ABSTRACT

Corresponding Author:
Dr. Afthab Jameela Wahab,
R35, Flat 14, Nilgiri Apartments,
T S Krishna Nagar, Mugappair,
Chennai- 600037.
E-mail: afthabjameela@hotmail.com

ABSTRACT

A ten-year old girl presented with unilateral swelling of right half of her body since birth. She developed itchy, oozing, painful skin lesions over right lower leg for the past three months. Clinical examination and investigations revealed unilateral lymphoedema with elephantiasis nostras verrucosa cutis and visceral involvement in the form of pericardial effusion, ascites and intestinal lymphangiectasia. She was diagnosed as a case of multisegmental lymphatic dysplasia with systemic involvement. We report this rare case of primary lymphoedema, highlighting the approach to a case of primary lymphedema.

KEYWORDS

Primary Lymphedema, Multisegmental Lymphatic Dysplasia, Lymphangiectasia.

INTRODUCTION

Primary lymphoedema results from an inherent developmental abnormality of the lymphatic system. Multisegmental Lymphatic Dysplasia with Systemic Involvement (MLDSI), a subtype of primary lymphedema, is characterized by a segmental pattern of lymphoedema affecting different body parts associated with systemic involvement.

CASE REPORT

A 10-year-old girl, who had hypertrophy of the entire right half of the body since birth presented with painful, itchy, oozing skin lesion over her right lower leg of three months duration (Figure-1).

She was the second child of non-consanguineous parents with a birth weight of 6.5kg, delivered by caesarean section. The hemihypertrophy had increased proportionately to her growth, uninfluenced by postural changes. She had developed recurrent cellulitis over her right leg swelling for which she was on intermittent treatment.

Patient gives history of recurrent upper respiratory tract infections. There was no history suggestive of cardiovascular, gastrointestinal and central nervous system involvement clinically.

The patient’s vital signs, general and systemic examination was normal. There was increased girth of right half of face and body and right limbs indicating right unilateral lymphedema with soft tissue hypertrophy. There was no warmth or tenderness and no length discrepancy between right and left upper and lower limbs.

The swelling over the right lower limb was non-pitting, non-pulsatile, non-reducible and non-compressible. There was no bruit, thrill or varicose veins. The dorsal aspect of lower third of right leg and foot showed elephantiasis nostras with hyperkeratotic, rugose, verrucous plaque of size 20x15cm with fissuring, crusting and erosion and milky white discharge (Figure-2). Kaposi-Stemmer’s sign was positive. There were multiple discrete vesicles over right lumbar region, left lower back and right earlobe. Gait, IQ, sensory and motor examination was normal.

Routine hemogram, urine analysis, liver and renal function tests and lipid profile were normal. Ultrasonography revealed pericardial effusion and ascites. Oesophagogastroduodenoscopy showed inflamed duodenal bulb, nodules in the entire duodenum and granular white milky spots from bulb to second part of duodenum-D2.

Histopathology of biopsies taken from verrucous lesion showed pseudoepitheliomatous hyperplasia and dermal dilated lymphatic vessels (Figure-3), truncal vesicles showed microcystic lymphatic malformations and D2/D3 was consistent with intestinal lymphangiectasia. Doppler study of right limbs was normal with no evidence of vascular malformations. Ophthalmic examination revealed refractory error in the right eye. Chromosomal analysis showed XX genotype. Two attempts at MRI lymphangiography failed as the child did not cooperate.

The patient was diagnosed as Multisegmental Lymphatic Dysplasia with systemic involvement. The secondarily infected acute eczema was treated with appropriate antibiotics after culture and sensitivity. She was then referred to Surgical Gastroenterology for management of intestinal lymphangiectasia.

Fig. 1: Right-sided Unilateral Lymphoedema

Fig. 2: Elephantiasis Nostras Verrucosa Cutis

Fig. 3: Histopathology showing Pseudoepitheliomatous Hyperplasia (a) and Dilated Lymphatic Vessels (b, c, d)

DISCUSSION

Lymphoedema is defined as swelling of tissues resulting from accumulation of lymph caused by inadequate drainage. It may be primary or secondary. Primary lymphedema implies an intrinsic developmental or functional fault in lymph drainage.¹ Secondary lymphedema occurs when previously normal lymphatics suffer from an external insult such as disease, infection, tumors, trauma or surgery with loss of functional capability.¹

Primary lymphoedema may be classified into four types.²

1. Isolated primary lymphedema.
2. Primary lymphedema associated with systemic or visceral involvement.
3. Primary lymphedema associated with disturbed growth/ cutaneous/vascular anomalies.
4. Primary lymphedema as part of syndromes.

Isolated primary lymphoedema is lymphoedema confined to skin and soft tissue only. It may be of congenital onset (<1 year) or of late onset (>1 year), further subtyping depending on the limb or segments involved.

 Milroy’s disease, an autosomal dominant disease caused by failure of lymphangiogenesis secondary to inactivation of VEGFR-3 with familial, bilateral below-knee lymphoedema.³

Primary lymphedema as a part of syndromes

Turner’s syndrome 45XO Chromosomal testing is essential in neonates/children with primary lymphoedema.

Noonan’s syndrome PTPN11.

Hypotrichosis-lymphoedema -telangiectasia syndrome

SOX18.

Microcephaly-lymphoedema–chorioretinal dysplasia KIF11.⁸

Cholestasis- lymphoedema syndrome (Aagenaes’s syndrome).

Yellow nail syndrome.

CONCLUSION

An algorithmic approach to evaluate a case of primary lymphoedema would be to first assess the extent of lymphedema, systemic/visceral lymphatic involvement and then to exclude associated syndromes, growth disturbances, vascular/cutaneous anomalies. In our case associated syndromes were ruled out by clinical examination and chromosomal analysis. Further investigations excluded vascular malformations, cutaneous anomalies and growth disturbances. Systemic lymphatic involvement (intestinal lymphangiectasia, pericardial effusion, ascites) ruled out isolated primary lymphoedema. Unilateral congenital lymphoedema with normal intelligence excluded GLD, confirming the diagnosis of “Multisegmental lymphatic dysplasia with systemic involvement.” This rare-case report attempts at highlighting an algorithmic approach in evaluating primary lymphoedema.

REFERENCES

1.    Mortimer PS (1998). The pathophysiology of lymphedema. Cancer, 83:2798–2802.
2.    Connell FC, et al. The classification and diagnostic algorithm for primary lymphatic dysplasia: an update from 2010 to include molecular findings. Clin Genet 2013;84:303–314.
3.    Rrthum A, Karkkainen MJ, Devriendt K, Alitalo K, Vikkula M. Congenital Hereditary Lymphedema Caused by a Mutation That Inactivates VEGFR3 Tyrosine Kinase. American Journal of Human Genetics.
2000;67(2):295-301.
4.    Mangion et al., 1999. A gene for lymphoedema-distichiasis maps to 16q24.3. am j hum genet, vol 65, 1999, pp427-432.
5.    Meige H. Dystrophie oedemateuse héréditaire. Presse Méd 1898;6:341–3.
6.    Alders M, et al. Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans.  Nat Genet 2009;41:1272–1274.
7.    Carlton A, St Elkington JC, Greenfi eld JG, et al. Maffucci’s syndrome. QJM 1942;11:203–8.
8.    Ostergaard P, Simpson MA, Mendola A, et al. Mutations in KIF11 Cause Autosomal-Dominant Microcephaly Variably Associated with Congenital Lymphedema and Chorioretinopathy. American Journal of Human Genetics.2012;90(2):356-362. doi:10.1016/j.ajhg.2011.12.018.