eMedicine Specialties > Pulmonology > Idiopathic Lung Disorders

Milroy Disease: Treatment & Medication

Author: Raphael J Kiel, MD, Associate Professor of Medicine, Wayne State University School of Medicine; Consulting Staff, Infectious Diseases Division, William Beaumont Hospital
Contributor Information and Disclosures

Updated: Oct 16, 2008

Treatment

Medical Care

Treatment of patients with hereditary lymphedema is primarily directed against the prevention of infection and the control of local complications of limb swelling. Studies in mice, however, suggest that induced overexpression of VEGFR3 ligands stimulate the growth of functional lymphatic vessels.12 An increase in lymphatics would benefit patients with primary and secondary lymphedema.

  • Exercise and elevation of the extremity promote movement of fluid away from the lower extremity.
  • Elastic stockings and bandages are applied in a gradient fashion, with the highest compression distally and no constriction points.
  • Gentle massage or pneumatic compression can be used.
  • Proper skin hygiene and use of skin moisturizers prevents drying and fissuring of skin and subsequent bacterial skin infections.
  • Use an antistreptococcal antibiotic to treat recurrent cellulitis. Prophylactic antibiotic therapy, such as benzathine penicillin in low doses, may be used to prevent intermittent cellulitis. Antibiotics directed at prophylaxis should have good activity against Streptococcus pyogenes.
  • No medication treats or prevents Milroy disease. Complications of this disease, including cellulitis, bacteremia, and chylothorax, are treated as required. Benzopyrones, such as coumarin or diosmin, may stimulate proteolysis of tissue proteins.

Surgical Care

  • Several surgical methods have been attempted to benefit patients with Milroy disease, but none has achieved lasting success.
  • Excision of the fibrotic subcutaneous tissues with coverage by split-thickness skin grafts has been described.
  • Pedicular transfer of skin with healthy lymphatics to the affected limb and anastomosis to existing lymphatic channels has been tried without much success.

Consultations

  • Consultation with an infectious disease specialist is indicated for the treatment of recurrent cellulitis.
  • In the future, consultation with a geneticist will provide insights into familial inheritance patterns.

Activity

Encourage patients to exercise after a graded support is applied to the involved extremity.

Medication

No medication treats or prevents Milroy disease. Complications of this disease, including cellulitis, bacteremia, and chylothorax, are treated as required. Antistreptococcal antibiotics (eg, cefazolin, clindamycin) can be used to treat cellulitis. Monthly penicillin G benzathine injections may be required to prevent recurrent cellulitis.

Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of this clinical setting.


Cefazolin (Ancef)

First-generation semisynthetic cephalosporin that arrests bacterial cell wall synthesis, inhibiting bacterial growth. Primarily active against skin flora, including Staphylococcus aureus. Typically used alone for skin and skin-structure coverage. IV and IM dosing regimens are similar.

Adult

250 mg to 2 g IV/IM q6-12h, depending on severity of infection; not to exceed 12 g/d

Pediatric

25-100 mg/kg/d IV/IM divided q6-8h, depending on severity of infection; not to exceed 6 g/d

Probenecid prolongs effect; coadministration with aminoglycosides may increase renal toxicity; may yield false-positive urine-dip test results for glucose

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment; superinfections and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy


Clindamycin (Cleocin)

Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (but not enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Adult

150-450 mg/dose PO q6-8h; not to exceed 1.8 g/d; 600-1200 mg/d IV/IM divided q6-8h, depending on degree of infection

Pediatric

8-20 mg/kg/d PO as hydrochloride and 8-25 mg/kg/d PO as palmitate divided tid/qid; 20-40 mg/kg/d IV/IM divided tid/qid

Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects; antidiarrheals may delay absorption

Documented hypersensitivity; regional enteritis, ulcerative colitis, hepatic impairment, antibiotic-associated colitis

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in patients with severe hepatic dysfunction; no adjustment necessary in patients with renal insufficiency; associated with severe and possibly fatal colitis by allowing overgrowth of Clostridium difficile


Penicillin G benzathine (Bicillin)

Interferes with synthesis of cell wall mucopeptides during active multiplication, which results in bactericidal activity. Used to treat syphilis and for prophylaxis of recurrent streptococcal infections.

Adult

1.2 million U IM qmo

Pediatric

25,000-50,000 U/kg IM qmo; not to exceed 1.2 million U/dose

Probenecid can increase effectiveness by decreasing clearance; coadministration with tetracyclines can decrease effectiveness

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients with impaired renal function

Anticoagulants

May stimulate proteolysis of tissue proteins.


Warfarin (Coumadin)

Interferes with hepatic synthesis of vitamin K–dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Tailor dose to maintain INR of 2-3.

Adult

5-15 mg/d PO for 2-5 d; adjust dose according to desired INR

Pediatric

0.05-0.34 mg/kg/d PO; adjust dose according to desired INR

Drugs that may decrease anticoagulant effects include griseofulvin, carbamazepine, glutethimide, estrogens, nafcillin, phenytoin, rifampin, barbiturates, cholestyramine, colestipol, vitamin K, spironolactone, oral contraceptives, and sucralfate; medications that may increase anticoagulant effects include oral antibiotics, phenylbutazone, salicylates, sulfonamides, chloral hydrate, clofibrate, diazoxide, anabolic steroids, ketoconazole, ethacrynic acid, miconazole, nalidixic acid, sulfonylureas, allopurinol, chloramphenicol, cimetidine, disulfiram, metronidazole, phenylbutazone, phenytoin, propoxyphene, sulfonamides, gemfibrozil, acetaminophen, and sulindac

Documented hypersensitivity; severe liver or kidney disease; open wounds or GI ulcers

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Do not switch brands after achieving therapeutic response; caution in patients with active tuberculosis or diabetes; patients with protein C or S deficiency are at risk of developing skin necrosis

More on Milroy Disease

Overview: Milroy Disease
Differential Diagnoses & Workup: Milroy Disease
Treatment & Medication: Milroy Disease
Follow-up: Milroy Disease
References
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References

  1. Levinson KL, Feingold E, Ferrell RE, Glover TW, Traboulsi EI, Finegold DN. Age of onset in hereditary lymphedema. J Pediatr. Jun 2003;142(6):704-8. [Medline].

  2. Dahlberg PJ, Borer WZ, Newcomer KL, Yutuc WR. Autosomal or X-linked recessive syndrome of congenital lymphedema, hypoparathyroidism, nephropathy, prolapsing mitral valve, and brachytelephalangy. Am J Med Genet. Sep 1983;16(1):99-104. [Medline].

  3. Wheeler ES, Chan V, Wassman R, Rimoin DL, Lesavoy MA. Familial lymphedema praecox: Meige's disease. Plast Reconstr Surg. Mar 1981;67(3):362-4. [Medline].

  4. Namnyak S, Adhami Z, Toms G, Jenks P. Pasteurella multocida septicaemia in Milroy's disease. J Infect. Sep 1995;31(2):175-6. [Medline].

  5. Irrthum A, Karkkainen MJ, Devriendt K, Alitalo K, Vikkula M. Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase. Am J Hum Genet. Aug 2000;67(2):295-301. [Medline].

  6. Butler MG, Dagenais SL, Rockson SG, Glover TW. A novel VEGFR3 mutation causes Milroy disease. Am J Med Genet A. Jun 1 2007;143A(11):1212-7. [Medline].

  7. Evans AL, Brice G, Sotirova V, Mortimer P, Beninson J, Burnand K, et al. Mapping of primary congenital lymphedema to the 5q35.3 region. Am J Hum Genet. Feb 1999;64(2):547-55. [Medline].

  8. Offori TW, Platt CC, Stephens M, Hopkinson GB. Angiosarcoma in congenital hereditary lymphoedema (Milroy's disease)--diagnostic beacons and a review of the literature. Clin Exp Dermatol. Mar 1993;18(2):174-7. [Medline].

  9. Ghalamkarpour A, Morlot S, Raas-Rothschild A, Utkus A, Mulliken JB, Boon LM, et al. Hereditary lymphedema type I associated with VEGFR3 mutation: the first de novo case and atypical presentations. Clin Genet. Oct 2006;70(4):330-5. [Medline].

  10. Wu JJ, Wagner AM. Verruciform xanthoma in association with milroy disease and leaky capillary syndrome. Pediatr Dermatol. Jan-Feb 2003;20(1):44-7. [Medline].

  11. Bollinger A, Amann-Vesti BR. Fluorescence microlymphography: diagnostic potential in lymphedema and basis for the measurement of lymphatic pressure and flow velocity. Lymphology. Jun 2007;40(2):52-62. [Medline].

  12. Karkkainen MJ, Saaristo A, Jussila L, Karila KA, Lawrence EC, Pajusola K, et al. A model for gene therapy of human hereditary lymphedema. Proc Natl Acad Sci U S A. Oct 23 2001;98(22):12677-82. [Medline].

  13. Albornoz MA, Myers AR. Recurrent septic arthritis and Milroy's disease. J Rheumatol. Nov 1988;15(11):1726-8. [Medline].

  14. American Medical Association. William Forsyth Milroy (1855-1942): hereditary edema of the lower legs. JAMA. Apr 8 1968;204(2):166. [Medline].

  15. Baginski D, Telang GH, Koblenzer PJ. Answers to Self-Assessment Examination of the American Academy of Dermatology. J Am Acad Dermatol. 1997;37:146-7.

  16. Bollinger A. Microlymphatics of human skin. Int J Microcirc Clin Exp. Feb 1993;12(1):1-15. [Medline].

  17. Bollinger A, Isenring G, Franzeck UK, Brunner U. Aplasia of superficial lymphatic capillaries in hereditary and connatal lymphedema (Milroy's disease). Lymphology. Mar 1983;16(1):27-30. [Medline].

  18. Broström LA, Nilsonne U, Kronberg M, Söderberg G. Lymphangiosarcoma in chronic hereditary oedema (Milroy's disease). Ann Chir Gynaecol. 1989;78(4):320-3. [Medline].

  19. Cohen SR, Payne DK, Tunkel RS. Lymphedema: strategies for management. Cancer. Aug 15 2001;92(4 Suppl):980-7. [Medline].

  20. Edwards EA. Cutaneous Changes in Peripheral Vascular Disease. In: Fitzpatrick T, Eisen A, Wolff K, Freedberg I, Austen KF, eds. Dermatology in General Medicine. 2nd ed. New York, NY: McGraw-Hill; 1979:1392-5.

  21. Ersek RA, Danese CA, Howard JM. Hereditary congenital lymphedema (Milroy's disease). Surgery. Nov 1966;60(5):1098-103. [Medline].

  22. Farhud DD, Farhud I, Walizadeh GR, Djaber-Ansari M. Congenital hereditary lymphedema (Nonne/Milroy). Padiatr Padol. 1989;24(4):305-7. [Medline].

  23. Ferrell RE, Levinson KL, Esman JH, Kimak MA, Lawrence EC, Barmada MM, et al. Hereditary lymphedema: evidence for linkage and genetic heterogeneity. Hum Mol Genet. Dec 1998;7(13):2073-8. [Medline].

  24. From L. Vascular Neoplasms, Pseudoneooplasms and Hyperplasias. In: Fitzpatrick T, Eisen A, Wolff K, Freedberg I, Austen KF, eds. Dermatology in General Medicine. 2nd ed. New York, NY: McGraw-Hill; 1979:736-7.

  25. Gregl A, von Heyden D, Jentsch F, Yu D. [Primary lymphedema]. Z Lymphol. Jul 1983;7(1):21-8. [Medline].

  26. Margileth A. Dermatologic Conditions Neonatology. In: Avert GB, ed. Pathophysiology and Management of the Newborn. 3rd ed. Philadelphia, Pa: JB Lippincott; 1987:1253-4.

  27. Mehta SD, Robinson RJ, Bern SA. Pedal manifestations of Milroy's disease. J Am Podiatr Med Assoc. Aug 1996;86(8):400-2. [Medline].

  28. Offret H, Labrune B. [Primary conjunctival-palpebral lymphedema and Milroy disease]. J Fr Ophtalmol. 1994;17(11):679-82. [Medline].

  29. Pap Z, Biró T, Szabó L, Papp Z. Syndrome of lymphoedema and distichiasis. Hum Genet. 1980;53(3):309-10. [Medline].

  30. Partsch H, Urbanek A, Wenzel-Hora B. The dermal lymphatics in lymphoedema visualized by indirect lymphography. Br J Dermatol. Apr 1984;110(4):431-8. [Medline].

  31. Rock A, Camitta BM. The Lymphatic System. In: Behrman RE, Kliegman RM, Jensen HB, eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pa: WB Saunders; 2000:1528.

  32. Ryan TJ, Champion RH. Disorders of Lymphatic Vessels. In: Champion RH, Ebling FJG, Burton JL, eds. Textbook of Dermatology. 5th ed. Oxford, England: Oxford Blackwell Scientific; 1992:2018-23.

  33. Sigstad H, Aagenaes O, Bjorn-Hansen RW, Rootwelt K. Primary lymphoedema combined with hereditary recurrent intrahepatic cholestasis. Acta Med Scand. Sep 1970;188(3):213-9. [Medline].

  34. St Louis JD, McCann RL. Lymphatic System. In: Townsend CM Jr, ed. Sabiston Textbook of Surgery. 16th ed. Philadelphia, Pa: WB Saunders; 2001:1446-51.

  35. Tiwari A, Cheng KS, Button M, Myint F, Hamilton G. Differential diagnosis, investigation, and current treatment of lower limb lymphedema. Arch Surg. Feb 2003;138(2):152-61. [Medline].

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Further Reading

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Keywords

Milroy disease, congenital lymphedema, lymphedema congenita, noninfectious hereditary elephantiasis, autosomal dominant lymphedema, lymphatic obstruction, fibrosis, cellulitis, Meige disease, lymphedema tarda, lymphedema praecox

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Contributor Information and Disclosures

Author

Raphael J Kiel, MD, Associate Professor of Medicine, Wayne State University School of Medicine; Consulting Staff, Infectious Diseases Division, William Beaumont Hospital
Raphael J Kiel, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and American Geriatrics Society
Disclosure: Nothing to disclose.

Medical Editor

Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St. Boniface General Hospital
Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, and World Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Gregg T Anders, DO, Medical Director, Great Plains Regional Medical Command , Brook Army Medical Center; Clinical Associate Professor, Department of Internal Medicine, Division of Pulmonary Disease, University of Texas Health Science Center at San Antonio
Gregg T Anders, DO is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society
Disclosure: Nothing to disclose.

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