Six-year Follow-up of a Patient with Multiple Angiomatosis Involving Skeleton, Thoracic and Abdominal Cavities and the Gut Wall

Česká verzia

Authors: Z. Adam ¹; M. Matýšková ¹; M. Tomíška ¹; Z. Řehák ²; R. Koukalová ²; L. Křikavová ³; L. Pour ¹; M. Krejčí ¹; P. Szturz ¹; L. Zahradová ¹; M. Mechl ³; M. Moulis ⁴; J. Vaníček ⁵; Č. Neuman ⁶; M. Navrátil ¹; K. Veselý ⁷; R. Hájek ¹; J. Mayer ¹
Authors place of work: Interní hematoonkologická klinika, LF MU a FN Brno ¹; PET CT oddělení, Masarykův onkologický ústav, Brno ²; Radiologická klinika, LF MU a FN Brno ³; Ústav patologické anatomie, LF MU a FN Brno ⁴; Klinika zobrazovacích metod, LF MU a FN u sv. Anny Brno ⁵; Chirurgická klinika, LF MU a FN Brno ⁶; I. patologicko-anatomický ústav, LF MU a FN u sv. Anny Brno ⁷
Published in the journal: Klin Onkol 2012; 25(1): 47-62
Category: Kazuistiky

Summary

Backgrounds:
Multiple angiomatosis is a rare disease causing angiomatous lesions in multiple organs and tissues with a risk of life-threatening haemorrhage.

Observation:
A young man was diagnosed with multiple angiomatosis at the age of 28 after two years of back and abdominal pain. Laparotomy revealed multiple spongy lesions mostly within the retroperitoneal space. Also, an involvement of the gut wall, bones and mediastinum was evident. After 6 years of treatment, the disease has been stabilized. Bone pain ceased with a significant contribution of zoledronate. Using CT and MR imaging, the effectiveness of antiangiogenic drugs was evaluated. Furthermore, treatment response was evaluated using laboratory values for coagulation and blood count, as angiomatous proliferation is known to be associated with disseminated intravascular coagulation and anaemia.

Results:
Baseline laboratory examination revealed elevated D-dimer (more than 20 µg/mL), low fibrinogen (1.4 g/L), and the presence of fibrin monomers. After treatment with 6 mil. IU of interferon-alpha thrice weekly, there was only partial improvement in D-dimer (17.2 µg/mL) and fibrinogen (1.5 g/L) concentrations but fibrin monomers remained positive. After thalidomide (100 mg daily), D-dimer decreased to 6.1 µg/mL and fibrinogen levels increased to 1.9 g/L with the disappearance of fibrin monomers. CT scanning showed significant regression of angiomatous lesions. Progressive neuropathy was the reason to lower the dose of thalidomide by half and this caused D-dimer to rise again. Switching to lenalidomide 10 mg daily led to an increase in D-dimer to 10.8 µg/mL and decrease in haemoglobin concentration to 124 g/L. Fibrin monomers became positive again. Combined therapy with thalidomide (50 mg/day) and lenalidomide (10 mg days 1–21 in 28-day cycles) has led to stabilisation of the disease. Median concentration of haemoglobin increased to 131 (84–141) g/l. The median of D-dimer decreased to 9.3 (8.0–17) µg/mL.

Conclusion:
Thalidomide in the dose of 100 mg daily led to better stabilisation of the disease than interferon-alpha. However, lowering the dose because of adverse effects failed to be effective sufficiently. Lenalidomide 10 mg daily was well-tolerated but insufficient to improve D-dimer and haemoglobin concentrations. Therefore, for further treatment we have decided to use the combination of lenalidomide and thalidomide in doses of 10 mg and 50 mg, respectively because both drugs have desirable antiangiogenic activities with different adverse effect profiles. On this therapy, the patient’s disease has been stable for 9 months.

Key words:
angiomatosis – zoledronate – thalidomide – interferon alpha – lenalidomide – disseminated intravascular coagulation

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Submitted:
29. 11. 2011

Accepted:
3. 7. 2011

Zdroje

1. Haggstrom AN, Drolet BA, Baselga E et al. Hemangioma Investigators Group. Prospective study of infantile hemangiomas: demographic, prenatal and perinatal characteristics. J Pediatr 2007; 150(3): 291–294.

2. Kalousová J. Komplexní léčba hemangiomatózy jater. Čes Slov Pediat 1994; 49(11): 698–699.

3. Bláhová K, Mottl M, Tůma S. Hemangiomatóza jater u tříměsíčního kojence. Čes Slov Pediat 1991; 46: 434–436.

4. Mottl H, Koutecký J, Buncová M et al. Sdružený výskyt preaurikulárního hemangiomu s hemangiomatózou tenkého střeva a mesenteria. Čes Slov Pediat 1985; 40: 523–526.

5. Mottl H. Teleangiektatický hemangiom: Difúzní hemangiomatóza mesenteria a střeva. Čes Slov Pediat 1985; 40: 523–526.

6. Srbová J. Hemangiomatóza. Sestra 2005; 15(1): 46.

7. Langner C, Thonhofer R, Hagenbarth K et al. Diffuse Hämangiomatose von Leber und Milz bei Erwachsenen. Pathologe 2001; 22(6): 424–428.

8. Ito K, Ichiki T, Ohi K et al. Pulmonary capillary hemangiomatosis with severe pulmonary hypertension. Circ J 2003; 67(9): 793–795.

9. Kawasaki K, Ito T, Tsuchiya T et al. Is angiomatosis an intrinsic pathohistological features of massive osteolysis? Report of an autopsy case and review of the literature. Virchows Arch 2003; 442(4): 400–406.

10. Dufau JP, Tourneau A, Audouin J et al. Isolated diffuse hemangiomatosis of the spleen with Kasabach-Merrit-like syndrome. Histopathology 1999; 35(4): 337–344.

11. Kairi-Vassilatou E, Grapsa D, Kontogianni-Katsarou K et al. Clinicopathological features of unusual vascular leasions of the pelvis, retroperitoneum and colon in females: a report of five cases and review of the literature. Eur J Gynaecol Oncol 2006; 27(3): 250–255.

12. Bölke E, Gripp S, Peiper M et al. Multifocal epithelia hemangioendotelioma: a case report of a clinical chemeleon. Eur J Med Res 2006; 11: 1–15.

13. Marinis, A, Kairi E, Theodosopoulos T et al. Right colon and liver hemangiomatosis: a case report and review of literature. World J Gastroenterol 2006; 12(39): 6405–6407.

14. Moon WS, Yy HC, Lee JM et al. Diffuse hepatic hemangiomatosis in an adult. J Korean Med Sci 2000; 15(4): 471–474.

15. Blatný J, Štěrba J, Magnová O. Léčba život ohrožujícího krvácení u kojence s hemangiomatózou a s projevy Kasabacha-Merritové pomocí rekombinantního faktoru VIIA. Čes Slov Pediat 2002; 57(7): 401–402.

16. Werner JA, Eivazi B, Folz BJ et al. State of the Art zur Klassifikation, Diagnostik und Terapie von zervikofazialen Hämangiomen und vaskulären Malformationen. Laryngorhinootologie 2006; 85(12): 883–891.

17. Neuman J, Rosioreanu A, Schuss A et al. Radiology-pathology conference: sclerosing hemangioma of the lung. Clin Imaging 2006; 30(6): 409–412.

18. Levy AD, Abbott RM, Rohrmann CA Jr et al. Gastrointestinal hemangiomas: imaging findings pathologic correlation in pediatric and adult patients. AJR Am J Roentgenol 2001; 177(5): 1073–1081.

19. Scafidi DE, McLeary MS, Young LW. Diffuse neonatal gastrointestinal hemangiomatosis: CT finding. Pediatr Radiol 1998; 28(7): 512–514.

20. Hsu RM, Horton KM, Fishman EK. Diffuse cavernous hemangiomatosis of the colon: findings on three-dimensional CT colonography. AJR Am J Roentgenol 2002; 179(4): 1042–1044.

21. Djouhri A, Arrivé L, Bouras T et al. Diffuse cavernous hemangioma of the rectosigmoid colon: imaging findings. J Comput Assist Tomogr 1998; 22(6): 851–855.

22. Lyon DG, Mantia AG. Large-bowel hemangiomas. Dis Colon Rectum 1984; 27(6): 404–414.

23. Weiss SW, Goldblum JR. Enzinger and Weiss’s Soft Tissue Tumors. 4th ed. Philadelphia, PA: Mosby 2001: 891–914.

24. Bank ER, Hernandez RJ, Byrne WJ. Gastrointestinal hemangiomatosis in children: demonstration with CT. Radiology 1987; 165(3): 657–658.

25. Park DD, Ricketts RR. Infantile gastrointestinal hemangioma as a couse of chronic anemia. South Med J 1992; 85(2): 201–203.

26. Caseiro-Alves F, Brito J, Araujo AE et al. Liver haemangioma: common and uncommon findings and how to improve the differential diagnosis. Eur Radiol 2007; 17(6): 1544–1554.

27. Goodman P, Dominquez R, Castillo M. Diffuse neonatal hemagniomatosis: imaging finding in two patients. Comput Med Imaging Graph 1992; 16(2): 117–120.

28. Lin CH, Hsieh HF, Yy JC et al. Spontaneous rupture of a large exogastric hemangioma complicated by hemoperitoneum and sepsis. J Formos Med Assoc 2006; 105(12): 1027–1030.

29. Mulliken JB, Boon LM, Takahashi et al. Pharmacologic therapy for endangering hemangiomas. Curr Opin Dermatol 1995; 2: 109–113.

30. Hasan Q, Tan ST, Gush J et al. Steroid therapy of a proliferating hemangioma: histochemical and molecular changes. Pediatrics 2000; 105(1 Pt 1): 117–120.

31. Uysal KM, Olgun N, Erbay A et al. High-dose oral methylprednisolone therapy in childhood hemangiomas. Pediatr Hematol Oncol 2001; 18(5): 335–341.

32. Hurvitz SA, Hurvitz CH, Sloninsky L et al. Successful treatment with cyclophosphamide of life-threatening diffuse hemangiomatosis involving the liver. J Pediatr Hematol Oncol 2000; 22(6): 527–532.

33. Gottschling S, Schneider G, Meyer S et al. Two infants with life-threatening diffuse neonatal hemangiomatosis treated with cyclophosphamide. Pediatr Blood Cancer 2006; 46(2): 239–242.

34. White CW. Treatment of hemangiomatosis with recombinant interferon alpha. Semin Hematol 1990; 27 (3 Suppl 4): 15–22.

35. Takahashi A, Ogawa C, Kanazawa T et al. Remission induced by interferon alpha in a patient with massive osteolysis and extension of lymph-hemangiomatosis: a severe case of Gorham-Stout syndrome. J Pediatr Surg 2005; 40(3): E47–E50.

36. Nevolová P, Bláhová K, Kabelka Z. Úspěchy léčby rozsáhlé hemangiomatózy u 17měsíčního dítěte po podání interferonu alfa. Ref Výběr Dermatovenereol 1996; 2: 83.

37. Harper L, Michael JL, Enjolras O et al. Successful management of a retroperitoneal kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon using alpha-interferon. Eur J Pediatr Surg 2006; 16(5): 369–372.

38. D’Amato RJ, Loughnan MS, Flynn E et al. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 1994; 91(9): 4082–4085.

39. Kenyon BM, Browne F, D’Amato RJ. Effects of thalidomide and related metabolites in a mouse corneal model of neovascularization. Exp Eye Res 1997; 64(6): 971–978.

40. Or R, Feferman R, Shoshan S. Thalidomide reduces vascular density in granulation tissue of subcutaneously implanted polyvinyl alcohol sponges in quinea pigs. Exp Hematol 1998; 26(3): 217–221.

41. Bauer KS, Dixon SC, Figg WD. Inhibition of angiogenesis by thalidomide requires metabolic activation, which is species dependent. Biochem Pharmacol 1998; 55(11): 1827–1834.

42. Rajkumar SV, Witzig TE. A review of angiogenesis and antiangiogenic therapy with thalidomide in multiple myeloma. Cancer Treat Rev 2000; 26(5): 351–362.

43. Vacca A, Scavelli C, Montefusco V et al. Thalidomide downregulates angiogenic genes in bone marrow endothelial cells of patients with active multiple myeloma. J Clin Oncol 2005; 23(23): 5334–5346.

44. Ma L, del Soldato P, Wallace JL. Divergent effects of new cyclooxygenase inhibitors on gastric ulcer healing: Shifting the angiogenic balance. Proc Natl Acad Sci USA 2002; 99(20): 13243–13247.

45. Masferrer JL, Leahy KM, Koki AT et al. Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res 2000; 60(5): 1306–1311.

46. Gilheeney SW, Scott, RM, Turner C et al. Treatment of Von Hippel Lindau associated hemangioblastoma in pediatric patients with bevacizumab (Avastin). Neurolo-Oncology 2007; 9(2): Abstract 168.

47. Nelson SC, Bostrom BC. Successful use of bevacizumab in life threatening steroid-resistant infantile hepatic hemangioendotelioma. Pediatr Blood Cancer 2007; 48: Abstract 611.

48. Ramasamy-Karthik Stehen L, Jackie C et al. Bevacizumab for POEMS syndrome. Blood 2006; 108(11 part 2): Abstract 366B.

49. Ziemssen F, Voelker M, Inhoffen W et al. Combined treatment of juxtapapillary retinal capillary haemagnioma with intravitreal bevacizumab and photodynamic therapy. Eye 2007; 21(8): 1125–1126.

50. von Buelow M, Pape S, Hoerauf H. Systemic bevacizumab treatment of a juxtapappillary retinal haemangioma. Acta Ophthalmol Scand 2007; 85(1): 114–116.

51. Meyerle CB, Freund KB, Iturralde D et al. Intravitreal bevacizumab (Avastin) for retinal angiomatous proliferation. Retina 2007; 27(4): 451–457.

52. Li EC, Davis LE. Zoledronic acid: a new parenteral bisphosphonate. Clin Ther 2003; 25(11): 2669–2708.

53. Wood JM, Bonjean K, Ruetz S et al. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 2002; 302(3): 1055–1061.

54. Hasmim M, Bieler G, Rüegg C. Zoledronate inhibits endothelial cell adhesion, migration and survival through the suppression of multiple, prenylation-dependent signaling pathways. J Thromb Haemost 2007; 5(1):166–173.

55. Bellahcène A, Chaplet M, Bonjean K et al. Zoledronate inhibits alphavbeta3 and alphavbeta5 integrin cell surface expression in endothelial cells. Endothelium 2007; 14(2): 123–130.

56. Giraudo E, Inoue M, Hanahan D. An amino-bisphosphonate targets MMP-9–expressing macrophages and angiogenesis to impair cervical carcinogenesis. J Clin Invest 2004; 114(5): 623–633.

57. Croucher PI, De Hendrik R, Perry MJ et al. Zoledronic acid treatment of 5T2MM-bearing mice inhibits the development of myeloma bone disease: evidence for decreased osteolysis, tumor burden and angiogenesis, and increased survival. J Bone Miner Res 2003; 18(3): 482–492.

58. Fournier P, Boissier S, Filleur S et al. Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Res 2002; 62(22): 6538–6544.

59. Adam Z, Ševčík P, Vorlíček J et al. Kostní nádorová choroba. Praha: Grada 2004.

60. Wood J, Bonjean K, Ruetz S et al. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 2002; 302(3): 1055–1061.

61. Loo WJ, Lanigan SW. Recent advances in laser therapy for the treatment of cutaneous vascular disorders. Lasers Med Sci 2002; 17(1): 9–12.

62. Winter H, Dräger E, Sterry W. Sclerotherapy for treatment of hemangiomas. Dermatol Surg 2000; 26(2): 105–108.

63. Geh JL, Geh VS, Jemec B et al. Surgical treatment of periocular hemangiomas: a single-center experience. Plast Reconstr Surg 2007; 119(5): 1553–1562.

64. Heidt J, Langers AM, van der Meer FJ et al. Thalidomide as treatment for digestive tract angiodysplasias. Neth J Med 2006; 64(11): 425–428.

65. Bowcock SJ, Patrick HE. Lenalidomide to control gastrointestinal bleeding in hereditary haemorrhagic telangiectasia: potential implications for angiodysplasias? Br J Haematol 2009; 146(2): 220–222.

66. Sumrall A, Fredericks R, Berthold A et al. Lenalidomide stops progression of multifocal epithelioid hemangioendothelioma including intracranial disease. J Neurooncol 2010; 97(2): 275–277.

67. Kim LH, Hogeling M, Wargon O et al. S. Propranolol: useful therapeutic agent for the treatment of ulcerated infantile hemangiomas. J Pediatr Surg 2011; 46(4): 759–763.

68. Cushing SL, Boucek RJ, Manning SC et al. Initial experience with a multidisciplinary strategy for initiation of propranolol therapy for infantile hemangiomas. Otolaryngol Head Neck Surg 2011; 144(1): 78–84.

69. Erbay A, Sarialioglu F, Malbora B et al. Propranolol for infantile hemangiomas: a preliminary report on efficacy and safety in very low birth weight infants. Turk J Pediatr 2010; 52(5): 450–456.

70. Bonanno C, Paccanaro M, Fontanellilea A. Propranolol for severe hemangioma of infancy. J Cardiovasc Med (Hagerstown) 2011; 12(1): 73.

71. Jadhav VM, Tolat SN. Dramatic response of propranolol in hemangioma: report of two cases. Indian J Dermatol Venereol Leprol 2010; 76(6): 691–964.

72. Arneja JS, Pappas PN, Shwayder TA et al. Management of complicated facial hemangiomas with beta-blocker (propranolol) therapy. Plast Reconstr Surg 2010; 126(3): 889–895.

73. Holmes WJ, Mishra A, Gorst C et al. Propranolol as first-line treatment for rapidly proliferating infantile haemangiomas. J Plast Reconstr Aesthet Surg 2011; 64(4): 445–451.

74. Truong MT, Perkins JA, Messner AH et al. Propranolol for the treatment of airway hemangiomas: a case series and treatment algorithm. Int J Pediatr Otorhinolaryngol 2010; 74(9): 1043–1048.

75. Mazereeuw-Hautier J, Hoeger PH, Benlahrech S et al. Efficacy of propranolol in hepatic infantile hemangiomas with diffuse neonatal hemangiomatosis. J Pediatr 2010; 157(2): 340–342.

76. Vanlander A, Decaluwe W, Vandelanotte M et al. Propranolol as a novel treatment for congenital visceral haemangioma. Neonatology 2010; 98(3): 229–231.

77. Löffler H, Kosel C, Cremer H et al. Propranolol therapy to treat problematic hemangiomas: a new standard therapy makes its debut. Hautarzt 2009; 60(12): 1013–1016.

78. Lawley LP, Siegfried E, Todd JL. Propranolol treatment for hemangioma of infancy: risks and recommendations. Pediatr Dermatol 2009; 26(5): 610–614.

79. Mihál V, Novák Z, Hůlková E et al. Kdy je indikována léčba infantilních hemangiomů propranololem? Pediatr Praxi 2011; 12(2): 108–110.

80. Mihál V, Michálková K Novák Z. Kapilární hemangiom sleziny. Pediatr praxi 2003; 4: 214–216.

81. Justová E, Pazdera J Michál V. Systémové terapie interferonem u nemocných s nádory z vazoformní tkáně a infantilní fibromatózy. Čes Slov Pediat 1998; 143(2): 53–55.

82. Justová E, Mihál V, Pazdera J. Sklerotizace v terapii nádorů z vazoformativní tkáně Pediatr Praxi 2007; 3: 173–175.