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ORIGINAL CONTRIBUTIONS

Received: April 24^th 2015

Accepted: July 13^rd 2015

Verapamil in conjunction with pressure therapy in the treatment of pathologic scar due burn injury

Guillermo Ramos-Gallardo,^a Ariel Miranda-Altamirano,^a Rebeca Valdes-López,^a Sandra Figueroa-Jiménez,^a Leonel García-Benavides^a

^aUnidad de Atención al Niño Quemado, Nuevo Nuevo Hospital Civil de Guadalajara “Juan I. Menchaca”, Guadalajara, Jalisco, México

Communication with: Guillermo Ramos-Gallardo

Telephone: (33) 3632 1077

Email: guiyermoramos@hotmail.com

Background: Keloids and hypertrophic scars are dermal fibro-proliferative disorders unique to humans. Their treatment is a true challenge with multiple options, but not all the time with good results. Unfortunately this problem is not uncommon in patients with history of burn injury. The aim of this article is to evaluate the use of verapamil and pressure garments in patients with hypertrophic or keloid scar caused by burn injury.

Methods: We included patients with a hypertrophic or keloid scar caused by burn injury candidate to treatment with pressure garment. The pathologic scars were evaluated by serial photographic records, Vancouver and Posas scales. The scales of Vancouver and Posas were compared with t Student.

Results: We included 13 scars in 11 patients. Four scars were located in the legs, 4 in the arms, 4 in the face-neck and 1 in the abdomen. The dose of verapamil was calculated .03mg per kg. Injections were scheduled every 7 to 10 days until complete 6 sessions. Taking in count Posas scale, patients referred improvement in pigmentation (.01), thickness (.005), flexibility (.01) and surface area (.004). In the Vancouver scale the observers mentioned improvement in elevation (.008), pigmentation (.014), vascularity (.022), flexibility (.014) and pruritus (.003). No adverse effects were found in verapamil injection.

Conclusions: Verapamil was useful in conjunction with pressure garment to improve the condition of the keloid and hypertrophic scar caused by burn.

Keywords: Keloid; Burns; Verapamil; Hypertrophic cicatrix

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The pathological process including hypertrophic or keloid scars are a difficult problem to manage in patients with a history of burns. Large areas are affected causing limitation in motion and function. A useful treatment option is pressure therapy, especially with garments, tools widely used in North America and Europe.^1-3 Patients with burn sequelae must have follow-up from a multidisciplinary team with many specialists involved in order to begin rehabilitation and identify any limitations in function or movement.

Unfortunately, during the process of scar maturation, in addition to the various measures and efforts, the problem continues to limit the quality of life in these patients.^2,3 We propose using intralesional verapamil in combination with pressure therapy and garments. Since verapamil has proven a useful tool in the treatment of pathological scarring, the literature has reported changes in the form of fibroblasts and decreased interleukin 6 and other markers.^4-6 There are no reports in the Mexican population about this drug in patients with impaired healing from burn sequelae.

Methods

We did a prospective study in patients with keloid or hypertrophic scarring from January 2014 to June 2014.

It included patients with a newly-diagnosed burn injury (less than 12 months) with scarring (hypertrophic or keloid) who were candidates for management with pressure garments.

The research project was approved by the Ethics Committee of the Nuevo Hospital Civil de Guadalajara “Juan I. Menchaca" (number: 1376-1314).

The cases were documented with images of the pathological scarring (hypertrophic or keloid) before and at the end of treatment. Posas and Vancouver scales were assessed before and after treatment. Intralesional verapamil was injected as additional treatment for the scarring. The medication was administered every 7 to 10 days for 6 sessions. Doses were calculated on the basis of 0.03 mg per kg. Results of Posas and Vancouver scales were compared with Student’s t-test.

Results

126 patients with a recent history of burn injuries were evaluated over six months from January 2014 to June 2014. 45 of these patients (35%) were candidates for pressure therapy (garments under the trade name Cicamed). Of these we included 11 patients (8.5%) who accepted, they and their parents, to participate in the study. The garments provided pressure on the scars of 25 mm/Hg. Intralesional verapamil was administered in 13 scars.

Table I shows the patient, location, and type of scar evaluated. Figure 1 shows an example of the scar on the face and neck, before and after treatment with verapamil.

The drug was administered every 7 to 10 days for 6 sessions. We observed no side or secondary effects with drug administration.

Tables II and III show the results of Vancouver and Posas scales comparing before and after treatment.

Discussion

The early use of pressure garments is recommended routinely in different centers around the world; although it is not detrimental to patients, reports and tests show different results. Pressure therapy was first popularized by the Shriners Burn Hospital in Galveston. In 1971, Larson, of the same group, reported that pressure therapy decreased hypertrophic scarring after thermal injury,¹ many reports were followed without evidence of controlled studies. In recent years there have been different studies, the results of which tend to vary among each other. Anzarut et al. in 2009 published a meta-analysis of different trials reporting the use of pressure garments, and concluded that there is insufficient evidence to support their routine use.²

Pressure garments can improve the maturation process by restricting blood flow to the scar area, and the constant compression that inhibits the growth of hypertrophic tissue. Pressure facilitates control of collagen synthesis by reducing blood supply, oxygen, and nutrients, which can be noticed from the reduced redness of the scar and edema.^1,2

Engrav and his group, in Seattle, did a well-designed study where they propose a rational use of pressure garments. The scar size, location, and degree of burn depth were analyzed. They presented a retrospective study over 12 years with one year of follow-up including 54 patients. They concluded that the benefit of this therapy may be suggested in deep second-degree burn scars, third-degree burns with skin grafts, scars that have healed spontaneously within several weeks, children and young adults, people of color, and body locations where pressure can be applied.³

In our center, as in many centers around the world, different specialists are involved in monitoring patients. Early movement and physical therapy is promoted. Ultrasound and electrical stimulation are used routinely when the location of the scar permits.

The psychology department evaluates each patient and proposes treatment according to different factors, where the perception of the scar and function are the main focus. Family support is important in the care of our patients, in order to have good treatment compliance; especially in the case of pressure therapy, because of the age of our patients, it becomes difficult to follow the instructions without parental help. Despite our efforts, in some cases improvement of scars is not found, which affects the quality of life of our patients.

Considering recent evidence with the use of verapamil, we proposed early use of this drug; we are also convinced that pressure therapy is a useful tool in the treatment of scarring after a burn injury.

Verapamil has different benefits on keloid fibroblast growth. There are reports showing the effect on interleukin 6 (IL-6) and the secretion of vascular endothelial growth factor and cell growth in primary culture of fibroblasts derived from the central part of the keloid.^5,6 It also has an effect in modulating collagen biosynthesis, changes the morphology of fibroblasts, and the reorganization of actin filaments, as revealed by staining with fluorescein isothiocyanate FITC in microscopy.^7,8

Verapamil, alone or in combination with surgery, has shown efficacy in the treatment of keloid scarring.^9,10

Studies have recently reported comparing verapamil and triamcinolone. Margaret Shanti and Ernest Dhanraj reported a randomized, single-blind study that included 54 patients, finding reduced scar vascularization, flexibility, height, and width after 3 weeks of treatment. However, the result was faster in the triamcinolone group; however, more adverse effects were found with this group, such as skin fragility and hypochromy.¹¹

In another study also conducted in India, Rajeev B. Ahuja and Pallab Chartterjee compared the use of verapamil and triamcinolone in hypertrophic and keloid scars. They showed the effects of both drugs in a randomized blind study. Forty patients were included. Triamcinolone was used in 22 scars and verapamil in 26. They found improvement in scar vascularity, flexibility, and height. They proposed the use of verapamil because the cost is lower, as are the side effects.¹² In this study drugs were administered every three weeks, the advantage of verapamil being that it can be administered every 7 to 10 weeks, giving the option to finish the treatment schedule in less time.

We know that more well-designed studies are needed to answer questions such as those concerning dosage and possible side effects, which is probably a major weakness of our report; however, we are conducting a randomized study that can help clarify these questions. Most evidence shows benefit with verapamil, however, the size of the scar treated was not as big.¹³ With this report we propose the use of verapamil to aid treatment adherence with pressure garments with pathological scarring caused by burns in which no improvement is initially observed.

Conclusions

Verapamil in combination with pressure therapy improves Posas and Vancouver scales in pathological scarring (keloid and hypertrophic scar) with a history of burn injuries. Our patients and their relatives (parents) reported improvement in pruritus, pigmentation, thickness, and flexibility. We also observed improvement in pigmentation, flexibility, vascularization, and scar height. More studies are needed to determine the ideal dose of this medication in the treatment of pathological scars in patients with burns.

References

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3. Engrav L.H., Heimbach D.M., Rivara F.P. 12 years within wound study of the effectiveness of custom pressure garment therapy. Burns 2010;36:975-983.
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6. Doong H, Dissanayake S, Gowrishankar TR. Calcium antagonist alter cell shape and induce procollagenase synthesis in keloid and normal human dermal fibroblasts. J Burn Care Rehabil 1996;17 (6pt 1):497-514.
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9. D´Andrea F, Brongo S, Ferraro G, Baroni A. Prevention and treatment of keloids with intralesional verapamil. Dermatology 2002;204(1):60-62.
10. Lawrence, W. T. Treatment of earlobe keloids with surgery plus, adjuvant intralesional verapamil and pressure earrings. Ann. Plast. Surg. 37:167,1996.
11. Ahuja RB, Chatterje P. Comparative efficacy of intralesional verapamil hydrochloride and triamcinolone acetonide in hypertrophic scars and keloids. Burns 2014;40:583-588.
12. Shanti M, Dhanrah P. Comparison of intralesional verapamil with intralesional triamcinolone in the treatment of hypertrophic scars and keloids. Indian J Dermatol Venereol Leprol 2008;74(4):343-348.
13. Ledon JA, Savas J, Franca K. Intralesional treatment for keloids and hypertrophic scars: a review. Dermatol Surg 2013;39(12):1745-1757.

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