

At least some cases appear to be due to mutations in the eukaryotic translation initiation factor 2-alpha kinase 4 (EIF2AK4) gene.{{cite journal | last1=Best | first1=D. Hunter | last2=Sumner | first2=Kelli L. | last3=Smith | first3=Benjamin P. | last4=Damjanovich-Colmenares | first4=Kristy | last5=Nakayama | first5=Ikue | last6=Brown | first6=Lynette M. | last7=Ha | first7=Youna | last8=Paul | first8=Eleri | last9=Morris | first9=Ashley | last10=Jama | first10=Mohamed A. | last11=Dodson | first11=Mark W. | last12=Bayrak-Toydemir | first12=Pinar | last13=Elliott | first13=C. Gregory | title=EIF2AK4 Mutations in Patients Diagnosed With Pulmonary Arterial Hypertension | journal=Chest | publisher=Elsevier BV | volume=151 | issue=4 | year=2017 | issn=0012-3692 | doi=10.1016/j.chest.2016.11.014 | pages=821–828| pmid=27884767 | s2cid=3661564 }}

This condition has been reported in patients with Ehlers Danlos syndrome,{{cite journal | last1=Park | first1=Min A. | last2=Shin | first2=So Youn | last3=Kim | first3=Young Jin | last4=Park | first4=Myung Jae | last5=Lee | first5=Seung Hyeun | title=Vascular Ehlers–Danlos syndrome with cryptorchidism, recurrent pneumothorax, and pulmonary capillary hemangiomatosis-like foci | journal=Medicine | publisher=Ovid Technologies (Wolters Kluwer Health) | volume=96 | issue=47 | year=2017 | issn=0025-7974 | doi=10.1097/md.0000000000008853 | page=e8853| pmid=29381997 | pmc=5708996 }} and scimitar syndrome.{{cite journal | last1=Güttinger | first1=Eva | last2=Vrugt | first2=Bart | last3=Speich | first3=Rudolf | last4=Ulrich | first4=Silvia | last5=Schwitz | first5=Fabienne | last6=Arrigo | first6=Mattia | last7=Huber | first7=Lars C. | title=Reactive Pulmonary Capillary Hemangiomatosis and Pulmonary Veno-Occlusive Disease in a Patient with Repaired Scimitar Syndrome | journal=Case Reports in Cardiology | publisher=Hindawi Limited | volume=2016 | year=2016 | issn=2090-6404 | doi=10.1155/2016/9384126 | doi-access=free | pages=1–5| pmid=27069695 }}

Diagnosis

Pulmonary artery hypertension, which manifests as enlarged pulmonary arteries, is a common imaging characteristic of pulmonary capillary hemangiomatosis. Additionally, as pulmonary artery hypertension worsens, typical CT imaging findings of right ventricular hypertrophy, leftward interventricular septum bowing, right atrial enlargement, and reflux of IV contrast into the inferior vena cava and hepatic veins can indicate secondary right heart dysfunction.

Treatment

The only definitive treatment for this condition currently is lung transplantation.

Imatinib may be of use.{{cite journal | last1=Ogawa | first1=Aiko | last2=Miyaji | first2=Katsumasa | last3=Matsubara | first3=Hiromi | title=Efficacy and safety of long-term imatinib therapy for patients with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis | journal=Respiratory Medicine | publisher=Elsevier BV | volume=131 | year=2017 | issn=0954-6111 | doi=10.1016/j.rmed.2017.08.032 | pages=215–219| pmid=28947033 | doi-access=free }}

Epoprostenol does not appear to be of use.{{cite journal | last1=S | first1=Akagi | last2=K | first2=Nakamura | last3=H | first3=Matsubara | last4=A | first4=Ogawa | last5=T | first5=Sarashina | last6=K | first6=Ejiri | last7=H | first7=Ito | title=Epoprostenol Therapy for Pulmonary Arterial Hypertension | journal=Acta Medica Okayama | publisher=Acta Med Okayama | volume=69 | issue=3 | date=2015 | pages=129–136 | issn=0386-300X | pmid=26101188 | doi=10.18926/AMO/53519 | s2cid=25069450 |url=https://pubmed.ncbi.nlm.nih.gov/26101188/ | access-date=January 28, 2024 }}

Epidemiology

The prevalence of this disease is estimated to be < 1/million.{{cite journal | last1=Szturmowicz | first1=Monika | last2=Kacprzak | first2=Aneta | last3=Szołkowska | first3=Małgorzata | last4=Burakowska | first4=Barbara | last5=Szczepulska | first5=Ewa | last6=Kuś | first6=Jan | title=Pulmonary Veno-Occlusive Disease: Pathogenesis, Risk Factors, Clinical Features and Diagnostic Algorithm—State of the Art | journal=Advances in Respiratory Medicine | publisher=MDPI AG | volume=86 | issue=3 | date=June 30, 2018 | issn=2543-6031 | doi=10.5603/arm.2018.0021 | pages=131–141| pmid=29960280 | doi-access=free }} The usual age at presentation is between 20 and 40 but it has been reported in the newborn.{{cite journal | title=Hemangiomatosis capilar pulmonar congénita en un recién nacido | journal=Archivos Argentinos de Pediatria | publisher=Sociedad Argentina de Pediatria | volume=115 | issue=1 | date=February 1, 2017 | issn=0325-0075 | doi=10.5546/aap.2017.e17 | pmid=28097848 | last1=Sposito Cavallo | first1=S. L. | last2=MacIas Sobrino | first2=L. A. | last3=Marenco Altamar | first3=L. J. | last4=Mejía Alquichire | first4=A. F. | pages=e17–e20 | doi-access=free }}

History

This condition was first described in 1978.{{cite journal | last1=WAGENVOORT | first1=C. A. | last2=BEETSTRA | first2=A. | last3=SPIJKER | first3=J. | title=Capillary haemangiomatosis of the lungs | journal=Histopathology | publisher=Wiley | volume=2 | issue=6 | year=1978 | issn=0309-0167 | doi=10.1111/j.1365-2559.1978.tb01734.x | pages=401–406| pmid=730121 | s2cid=1187730 }}

Outcome

Median survival without treatment is 3 years.{{cite journal | last1=Ma | first1=Lijiang | last2=Bao | first2=Ruijun | title=Pulmonary capillary hemangiomatosis: a focus on the EIF2AK4 mutation in onset and pathogenesis | journal=The Application of Clinical Genetics | publisher=Informa UK Limited | year=2015 | volume=8 | pages=181–188 | issn=1178-704X | doi=10.2147/tacg.s68635 | doi-access=free | pmid=26300654 | pmc=4536836 }}

Animals

This condition has been reported in cats.{{cite journal | last1=Jenkins | first1=Tiffany L. | last2=Jennings | first2=Ryan N. | title=Pulmonary capillary hemangiomatosis and hypertrophic cardiomyopathy in a Persian cat | journal=Journal of Veterinary Diagnostic Investigation | publisher=SAGE Publications | volume=29 | issue=6 | date=July 28, 2017 | issn=1040-6387 | doi=10.1177/1040638717723686 | pages=900–903| pmid=28754081 }} and dogs.{{cite journal | last1=Reinero | first1=Carol R. | last2=Jutkowitz | first2=L. Ari | last3=Nelson | first3=Nathan | last4=Masseau | first4=Isabelle | last5=Jennings | first5=Samuel | last6=Williams | first6=Kurt | title=Clinical features of canine pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis | journal=Journal of Veterinary Internal Medicine | publisher=Wiley | volume=33 | issue=1 | date=November 29, 2018 | issn=0891-6640 | doi=10.1111/jvim.15351 | pages=114–123| pmid=30499214 | pmc=6335444 }}