Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Port wine stain (‘nevus flammeus’)
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Courtesy of Herbert Goodheart and Bob Rudolf
A port wine stain (PWS), also known as nevus flammeus , is a benign capillary malformation (CM) of the superficial cutaneous vasculature. These lesions are almost always congenital, though they may be acquired secondary to trauma and, thus, may rarely develop in adolescence or adulthood. The head and neck are sites of predilection, but any part of the integument can be affected. Morphologically, PWS present as light pink to red patches that typically grow proportionately with the child’s growth. Unlike the salmon patch (also known as nevus simplex or angel kiss ), which usually disappears during childhood untreated, PWS persist throughout a patient’s life and tend to darken with time. Confusing this clinical picture is that PWS may appear to lighten during the first 3–6 months of life, a physiologic change likely due to a decrease in blood hemoglobin concentration (typically 15–17 g/dL at birth to a nadir of 8–10 g/dL by 3 months of age) and should not be interpreted as a sign of clinical resolution. Skin thickening and development of surface irregularities (nodules or ‘blebs’) and soft tissue hypertrophy may occur, especially in the V2 distribution. PWS may also present with an inflammatory component consisting of scaling, excoriations, oozing, and crusting, which resembles an eczematous dermatitis.
In addition to being cosmetically distressing and its risk for long-term deformation, PWS may be associated with physical, social, and psychological sequelae. The presentation of a PWS on the face in the V1 distribution, for example, has been classically linked to the development of ocular and/or neurologic complications in the form of glaucoma or Sturge–Weber syndrome (SWS), especially with complete unilateral involvement of V1, bilateral involvement of V1, or a combination of V1, V2, and V3. Of note, anatomic variation in the distribution of V1 and V2 at the medial and lateral canthus (the so-called watershed areas ) has resulted in considerable difficulty in definitively defining distribution of a PWS occurring in these areas. Several papers have posited alternative methods of characterizing facial PWS and risk of SWS, highlighting segmental patterns that differ from traditional dermatomal designations. Two papers show that the distribution of facial PWS appears to follow the embryonic vasculature of the face instead of following the traditional delineation of the trigeminal nerve, with hemifacial (upper quarter and cheek involvement) and median (forehead) patterns representing the strongest predictor of SWS and possible later neural and ophthalmologic complications.
PWS may also be associated with overgrowth and complex vascular malformations (e.g., capillary–venous, capillary–venous–lymphatic, capillary–arteriovenous). Evaluation of non-facial PWS for limb overgrowth or evidence of complex malformations may warrant consideration of magnetic resonance imaging/magnetic resonance angiography (MRI/MRA) and/or referral to genetics or multidisciplinary vascular lesion clinics for diagnostic evaluation and management.
Although our understanding of the exact molecular pathogenesis of these CMs is evolving, it is believed that complex, localized defects in pathways controlling embryogenesis and angiogenesis play crucial roles. Whole genome sequencing of paired affected and normal tissue showed that GNAQ mutations are commonly associated with both SWS and non-syndromic PWS, as well as phakomatosis pigmentovascularis and diffuse CM with mild overgrowth. Evolving work has elucidated somatic mutations in other G proteins (e.g., GNA14 , GNA11 ), and the PTEN-PI3K-AKT-mTOR (e.g., PTEN , PIK3CA , AKT ) and RAS-RAF-MEK-ERK (e.g., NRAS , KRAS , RASA1 , MAP3K3 , MAP2K1 ) pathways. Many of these mutations are seen with PWS occurring concurrently with overgrowth syndromes, as well as PWS associated with arteriovenous malformations (e.g., RASA1 and EBHB4 mutations) and Parkes Weber syndrome. The potential for gene-directed therapy based on genetic targets is under investigation.
Management Strategy
Because of the well-recognized physical and psychosocial comorbidities associated with PWS, many specialists advocate for treatment as soon as possible after birth. Support for early intervention is based on the observation that early lesions are physically smaller in size and comprise smaller and more superficial vessels. Early treatment may improve responsiveness, decrease the overall number of treatments, and reduce the likelihood of long-term adverse outcomes.
Many therapeutic modalities have been utilized to treat PWS, including surgical excision and grafting, dermabrasion, cryotherapy, sclerotherapy, radium implants, X-ray therapy, electrocautery, tattooing, vascular-targeted photodynamic therapy and intense-pulsed light, and cosmetic camouflage.
Various lasers have been used, including CO 2 , neodymium:yttrium-aluminum-garnet (Nd:YAG), argon, and copper vapor lasers, but results have been unsatisfactory, with the risk of scarring unacceptably high. Consequently, the flashlamp-pumped pulsed dye laser (PDL) is considered by most authorities to be the gold standard of treatment for PWS. Treatment settings should be based on therapeutic end points, e.g., purpura. More recently, dynamic optical coherence tomography and in vivo reflectance confocal microscopy have been used to provide quantitative visualization and guidance for tailored laser treatment protocols, but these techniques remain experimental. Lightening and/or reduction in size of the stain is directly related to the number of treatments. Initial treatments usually give the highest percentage of improvement. Generally, the smaller, more superficial vessels are targeted with the PDL, and deeper, larger-caliber vessels may require longer pulse durations or longer wavelength lasers. Other modalities have been used for refractory PWS, including long-pulsed alexandrite and Nd:YAG lasers, intense-pulsed light, and photodynamic therapy.
Swelling, erythema, and pain are frequently present immediately after treatment with PDL. Other potential adverse events include postinflammatory dyspigmentation (especially in darker-skinned patients), immediate postlaser purpura, and recurrence of the lesion itself. Rarely, blistering, crusting, scarring, and infection may occur. For these reasons, a test area may be performed before a full treatment session. Sun exposure can drastically affect pigmentary changes, and sun avoidance/protection should be optimized prior to and between treatment sessions. Before and after photos are a helpful tool for demonstrating clinical efficacy and for assuaging patient and family fears.
Cooling the skin via an attached device utilizing a targeted cryogenic spray or by application of a cool air machine is crucial to minimizing damage to surrounding tissues and reducing the risk of postoperative complications. Cold compresses and/or bags of ice applied immediately to the treated area are also useful for preventing postoperative complications.
Measures to overcome pain and anxiety associated with laser use include topical anesthetics such as lidocaine 4% gel, eutectic mixture of 2.5% lidocaine and 2.5% prilocaine, local lidocaine infiltration, cold air chiller devices, nerve block, sedation, and general anesthesia. Concerns about general anesthesia and potential neurotoxic effects in young children have been raised and should be considered in discussions about approaches to therapy, though not negating the utility and effectiveness of early laser therapy.
Topical daily treatment with 1% rapamycin cream after laser treatment may improve responsiveness to laser therapy through an unknown mechanism, possibly by decreasing vascular proliferation through the mTOR and HIF-1α pathway.
Specific Investigations
|
|
|
Facial port wine stains and Sturge–Weber syndrome
Enjolras O, Riche MC, Merland JJ. Pediatrics 1985; 76: 48 – 51.
SWS was present in 28.5% of patients with PWS covering the V1 trigeminal sensory area alone or in association with V2 and V3, and 9.5% had glaucoma.
Sturge–Weber syndrome in patients with facial port-wine stain
Piram M, Lorette G, Sirinelli D, et al. Pediatr Dermatol 2012; 29: 32 – 7.
This cross-sectional study of 259 patients with facial PWS included 15 patients with a diagnosis of SWS. All patients with SWS showed involvement of the V1 trigeminal cutaneous area. SWS was significantly associated with bilateral topography of the PWS, its extension to another territory, and involvement of the upper eyelid.
This study provides valuable data to support risk stratification of a facial PWS for SWS and glaucoma based on anatomic distribution.
Facial port-wine stain: when to worry?
Melancon JM, Dohil MA, Eichenfield LF. Pediatr Dermatol 2012; 29: 131 – 3.
A ‘comment’ on the aforementioned article by Piram et al. discussing the anatomic variations that have made direct comparison of the available literature difficult and providing insight in terms of management.
Location of port-wine stains and the likelihood of ophthalmic and/or central nervous system complications
Tallman B, Tan OT, Morelli JG, et al. Pediatrics 1991; 87: 323 – 7.
Among patients with trigeminal PWS, 8% had evidence of eye and/or CNS involvement. PWS of the eyelids, bilateral distribution, and unilateral PWS involving all three branches of the trigeminal nerve were associated with a significantly higher likelihood of having eye and/or CNS complications.
Patients with such presentations should be screened for glaucoma, and the risk of CNS involvement should be discussed with the family and appropriate testing considered.
New vascular classification of port-wine stains: improving prediction of Sturge-Weber risk
Waelchli R, Aylett SE, Robinson K, et al. Br J Dermatol 2014; 171: 861 – 7.
Of 192 children with facial PWS seen in 2011 to 2013, PWS involving any part of the forehead, which corresponds well to the embryonic vascular development of the face, was the best predictor of adverse outcomes.
Children with PWS on any part of the forehead should undergo ophthalmologic evaluation and brain MRI.
A prospective study of risk for Sturge-Weber syndrome in children with upper facial port-wine stain
Dutkiewicz AS, Ezzedine K, Mazereeuw-Hautier J, et al. J Am Acad Dermatol 2015; 72: 473 – 80.
In this prospective multicenter study of 66 patients, 11 presented with SWS and four had suspected SWS without neurologic manifestations. These patients predominantly had hemifacial or median PWS patterns that were high risk for SWS.
Hemifacial or median PWS patterns conform to areas of somatic mosaicism and are high risk for SWS.
Sturge–Weber syndrome and dermatomal facial port-wine stains: incidence, association with glaucoma, and pulsed tunable dye laser treatment effectiveness
Hennedige AA, Quaba AA, Al-Nikib K. Plast Reconstruct Surg 2008; 121: 1173–80.
In this study of 874 patients, SWS occurred in 3% of all patients with facial PWS and 10% of those whose PWS were in a dermatomal distribution. Although both SWS and glaucoma occurred in patients with only V1 involvement, the risk increased substantially with V1 + V2 and V1 + V2 + V3 involvement. No patients with only V3 involvement had eye or CNS findings.
Children at risk of SWS should have ophthalmologic examination in the neonatal period and require ophthalmologic follow-up because glaucoma may develop subsequent to initial presentation.
Size of facial port-wine birthmark may predict neurologic outcome in Sturge-Weber syndrome
Dymerska M, Kirkorian AY, Offermann EA, et al. J Pediatr 2017; 188: 205–9.
The size of the port wine birthmark in Sturge–Weber syndrome predicts neurologic severity of disease.
Retrospective review of screening for Sturge-Weber syndrome with brain magnetic resonance imaging and electroencephalography in infants with high-risk port-wine stains
Zallmann M, Mackay MT, Leventer RJ, et al. Pediatr Dermatol 2018; 35(5): 575–81.
Children with PWS with positive screening MRI will almost certainly develop Sturge–Weber syndrome. Negative-screening MRI cannot exclude Sturge–Weber syndrome (in up to 23.1% of cases).
Analyzing the genetic spectrum of vascular anomalies with overgrowth via cancer genomics
Siegel DH, Cottrell CE, Streicher JL, et al. J Invest Dermatol 2018; 138(4): 957–67.
The authors assembled a 16-institution network to determine the genetic variants associated with the spectrum of vascular anomalies with overgrowth. Using tumor genetic profiling via next-generation sequencing, the authors found that most vascular anomalies with overgrowth harbor postzygotic gain-of-function mutations in oncogenes. Seventy-five percent of subjects harbored pathogenic or likely pathogenic variants in 10 genes, many of which contained variants previously described in cancer settings and not described in vascular malformations. The authors conclude that this methodology can be applied to study other benign developmental disorders that may also contain gain-of-function mutations in oncogenes.
Anatomic differences of port-wine stains in response to treatment with pulsed dye laser
Renfro L, Geronemus RG. Arch Dermatol 1993; 129: 182–8.
Centrofacial lesions and lesions involving dermatome V2 responded less favorably than lesions located elsewhere on the head and neck.
Facial port wine stains in childhood: prediction of the rate of improvement as a function of the age of the patient, size and location of the port wine stain and the number of treatments with the pulsed dye (585 nm) laser
Nguyen CM, Yohn JJ, Huff C, et al. Br J Dermatol 1998; 138: 821–5.
Major determinants of treatment response, in order of decreasing importance, are PWS location, size, and patient age. The most successful responses are seen in young patients (under 1 year of age) with small PWS (<20 cm 2 ) located over bony areas of the face, such as the central forehead. The greatest percentage of size reduction occurred after the first five treatments. There was less reduction in size with subsequent treatments.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here
