Paediatric lower limb primary lymphedema: a case report of conservative management

Introduction

Primary lymphedema (PL) is a rare and often underrecognized condition in the paediatric population. Its presentation can be subtle and nonspecific, frequently leading to misdiagnosis or delayed diagnosis. In children, unilateral lower limb swelling is more commonly attributed to trauma, infection, or inflammatory conditions such as juvenile idiopathic arthritis (JIA). This diagnostic ambiguity can result in inappropriate treatment and prolonged patient discomfort (1). Our case underscores the diagnostic complexity of PL, particularly when it presents with recurrent episodes of cellulitis.

This case is unique in that it highlights the diagnostic journey of a previously healthy 9-year-old boy who was treated for JIA without clinical improvement, only to later be diagnosed with PL following a second episode of cellulitis. While this case report does not add new knowledge regarding PL, it highlights the importance of maintaining a broad differential diagnosis when evaluating persistent unilateral limb swelling in children. By sharing this case, we aim to raise awareness among clinicians about the varied presentations of PL and the need for early recognition to prevent complications and improve long-term outcomes. We present this article in accordance with the CARE reporting checklist (available at https://pm.amegroups.com/article/view/10.21037/pm-25-84/rc).

Case presentation

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient’s legal guardians for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal. A fully immunized 9-year-old boy presented to the emergency room with a day-long history of fever and worsening erythema and swelling of his left lower leg. He had a previous admission for cellulitis overlying the left medial malleolus a year prior. During that admission, he was treated with antibiotics and discharged, but continued to experience painless swelling of the left foot and ankle, without restriction to activity. He was subsequently referred to paediatric rheumatology, where testing for antinuclear antibodies (ANA), human leukocyte antigen B-27 (HLA-B27) and rheumatoid factor all returned negative. He was diagnosed with JIA and was started on methotrexate which did not reduce the swelling. Until a day prior to his presentation to our hospital, the patient remained in overall good health.

The patient had no history of trauma, fevers, weight loss, travel, tick bites, recent sore throat, or diarrheal illness. He denied any sick contacts. The patient was born at term after an uncomplicated pregnancy and delivery. Family history was unremarkable for any rheumatologic or musculoskeletal disorders. Most importantly, family history was negative for primary lymphedema.

On physical examination, the patient appeared well and was afebrile with stable vital signs. Pitting edema was observed in the left lower extremity, extending up to the mid-tibia, accompanied by erythema at the left medial malleolus. The patient experienced pain upon palpation of that malleolus. He also had decreased range of motion of his left ankle. The neurovascular examination of the lower limb did not reveal any significant abnormality.

The patient exhibited normal range of motion in all other joints, with no signs of swelling. There was no sensitivity to light, presence of lymphadenopathy, oral ulcers, malar rash, or other rashes. The abdomen was soft and non-tender, and there were neither hepatomegaly nor splenomegaly.

The patient was admitted for further workup and management. The patient’s complete blood count revealed neutrophilia with a count of 11.9×10³/L [normal range, (1.5–8.5)×10³/L]. Inflammatory markers were significantly elevated with a C-reactive protein (CRP) level of 195 mg/L (normal range is less than 5 mg/L) and an erythrocyte sedimentation rate (ESR) of 23 mm/hour (normal range is less than 10 mm/hour). Blood cultures yielded no growth, and liver and renal function tests were normal. An ankle ultrasound showed signs of probable cellulitis without deep venous thrombosis. X-ray imaging of the ankle and foot showed no fractures or bony changes, while magnetic resonance imaging (MRI) of the ankle revealed subcutaneous edema and cellulitis of the ankle and foot but ruled out osteomyelitis or septic arthritis. Treatment with cefazolin was initiated.

The paediatric rheumatology service assessed the patient and determined that an underlying inflammatory disorder was unlikely. To rule out the potential of an obstructive cause of unilateral edema, such as a pelvic tumour or lymphoma, an abdominal ultrasound was performed, which yielded negative results. A radionuclide lymphangiogram was conducted to evaluate the lymphatic system. The imaging revealed slow migration superiorly in the left foot compared to the right, accompanied by a noticeable dermal backflow within the left distal extremity (Figure 1). Based on clinical assessment and nuclear imaging findings, the patient was diagnosed with PL.

Figure 1 This radionuclide lymphoscintigraphy image shows the prompt migration of tracer up to the right leg compared to the slow migration in the left leg.

The patient showed improvement in the left lower leg cellulitis with antibiotics. He was initially treated with intravenous cefazolin which was transitioned to oral cephalexin at discharge. His CPR dropped down to 32.8 mg/L by discharge on day 8 post-admission. Considering his diagnosis of PL, the patient was started on combined decongestive therapy (CDT) and underwent a follow-up assessment with paediatric general surgery at 1 year. Although the edema persisted as expected with PL, the patient continued to have a full range of motion and remained active, participating in sports without any restriction. One further episode of cellulitis occurred 2 years following diagnosis, requiring admission and a 3-day course of parenteral antibiotics, followed by a transition to oral antimicrobial therapy. Figure 2 shows a timeline of this patient’s course.

Figure 2 Timeline of the patient’s presentation. CDT, combined decongestive therapy.

Discussion

The differential diagnosis for unilateral lower extremity edema includes many etiologies. Systemic factors including hypoalbuminemia, fluid overload and myxedema should be taken into consideration (1). Additionally, it is essential to investigate other potential causes such as deep vein thrombosis, venous insufficiency, congenital venous malformations, pelvic obstructive tumors, lipedema, as well as lymphedema (2). Lymphedema refers to the localized accumulation of lymphatic fluid in the interstitial compartment due to impaired lymphatic drainage (1,3).

Lymphedema can be either primary or secondary in nature. Secondary lymphedema occurs when lymphatic drainage is impaired due to a factor external to the lymphatic system, such as infection or surgery (3). On the other hand, PL is characterized by developmental vascular lymphatic anomaly resulting from genetic mutations that impair the development of lymphatic vessels. The prevalence of PL is approximately of 1 in 100,000 and typically presents during childhood but can present at any age (1).

PL is classified into three types based on the age of onset: congenital lymphedema (presenting at or soon after birth), lymphedema praecox (occurring around puberty, consistent with our patient’s case), and lymphedema tarda, which manifests in adulthood (4). PL in the lower limbs presents initially with a sensation of leg heaviness, discomfort, pitting edema, dimpled skin (peau d’orange) and eventual skin thickening and fibrosis. Complications of PL include recurrent infections such as lymphangitis or cellulitis, limitations in range of motion and negative body image (1). In our patient, the repeated episode of cellulitis prompted further investigation, leading to the discovery of his underlying abnormality. This case is unique in terms of the presentation that was misdiagnosed comma leading to unnecessary treatments and delayed appropriate care. Cases of PL have been described in the literature, most commonly in association with congenital forms or in patients who exhibited symptoms since birth but were diagnosed later in life (5-7). Wright and Carty reported a case series of four children, aged 13 to 17 years, who presented with lower extremity edema (8). Each case posed a diagnostic challenge and was initially misattributed to endocrinological or rheumatologic disorders. However, following appropriate diagnostic radiologic evaluation, all were ultimately diagnosed with PL. This case series as well as our case demonstrates the importance for clinicians to maintain a high index of suspicion and keep a broad differential for children presenting with edema as the literature suggests that PL can be misdiagnosed leading to unnecessary treatments and delayed appropriate care.

Given the absence of a history suggestive of arthritis and the lack of supporting inflammatory and antibody laboratory findings, the initial diagnosis of JIA was erroneous. Lymphedema Is commonly misdiagnosed in children; literature estimates that approximately 1/4 of pediatric patients presenting with lower limb swelling are incorrectly labeled with this condition (2).

Although not applied to our patient during physical examination, the presence of Kaposi-Stemmer sign, indicated by the inability to pinch the fold of skin at the base of the second toe is considered pathognomonic (9). Imaging modalities should include radionuclide lymphoscintigraphy, which has high sensitivity and specificity, was instrumental in diagnosing our patient’s condition (10). While an MRI lacks both sensitivity and specificity, it can aid in excluding other causes of unilateral limb swelling. Additionally, evaluation of liver and kidney function can also help to rule out systemic causes of lower limb swelling (9). Another important consideration is the genetic testing, which may be indicated depending on family history. In our case, it was not pursued due to the absence of relevant familial findings, which was one of the limitations of this case report.

The goals of management in PL encompass reducing morbidity and enhancing overall functional outcomes. Our patient received CDT, the mainstay of therapy for PL, which incorporates manual lymphatic drainage, compression therapy, exercise, and skin care (9). Despite its intensive nature, CDT has demonstrated efficacy in improving swelling and overall quality of life (9,10). However, the case lacked a patient reported outcomes and had a relatively short follow up, which limits long-term assessment treatment efficacy and quality of life. Surgical interventions such as lymphovenous anastomosis (LVA) and vascularized lymph node transplantation (VLNT) have shown promising evidence and can be considered as options for treatment; however, they are reserved for refractory cases or significant anatomical disfigurement (11,12). Combined treatment with liposuction may be especially advantageous in the later stages of lymphedema, when fatty and fibrotic deposits are most prominent, and can help reduce limb circumference as well as infection risk (13,14).

Conclusions

Although PL is a rare diagnosis, this case highlights the importance of broadening the differential diagnosis and utilizing imaging in paediatric patients with unilateral lower limb swelling. Despite a negative rheumatologic evaluation and the absence of key clinical indicators supporting JIA, the patient underwent over a year of treatment with methotrexate. Early identification of diagnostic inconsistencies can help mitigate the risks associated with inappropriate therapy and facilitate timely further investigations.

Acknowledgments

We would like to express our gratitude to our patient and his family for recognizing the importance of sharing their clinical case, thereby contributing to the expansion of knowledge among healthcare providers.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://pm.amegroups.com/article/view/10.21037/pm-25-84/rc

Peer Review File: Available at https://pm.amegroups.com/article/view/10.21037/pm-25-84/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://pm.amegroups.com/article/view/10.21037/pm-25-84/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient’s legal guardians for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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