Introduction
Diagnosing facial and upper body oedema can be challenging because it requires a differential diagnosis that considers a range of conditions, such as angioedema, lymphatic oedema, endocrine disorders, and superior vena cava syndrome (SVCS). SVCS is an acute oncological condition that may be life-threatening, but it is often difficult to diagnose. The most common cause of SVCS is a disruption in blood flow through the superior vena cava or its main branches. This can occur due to external compression of the vessel or internal obstruction, such as a thrombus or a tumour mass. Lung cancer is the leading malignant cause of SVCS, accounting for 75–80% of cases [1]. Another significant factor, the role of which has significantly increased in the past two decades with the development of endovascular procedures, is thrombosis related to central venous catheters and pacemaker leads [2].
Aim
We present the case of a 60-year-old patient who was initially misdiagnosed and treated ineffectively for angioedema but was later diagnosed with superior vena cava syndrome. Through this case we aim to emphasise the importance of careful differential diagnosis in patients presenting facial and upper body oedema.
Case report
A 60-year-old female patient was admitted to the clinic due to progressively growing facial and upper-chest swelling, which had been present for approximately 3 weeks. During this period, the patient underwent multiple consultations with allergists and dermatologists, who suspected angioedema and prescribed a variety of antihistamines (fexofenadine 180 mg once daily, bilastine 20 mg twice daily, and cetirizine 10 mg twice daily) along with corticosteroids (prednisone 20 mg twice daily). However, rather than improving, the symptoms gradually worsened and additional complaints emerged, such as swelling of the arms, hoarseness, redness of the earlobes, telangiectasias on the skin of the chest, headaches, and dizziness (Figure 1).
As her symptoms continued to progress, the patient once again consulted a dermatologist, who suspected an allergic reaction and prescribed clemastine 1 mg once daily, along with topical treatments of methylprednisolone and panthenol. Despite this treatment, there was still no improvement, prompting her admission to hospital for further evaluation.
Upon admission to the clinic, the patient was in good general condition, with preserved verbal-logic contact, and she was haemodynamically and respiratorily stable. The patient’s medical history highlighted long-term nicotine use and a positive family history of cancer. On physical examination, the most notable findings were facial, head, neck, and upper chest oedema, scratch marks on the skin of the arms, and visible telangiectasias on the chest skin. Auscultation of the lung fields revealed scattered rhonchi on the right side.
Due to the suspicion of superior vena cava syndrome, a chest radiograph was performed, revealing a nodular opacity in the right side of the upper mediastinum and a possible partial atelectasis of the upper lobe of the right lung (Figure 2).
Subsequently, a computed tomography (CT) scan of the head, neck, and chest was conducted, which identified a nodular mass measuring 98 × 78 × 100 mm (anterior-posterior × cranio-caudal × latero-lateral), surrounding and infiltrating approximately 50% of the circumference of the right brachiocephalic trunk and about 80% of the initial segment of the right subclavian artery. The CT showed infiltration into the right brachiocephalic vein over a 62-mm segment with a slit-like lumen. The mass also involved 60% of the tracheal circumference over 67 mm, shifting it 10 mm left and causing mild stenosis. The examination also revealed several polycyclic, enlarged lymph nodes in the right supraclavicular region, consistent with metastatic involvement (Figures 3 A–D). Based on these findings, a diagnosis of superior vena cava syndrome was made, and systemic corticosteroids (dexamethasone 8 mg) and diuretics (furosemide 20 mg) were immediately initiated.
FIGURE 3
Computed tomographic (CT) images demonstrating a nodular opacity on the right side of the upper mediastinum (A, B – frontal plane, C – horizontal plane, D – horizontal plane angio-CT)
Two days later, the patient was transferred to the Department of Pulmonology for further diagnosis. Cytology of the material obtained from the 4R (right lower paratracheal) lymph node during bronchoscopy with endobronchial ultrasound (EBUS) revealed atypical cells, most likely consistent with small cell lung cancer. A computed tomography scan of the abdomen and pelvis showed no metastatic changes in the parenchymal organs. Due to the persistence of oedema despite symptomatic treatment, the first cycle of chemotherapy according to the EP (etoposide and cisplatin) regimen was implemented in the Oncology Department, which led to a gradual subsidence of the oedema.
Discussion
The diagnosis of SVCS is based on clinical presentation and imaging results. The initial diagnosis relies on the medical history and physical examination of the patient, which can be challenging to interpret due to the nonspecific nature of SVCS symptoms. In about one-third of patients, symptoms develop within 2 weeks, while in the remaining cases, they progress gradually [3]. Elevated venous pressure in the upper body leads to swelling of the head, neck, and arms, often accompanied by cyanosis and the expansion of subcutaneous veins [3]. Other symptoms, in order of frequency, include non-pulsatile enlargement of the jugular veins, chest vein dilation, dyspnoea and cough, arm swelling, hoarseness and/or stridor, loss of consciousness and/or headache, and altered mental status [4] (Table 1). Pleural effusions occur in 60% of patients with SVCS. They are usually small, occupying less than half of the chest cavity, and may be unilateral or bilateral. Most of these effusions are inflammatory or chylous in nature. While the aetiology of chylothorax appears to result from blocked flow due to increased hydrostatic pressure in SVCS and the left brachiocephalic vein, the pathogenesis of inflammatory effusions remains unknown. Potential causes of inflammatory effusions include factors such as diuresis, small pulmonary emboli, or underlying diseases – whether inflammatory or neoplastic – although their exact pathogenesis is not well understood. Effusion generally subsides with treatment of the SVCS obstruction [5].
TABLE 1
The incidence of the most common signs and symptoms of superior vena cava syndrome [3]
| Signs and symptoms | Incidence (%) |
|---|---|
| Facial oedema | 60–100 |
| Distended chest veins | 38–67 |
| Cough | 38–70 |
| Distended neck veins | 27–86 |
| Dyspnoea | 23–74 |
| Hoarseness | 15–20 |
| Arm oedema | 14–75 |
To develop the best treatment strategies for SVCS, a multidisciplinary approach involving clinical oncologists, surgeons, and interventional radiologists is essential. The severity of the patient’s condition and the need for rapid intervention depend on the degree of stenosis of the superior vena cava and the speed at which symptoms develop. As blood flow decreases, collateral circulation forms, allowing for a gradual reduction in pressure. In patients with rapidly progressing obstruction, symptoms are more pronounced because collateral vessels have not had time to develop [5]. In acute cases, the most commonly used imaging method for diagnosing SVCS and detecting its cause is contrast-enhanced computed tomography (CT), which has high sensitivity and specificity [6]. It allows for differentiation between thrombosis and external compression and helps identify collateral pathways [4]. Magnetic resonance imaging (MRI) is an acceptable alternative to CT for patients who have contraindications [3].
The standard treatment for SVCS includes chemotherapy with or without radiation therapy, surgical bypass, or endovascular interventions such as angioplasty, stenting, and thrombectomy using a catheter [4]. In life-threatening cases, initial patient stabilisation should involve elevating the head of the bed to reduce hydrostatic pressure in the head and neck, applying the ABC protocol (Airway, Breathing, Circulation), and then performing an endovascular procedure to alleviate symptoms [4]. For patients undergoing radiation therapy or those experiencing breathing difficulties, the additional use of corticosteroids and diuretics is recommended [6]. To assist in selecting the appropriate treatment, the grading system of the severity of SVCS based on the clinical presentation proposed by Yu et al. can be applied. Patients with mild symptoms (grade 1 and 2 or most of grade 3) should undergo further diagnostic workup to determine the type and stage of cancer. In cases with life-threatening symptoms (grade 4), immediate intervention is necessary, focusing on rapidly relieving the SVCS obstruction, preferably through endovascular stenting. An immediate treatment strategy is also recommended for cancers that are less responsive to radiochemotherapy, such as non-small cell lung cancer, and in situations with limited treatment options, such as mesothelioma [7] (Table 2).
TABLE 2
Proposed grading system for superior vena cava syndrome according to Yu et al. [7]
The presented case highlights the similarities between the symptoms of SVCS and angioedema, which may lead to an initial misdiagnosis. Many SVCS symptoms, such as neck and facial oedema, dyspnoea, and altered mental status, overlap with those of angioedema, complicating the correct diagnosis. SVCS may also be more challenging to diagnose due to the relatively high prevalence of angioedema, which affects approximately 1% of the global population at some point in their lives. Moreover, among patients with chronic spontaneous urticaria (CSU), around 10% experience angioedema without accompanying wheals, making the diagnosis even more difficult [8]. Through our research, we have encountered multiple case reports that illustrate the difficulties in distinguishing SVCS from angioedema, particularly when patients are on medications like ACE inhibitors or have been exposed to new substances. In the specific case reports we reviewed, the initial exposure to MRI contrast agents, diclofenac and henna, a commonly used colouring dye, were key factors that created a misleading clinical picture [9–14].
However, there are several distinctions that can aid in differentiating SVCS from angioedema, which should be considered. The difference between these conditions is often the episodic nature of angioedema symptoms, whereas SVCS symptoms are typically persistent and progressive over time. However, SVCS can present acutely, especially when caused by acute thrombogenesis on an endovascular catheter with concomitant lack of developed collateral circulation, which usually forms with a gradually increasing tumour mass [6]. On physical examination, enlarged neck and chest veins should suggest venous obstruction, especially if they worsen in the supine position, while urticaria should point to angioedema. It is also crucial to obtain a detailed patient history, including information of previous endovascular procedures, smoking, and family history of cancer. A positive allergic history may raise suspicion of angioedema. Additional clinical biomarkers can aid in identifying patients with chronic spontaneous urticaria. Elevated total IgE levels may indicate type I autoallergic CSU, while high IgG anti-TPO/total IgE ratios, along with basopenia and eosinopenia, are suggestive of type IIb autoimmune CSU [8].
Recurrent angioedema that does not respond to antihistamines, corticosteroids, epinephrine, or omalizumab requires additional exclusion of bradykinin-mediated angioedema. The cause of this condition is a deficiency of C1 inhibitor (C1-INH), which results in increased production of kinins that cause vasodilation and increased vascular permeability. C1-INH deficiency may be either inherited (HAE-C1INH), caused by pathogenic variants in the SERPING1 gene, or acquired (AAE-C1INH) due to the presence of neutralising antibodies against C1-INH in association with autoimmune or lymphoproliferative disorders [8, 15]. Hereditary C1-INH deficiency usually presents in childhood or adolescence, with recurrent, asymmetric episodes of cutaneous swelling that evolve gradually over several hours, last 2–5 days, and do not respond to glucocorticosteroids or antihistamines [15]. Attacks often involve the larynx and abdomen and may be preceded by prodromal symptoms such as erythema marginatum, whereas acquired forms typically present later in life and more commonly affect the face and oral mucosa [15, 16]. In the diagnostic process – particularly when differentiating from SVCS – it is important to consider a family history of recurrent angioedema, symptom exacerbation following trauma, and exposure to potential triggers such as angiotensin-converting enzyme (ACE) inhibitors or oestrogen, including during pregnancy or while using hormonal contraceptives [8, 16]. Laboratory tests typically show reduced levels of C4 and decreased levels and/or activity of C1-INH protein [17]. Testing should be repeated on a fresh blood sample after 1–3 months [15]. Reduced C1q levels are commonly observed in AAE-C1INH and help distinguish it from HAE-C1INH [15].
There are several other conditions that can present with subcutaneous oedema, which may initially resemble angioedema or SVCS. Among them, the presence of erythema, pruritus, and peeling of the skin after the oedema resolves, along with lack of response to antihistamines, may suggest contact dermatitis. A history of exposure to a new medication, combined with the appearance of polymorphic rashes, fever, eosinophilia, and involvement of the liver and kidneys, should raise suspicion for DRESS syndrome. Subcutaneous emphysema can also mimic angioedema but is distinguished by palpable crepitus over the swollen area, confirmed by chest X-ray or CT showing air in the subcutaneous tissue [18]. It should be suspected after trauma, pneumothorax, or surgical procedures, and typically spares the lips and tongue [19]. A critical cause is Boerhaave syndrome, which carries up to 40% mortality and may lack the full Mackler’s triad (vomiting, lower thoracic pain, and subcutaneous emphysema), making early recognition essential [20]. Another condition requiring differentiation is granulomatous cheilitis, especially in the context of Melkersson-Rosenthal syndrome, which additionally presents with a fissured tongue, swelling of the orofacial area, and facial nerve palsy. The list of conditions requiring differentiation from angioedema is long and additionally includes, among others, dermatomyositis, myxoedema in hypothyroidism, Morbihan’s disease, urticarial vasculitis with hypocomplementaemia, cluster headaches, and Gleichen’s syndrome [21].
Conclusions
Superior vena cava syndrome is a rare, usually late-onset complication of cancer, classified as an acute oncological emergency, which may present an immediate risk to the patient’s life. Despite extensive scientific research, diagnostic errors persist due to the non-specific nature of SVCS symptoms and their overlap with other conditions, such as angioedema. The case of our patient emphasises the importance of awareness of SVCS and the critical role of precise clinical evaluation to ensure proper patient management.
