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Is NIVL pathogenic?

Ever since its first description, controversy has surrounded NIVL with regard to its pathologic import, because the lesion appears to be largely silent in the overwhelming majority of the population in which it is found. In fact, some have argued that the lesion be considered a ‘normal’ anatomical variant because of its quiescence and high prevalence.7 On the other hand, NIVL is undeniably causative of pathology in several subsets of patients. Cockett and colleagues highlighted NIVL as a cause of clinical acute iliac vein thrombosis.10 Hundreds of welldocumented cases of this type have appeared in the literature since. In a large registry11 of patients with acute iliac vein thromboses, NIVL-like lesions are detected in about one-third or more of patients after catheter-directed thrombolysis. Stent placement to correct such lesions after successful clot lysis is now standard practice. Cockett and colleagues also described a chronic form of disease caused by NIVL presenting with leg pain and swelling.3 They popularized the notion that this form of the disease was prone to affect the left lower limb of young women, even though their clinical series included older patients, men, and involvement of the right leg as well. The notion that NIVL is pathogenic at least in some patients is now readily accepted,12,13 but the relationship between the symptomatic lesions in patients and the asymptomatic ones in the general population has remained obscure.

NIVL as a permissive lesion
One way to reconcile these apparent contradictions is to view NIVL as a permissive lesion.9 A permissive lesion is one that is generally silent until an additional pathology or sequela is superimposed and triggers symptoms. Numerous permissive lesions are known to play a role in human pathology. A well-known example is patent foramen ovale, which has a population incidence similar to that of NIVL (20% to 30%), but remains silent except occasionally when passage of a paradoxical embolus takes place. Some other examples include gastroesophageal reflux disease and asthma, ureteric reflux and pyelonephritis, cricopharyngeal spasm and Zenker’s diverticulum, Helicobacter and peptic ulceration, obesity and diabetes, diabetes and neuropathy, middle lobe syndrome and pneumonia, carotid stenosis, and transient ischemic attacks. A general principle in treating many of these complex pathologies is to address the permissive lesion first, which alone may remit symptoms. In nonresponders, the secondary pathology may need to be addressed in sequence.
NIVL displays many of these characteristics of a permissive lesion. Despite its high incidence in the general population, it remains largely silent. We hypothesize that additional pathologies or sequelae such as trauma, cellulitis, distal thrombosis, lymphatic exhaustion, or reflux may render the extremity symptomatic. In the elderly, atherosclerosis of the overlying artery, venosclerosis, decreasing mobility, and leg dependency or other comorbid conditions predisposing to pedal edema may be contributory factors in symptom expression. In some cases no such secondary aggravating factors are apparent and symptom expression may simply be related to further progression of the stenotic lesion or to another as yet obscure cause.

2. Epidemiology: Venous stenoses are widely prevalent in the general population in silent form. A fraction become symptomatic when secondary insults are superimposed. The venous stenoses function in a “permissive” fashion. The incidence of the lesion in symptomatic patients therefore will be very high similar to the incidence of patent foramen ovale (a well-known permissive lesion) in patients with paradoxical embolus. Permissive lesions are ubiquitous in human pathology. Examples include obesity and diabetes, acid reflux and asthma, ureteral reflux and pyelonephritis to mention just a few examples. A general principle is to treat the permissive lesion first in symptomatic patients which is often curative; specific address of secondary trigger events will be required less frequently.