Indian Journal of Dermatology
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Table of Contents 
CASE REPORT
Year : 2019  |  Volume : 64  |  Issue : 1  |  Page : 68-70
Systemic retinoids and scar dehiscence


1 Department of Plastic and Reconstructive Surgery, Bahcesehir University, Istanbul; Plastic, Reconstructive and Aesthetic Surgery Clinic, VM Medicalpark Kocaeli Hospital, Aksaray, Turkey
2 Department of Dermatology, Faculty of Medicine, Bahcesehir University, Istanbul; Dermatology Clinic, VM Medicalpark Kocaeli Hospital Kocaeli, Aksaray, Turkey
3 Department of Dermatology, Faculty of Medicine, Aksaray University, Aksaray, Turkey

Date of Web Publication7-Jan-2019

Correspondence Address:
Dr. Berna Aksoy
VM Medicalpark Kocaeli Hospital, Ovacik Discreet, Beside D-100 Highway, No: 36, Basiskele, Kocaeli
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: DOI: 10.4103/ijd.IJD_148_18

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   Abstract 


Systemic retinoids such as isotretinoin and acitretin are associated with numerous side effects but are therapeutically valuable in dermatological practice. Several studies have reported the wound-healing effects of treatment with concurrent systemic retinoids in addition to surgical treatments. Herein, we describe two patients with scar dehiscence that developed after initiation of systemic retinoid treatment following cutaneous surgery. In Case 1, isotretinoin was thought to decrease collagen production to a greater degree than did degradation during the wound remodeling phase, which resulted in wound dehiscence. In Case 2, acitretin was thought to decrease fibroblast proliferation and collagen production during the proliferation phase of wound healing, which resulted in wound dehiscence. Based on the two presented cases, it is advisable to postpone systemic retinoid treatment for 6 months to 1 year following cutaneous surgery, located especially in cosmetically important sites.


Keywords: Acitretin, dehiscence, isotretinoin, retinoid, scar, wound healing


How to cite this article:
Aksoy HM, Aksoy B, Çalikoglu E. Systemic retinoids and scar dehiscence. Indian J Dermatol 2019;64:68-70

How to cite this URL:
Aksoy HM, Aksoy B, Çalikoglu E. Systemic retinoids and scar dehiscence. Indian J Dermatol [serial online] 2019 [cited 2019 Jan 15];64:68-70. Available from: http://www.e-ijd.org/text.asp?2019/64/1/68/249531





   Introduction Top


Systemic retinoids such as isotretinoin and acitretin are essential for dermatological therapy but are associated with numerous side effects. Isotretinoin induces thinning of the skin.[1] It also decreases collagenase action and enhances hypertrophic or keloidal scarring following mechanical dermabrasion surgery and ablative laser treatment performed during, immediately after, and before isotretinoin treatment.[1],[2],[3] Findings in the literature concerning the adverse effects of systemic isotretinoin on wound healing are reported to be inconsistent.[1] Isotretinoin, when used in therapeutic dosages (≤2 mg/kg/d), does not seem to impair wound healing.[1] Moreover, the optimal timing for surgery in patients taking systemic isotretinoin remains unclear.[1] A comprehensive review of isotretinoin treatment and concurrent surgical procedures was inconclusive in this context.[2] Another consensus report concluded that there is insufficient evidence to recommend delaying cutaneous surgery not involving muscles in patients on isotretinoin treatment or in those who recently completed such treatment.[3] Another study reported that it is doubtful that isotretinoin can affect wound healing negatively, but there is a small risk that it may.[2] Surgical outcome in patients taking isotretinoin during the perioperative period was reported to be no different than in those not taking isotretinoin.[4] A study on organ transplant recipients undergoing surgical treatment for skin cancers reported there were no differences in wound-healing complications between those taking and not taking acitretin chemoprophylaxis;[5] however, only one study examined the outcome of previous surgical procedures during subsequent retinoid treatment.[6] Herein, we describe two cases of scar dehiscence that developed after initiation of systemic retinoid treatment following cutaneous surgery.


   Case Reports Top


Case 1

An otherwise healthy 17-year-old male undergone excision of an inflamed sebaceous cyst located on his right cheek. The patient presented again with nodulocystic acne and began treatment with oral isotretinoin 1 mg/kg/d. On day 29 of the treatment, he hit his right cheek and the incision scar (approximately 130 day old) was dehisced [Figure 1]. It was followed by local wound dressings while continuing oral isotretinoin treatment. The wound healed by secondary intention in about 2.5 months, leaving an atrophic depressed scar [Figure 2].
Figure 1: Scar dehiscence on the right cheek in Case 1 on day 29 of isotretinoin treatment

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Figure 2: In Case 1, the wound healed through secondary intention in about 2.5 months, leaving an atrophic scar on the right cheek

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Case 2

An 81-year-old male was operated for squamous cell carcinoma (SCC) located on the left ear helical border. A new tumoral nodule was detected on the right side of the midline of the forehead and excised 40 day later, and the histopathological diagnosis was again well-differentiated SCC. Oral acitretin 25 mg/d was initiated for chemoprevention of new SCC and treatment of widespread actinic keratoses. On day 8 of treatment, the surgical scar on the patient's forehead (25 day old) was dehisced. During the next few days, the left helical scar widened. Scar dehiscence on the forehead healed in about 7 weeks via secondary intention with wound dressings.


   Discussion Top


The literature includes only three patients reported to have developed complications of surgical procedures that occurred during or subsequent use of isotretinoin.[6] All three of these patients underwent septorhinoplasty before starting oral isotretinoin treatment in the previous 2 years and all developed nasal tip deformities within 6 months of the initiation of isotretinoin treatment. Authors concluded that nasal tip deformity had developed due to isotretinoin's creation of imbalance between collagen production and degradation, as well as the accentuated “shrink and wrap” phenomenon associated with the abnormally thin nasal epidermis, and recommended postponing isotretinoin treatment for a minimum of 2 years following rhinoplasty;[6] however, Cobo and Vitery[7] reported that concomitant initiation of isotretinoin treatment with rhinoplasty helped to define the nasal tip and improved the surgical outcome in thick-skinned patients.

Shigematsu and Tajima[8] reported that 13-cis-retinoic acid and etretinate inhibited collagen and noncollagenous protein synthesis in fibroblast cell cultures, although 13-cis-retinoic acid did so to a greater degree (66% reduction in collagen synthesis). Etretinate, but not 13-cis-retinoic acid, was reported to inhibit DNA synthesis (by 45%), and therefore, inhibited fibroblast proliferation; the researchers concluded that 13-cis-retinoic acid was the more valuable compound for the treatment of fibrotic disorders.[8] Ohta et al.[9] noted that all-trans-retinal (vitamin A aldehyde) (final collagenase activity was 14.3% of control) and all-trans-retinoic acid (final collagenase activity was 39.4% of control) were potent inhibitors of collagenase (MMP-1) production, but that 13-cis-retinoic acid (final collagenase activity was 57.7% of control) inhibited collagenase production to a lesser extent in human mononuclear cells in culture.

In Case 1, isotretinoin was thought to decrease collagen synthesis to a greater degree than collagen degradation during the postoperative wound remodeling phase. Due to this decrease in collagen synthesis, the patient's scar contained less collagen than normal scar at that age and was therefore weak, and dehiscence occurred following subsequent minor trauma. In Case 2, acitretin was started during the proliferation phase of wound healing. As acitretin inhibited both fibroblast proliferation and collagen synthesis, the patient's surgical wound was thought to get less cellular, with a decrease in collagen content and wound strength than normal scar at that age. Subsequently, the patient's scar dehisced spontaneously. The helical scar in Case 2 was older than that in Case 1 and was enlarged due to a decrease in collagen synthesis during the 3rd month of the wound remodeling phase. Since acitretin impaired collagen synthesis to a lesser degree in comparison with isotretinoin, it was thought that dehiscence was not observed in helical scar of Case 2. Acitretin was reported to delay secondary wound healing in rats.[10] Both of the presented cases experienced delayed secondary wound healing of dehisced scars while treatment with systemic retinoids was ongoing. Case 2 had an uneventful recovery following abdominal surgery and his third skin cancer excision.

Based on our experience with the presented cases, it is recommended that it may be beneficial to postpone systemic retinoid treatment for 6 months to 1 year following cutaneous surgery, located especially in cosmetically important sites. We concluded so because the remodeling phase of the wound healing process was generally completed in 1 year. Wound tensile strength is also related to this phase of wound healing and the maximum tensile strength of the wound is achieved in 3–6 months following creation of a wound.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgments

The authors would like to thank Scott Barry Evans for his assistance in native English language correction.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Ungarelli LF, Hetem CM, Farina Junior JA. Is it safe to operate on patients taking isotretinoin? Aesthetic Plast Surg 2016;40:139-48.  Back to cited text no. 1
    
2.
Wootton CI, Cartwright RP, Manning P, Williams HC. Should isotretinoin be stopped prior to surgery? A critically appraised topic. Br J Dermatol 2014;170:239-44.  Back to cited text no. 2
    
3.
Spring LK, Krakowski AC, Alam M, Bhatia A, Brauer J, Cohen J, et al. Isotretinoin and Timing of Procedural Interventions: A Systematic Review With Consensus Recommendations. JAMA Dermatol 2017;153:802-9.  Back to cited text no. 3
    
4.
Tolkachjov SN, Sahoo A, Patel NG, Lohse CM, Murray JA, Tollefson MM, et al. Surgical outcomes of patients on isotretinoin in the perioperative period: A single-center, retrospective analysis. J Am Acad Dermatol 2017;77:159-61.  Back to cited text no. 4
    
5.
Tan SR, Tope WD. Effect of acitretin on wound healing in organ transplant recipients. Dermatol Surg 2004;30:667-73.  Back to cited text no. 5
    
6.
Allen BC, Rhee JS. Complications associated with isotretinoin use after rhinoplasty. Aesthetic Plast Surg 2005;29:102-6.  Back to cited text no. 6
    
7.
Cobo R, Vitery L. Isotretinoin use in thick-skinned rhinoplasty patients. Facial Plast Surg 2016;32:656-61.  Back to cited text no. 7
    
8.
Shigematsu T, Tajima S. Modulation of collagen synthesis and cell proliferation by retinoids in human skin fibroblasts. J Dermatol Sci 1995;9:142-5.  Back to cited text no. 8
    
9.
Ohta A, Louie JS, Uitto J. Retinoid modulation of collagenase production by adherent human mononuclear cells in culture. Ann Rheum Dis 1987;46:357-62.  Back to cited text no. 9
    
10.
Gunes Bilgili S, Calka O, Akdeniz N, Bayram I, Metin A. The effects of retinoids on secondary wound healing: Biometrical and histopathological study in rats. J Dermatolog Treat 2013;24:283-9.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2]



 

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