|Year : 2014 | Volume
| Issue : 6 | Page : 790-792
Atypical Nonne-Milroy syndrome: Complicated with chylous effusion
Rupam Kumar Ta1, Kaushik Saha1, Mrinmoy Mitra2, Arnab Saha1, Arnab Roy1, Pratik Barma1
1 Department of Pulmonary Medicine, Burdwan Medical College, Burdwan, India
2 Calcutta National Medical College, Kolkata, West Bengal, India
|Date of Web Publication||18-Nov-2014|
Department of Pulmonary Medicine, Burdwan Medical College, Burdwan, Rabindra Pally, 1st Lane, P. O - Nimta, Kolkata - 700 049, West Bengal
Source of Support: None, Conflict of Interest: None
Nonne-Milroy syndrome is a rare primary lymphedema characterized by firm non-pitting edema of the lower extremities of the whole leg or may be limited to the feet or toes since birth or infancy. We are reporting a 51-year-old male who presented with dry cough for the previous 7 months and dyspnea for the previous 4 months due to bilateral chylous effusion and that was associated with firm edema of the lower extremities, was waxing and waning since birth. Duplex ultrasound of the lower limbs showed patent blood vessels. Lymphoscintigraphy demonstrated aplasia of the lymphatics in both lower limbs. The patient was diagnosed as primary lymphedema or Nonne-Milroy syndrome after excluding other congenital causes of primary edema. He was treated by bilateral pleurodesis with tetracycline for his chylous effusion and no recurrence was observed after 1 year of follow-up.
Keywords: Chylous effusion, Nonne-Milroy syndrome, primary lymphedema
|How to cite this article:|
Ta RK, Saha K, Mitra M, Saha A, Roy A, Barma P. Atypical Nonne-Milroy syndrome: Complicated with chylous effusion. Med J DY Patil Univ 2014;7:790-2
|How to cite this URL:|
Ta RK, Saha K, Mitra M, Saha A, Roy A, Barma P. Atypical Nonne-Milroy syndrome: Complicated with chylous effusion. Med J DY Patil Univ [serial online] 2014 [cited 2021 Jan 17];7:790-2. Available from: https://www.mjdrdypu.org/text.asp?2014/7/6/790/144886
| Introduction|| |
Lymphedema is the abnormal collection of fluid in the subcutaneous tissue due to dysfunction of the lymphatic system. Nonne-Milroy lymphedema (also known as hereditary lymphedema I and Milroy disease) is a developmental disorder of the lymphatic system that leads to a disfiguring swelling of the extremities.  Persistent and painless swelling of one or both lower limbs is usually the first sign of lymphedema in Milroy disease. Swelling is often present at birth or during infancy. Chylothorax, chylousascitis and chylopericardium are rarely associated with lymphedema and tend to appear between 20 and 40 years of age. These characterize a variant termed atypical Nonne-Milroy syndrome More Details.  In this article, we report a newnovel case of atypical Nonne-Milroy syndrome in the light of the relevant literature.
| Case Report|| |
A 51-year-old male patient presented with swelling of both lower limbs and scrotum since birth, with exacerbations and remissions of symptoms. Since then, several physicians were consulted and he was treated with several drugs and different supportive measures like elevation of legs at bedtime, massage, crepe bandage, etc.; however, the swelling did not subside but rather progressed gradually. He was suspected as a case of lymphedema 30 years back and was treated conservatively with pressure bandages, but the edema persisted with waxing and waning. No further investigation was carried out at that time. The patient presented to our outpatient clinicdeveloped with dry cough for the previous 7 months along with persistent and progressive dyspnea for the previouslast 4 months. He had no history of chest pain, fever or hemoptysis. He hadhas two brothers with a history of a similar type of leg swelling. On examination, non-pitting edema was present in both lower limbs that extended proximally up to the scrotum [Figure 1]a. Kaposi-Stemmer sign (fold of skin at the base of the second toe on the dorsal foot cannot be pinched) was positive and it was consistent with lymphedema [Figure 1]b. The patient was tachypneic (respiratory rate was 34/min). There was stony dullness with diminished vesicular breath sound present in the mammary, axillary, infra-axillary, lower inter-scapular and infra-scapular areas on the left side and infra-axillary and infra-scapular areas on the right side of his chest. His Mantoux test and immunochromatographic card test (ICT) for Filaria was negative and ESR was not raised. Chest X-ray showed bilateral pleural effusion, more on the left side [Figure 2]a. Diagnostic thoracentesis was performed from the left side. Pleural fluid was milky in color. Examination for gram stain, C/S and acid fast bacilli was negative. Fluid study also revealed chyle as there was a presence of chylomicrons and the triglyceride level was 210 mg/dL. Duplex ultrasound of the lower limbs showed patent blood vessels. Echocardiography was normal. Lymphoscintigraphy demonstrated aplasia of the lymphatics in both lower limbs [Figure 3]. Inter-costal drainage was given on the left side and pleurodesis was performed with tetracycline. Similar management was performed on the right side as the pleural effusion on that side also revealed chylothorax. On repeat chest X-ray after 3 months, there was bilateral pleural thickening without any evidence of effusion [Figure 2]b. For leg edema, the treatment advised to the patient was exercise, gradient pressure garments and massage therapy. The patient is now clinically stable except for the edema in both lower limbs.
|Figure 1: Presence of non-pitting edema in both lower limbs (a) with Kaposi– Stemmer sign (fold of skin at the base of the second toe on the dorsal foot cannot be pinched) was positive and it was consistent|
with lymphedema (b)
Click here to view
|Figure 2: Chest X-ray showing bilateral pleural effusion, more on the left side (a) and chest X-ray after 3 months of plerodesis showing bilateral pleural thickening (b)|
Click here to view
|Figure 3: Lymphoscintigraphy showing aplasia of the lymphatics in both lower limbs|
Click here to view
| Discussion|| |
Lymphatics play an important role in maintaining interstitial fluid balance. The development of the human lymphatic system begins in the sixth to seventh weeks of embryonic life. Lymphangiogenesis is tightly regulated by growth factors and intercellular and cell extra cellular matrix (ECM) signaling mechanisms. Lymphedema is caused by an increase in interstitial protein-rich fluid that is due to insufficient transport and drainage of the lymphatics. The majority of the patients with lymphedema can be diagnosed by thorough history taking, physical examination and ultrasound.  Isotopic lymphoscintigraphy is generally considered as the gold standard for the diagnosis of lymphedema as the procedure is minimally invasive and harmless to the lymphatic endothelium. , Direct lymphography, computed tomography imaging and magnetic resonance imaging are also good alternatives. There are two major types of lymphedema: Primary (idiopathic) and secondary (acquired), the latter with a known pathologic alteration like obstruction or damage of the lymphatics.  Primary lymphedema can be either isolated or can be as a part of different syndromes. As our patient had congenital lymphedema, primary lymphedema was diagnosed. There are several genetic causes of primary lymphedema, like Turner's syndrome, Noonan syndrome, Yellow nail syndrome, Lymphedema- distichiasis syndrome, Hypotrichosis-lymphedema - telangiectasia syndrome and many others. As our patient had congenital primary lymphedema without any of the characteristic features of these syndromes described above, Milroy disease was diagnosed. Milroy disease is a relatively rare form of primary lymphedema that is usually caused by a mutation in the FLT4/VEGRF3 gene.  The superficial lymphatics of the affected edematous areas in patients with Milroy disease are thought to be aplastic or hypoplastic. , In some individuals with Milroy disease, chylothorax can develop in between the second and fourth decades of age. The exact mechanism of development of pleural effusion in patients with hereditary lymphedema is unknown. It is suspected to result from a basic defect in the development of lymphatic vessels. But, the cause for why thoracic involvement presents later in life is unclear.  Nonne-Milroy disease with chylothorax, as in our case, is known as atypical Nonne-Milroy syndrome. The leg edema and thoracic involvement tends to worsen over time. For long-standing limb edema, the treatment is focused on non-operative options like special exercise, manual lymphedema drainage, compression therapy and massages.  We also advised our patient with these conservative therapeutic options. In this case, the pleural effusion was chylothorax, and this was definitely due to lymphatic obstruction. Also, the chance of recurrences was very high. That is why we treated the chylothorax with pleurodesis. As lymphedema is a chronic disease, life-long follow-up is necessary for preventing complications and monitoring the effects of treatment. Our patient is also on regular follow-up.
| References|| |
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.1998;7:2073-8.
Leg-Sagie A, Hamani Y, Raas-Rothschild A, Yagel S, Anteby EY. Prenatal ultrasonographic diagnosis of atypical Nonne-Milroy lymphedema. Ultrasound Obstet Gynecol 2003;21:72-4.
Kitsiou-Tzeli S, Vrettou C, Leze E, Makrythanasis P, Kanavakis E, Willems P. Milroy's primary congenital lymphedema in a male infant and review of the literature. In Vivo 2010;24:309-14.
Tamella T, Alitalo K. Lympangiogenesis: Molecular mechanisms and future promise. Cell 2010;140:470-6.
Vignes S, Coupé M, Baulieu F, Vaillant L; Groupe Recommandations de la Société Française de Lymphologie. Limb lymphedema: Diagnosis, explorations, complications. French Lymphology Society. J Mal Vasc 2009;34:314-22.
Ghalamkarpour A, Holnthoner W, Saharinen P, Boon LM, Mulliken JB, Alitalo K, et al
. Recessive primary congenital lymphoedema caused by a VEGFR3 mutation. J Med Genet 2009;46:399-404.
Bollinger A, Amann-Vesty BR. Fluorescent microlymphography: Diagnostic potential in lymphedema and basis for the measurement of lymphatic pressure and flow velocity. Lymphology 2007;40:52-62.
[Figure 1], [Figure 2], [Figure 3]