THORACIC SURGERY
Could thoracoscopic sympathicotomy for hyperhidrosis also improve acne vulgaris?

Introduction

Acne vulgaris is a common human skin disease, characterized by areas of skin with seborrhea, comedones, papules, pustules, nodules and possibly scarring. The classical aspects of multifactorial acne pathogenesis include abnormal follicular differentiation and increased cornification, androgen-mediated enhanced sebaceous gland activity and seborrhea, bacterial hyper-colonization, and inflammation [1]. It has been confirmed that facial skin from acne patients is characterized by increased numbers of substance-p containing nerves and mast cells, and by strong expression of neutral endopeptidase in sebaceous glands compared with normal skin [2]. The sebaceous gland expresses receptors for β-endorphin, corticotrophin-releasing factor, pro-opiomelanocortin, neuropeptide Y and calcitonin. Alpha-melanocyte stimulating hormone (α-MSH) has been evaluated not only as a sebotropin and pigmentation hormone but also as a modulator of inflammatory and immune tissue responses within the pilosebaceous unit [3, 4].
Primary hyperhidrosis is an idiopathic disorder characterized by excessive sweating. Its prevalence in the general population ranges from 0.3% to 4.5%. Video-assisted thoracoscopic sympathectomy (VATS) or sympathicotomy has been successfully applied for a long time in the treatment of hyperhidrosis [5].
The skin is innervated by sensory nerves and postganglionic sympathetic and parasympathetic fibers. In general, it is accepted that sebaceous glands are not innervated by the peripheral nervous system. On the contrary, it was shown that facial skin from acne patients showed numerous nerve fibers around and within sebaceous glands whereas in normal facial skin, nerve fibers were reported to be very rare [6].
During our follow-ups, we observed that after sympathectomy, the acne lesions of our patients subsided. The aim of this study is to evaluate the alterations of acne vulgaris grade in long-term follow-up of patients who have undergone thoracoscopic sympathicotomy for primary hyperhidrosis and to determine any correlation between acne vulgaris, clinical outcome and sympathicotomy.

Material and methods

Patients who had undergo thoracoscopic sympathicotomy for the treatment of facial/scalp primary hyperhidrosis or facial blushing in our unit were analyzed in a study design of retrospective review with prospective collection of the data from March 2005 to March 2013.
Data were collected on demographic details, operation, and complication. It was also recorded whether patients had acne vulgaris. The patients were evaluated for their acne severity and classified into 4 grades by dermatologists (Table I) before the surgery and at the follow-up.
The alteration in the severity of acne vulgaris before and after the operation was assessed using the Wilcoxon test. P < 0.05 was considered as statistically significant. All patients gave their informed consent before participating.

Results

Forty-two patients underwent thoracoscopic sympathicotomy for facial/scalp, hyperhidrosis or facial blushing between March 2005 and March 2013. All patients had undergone bilateral sympathicotomies. The 42 patients consisted of 18 females (42.85%) and 24 males (57.14%). The median age for females was 23 years and for males 25 years (Table II).
In 42 patients R2 sympathicotomy was done for facial/scalp hyperhidrosis or facial blushing. No patient experienced Horner syndrome, intercostal neuralgias or hemothorax perioperatively or in long-term follow-up. Two patients with facial hyperhidrosis still complain of having hyperhidrosis around their moustache after the surgery. None of the patients experienced a recurrence of hyperhidrosis or blushing at the follow-up.
All patients were advised preoperatively that long-term follow-up was necessary. Patients were contacted and assessed by return evaluation, telephone interviews, or questionnaires. Follow-up of the all patients ranged from 6 to 35 months (mean 19.3 ± 7 months).
Nine patients had developed new mild sweating in other areas after the operation but this does not bother the patients. New areas of increased sweating were most commonly described on the low back, abdomen, buttocks, and thighs. In 3 patients compensatory sweating occurred after 1 month following surgery, in 4 patients after 3 months following surgery, and in 2 patients within 2 years of surgery.
Thirty of these patients also had facial acne vulgaris. The patients with acne vulgaris were evaluated by dermatologists before and after the surgery. All 30 patients had undergone medical therapy for acne vulgaris in different medical centers for several years and stopped the treatment at a mean of 8 ± 2.4 months before the operation on their own decision due to no or minimal response to medical treatment. Twelve of these patients were female and 18 of them were male. Mean age was 18 years (range 14-24 years). Preoperative median acne grade was 2.5 (2-3) and after the operation at the follow-up, median acne grade was noted as 1 (0-1) (Table III and Figs. 1A-B). There was a statistically significant difference in the acne grade after the operation (p < 0.01).

Discussion

Primary hyperhidrosis presents most commonly in adolescents. It is a pathological condition of sweating in excess of that required for thermoregulation or psychological response with an unknown etiology. Excessive sweating usually affects the palms or axillae but may also affect other areas of the body [7]. Many reports have shown that thoracic sympathectomy for palmar hyperhidrosis is an efficient procedure, even after long-term follow-up periods [8, 9]. In this study there was no recurrence of hyperhidrosis after a follow-up period of 19.3 months.
Acne is a chronic disease which begins in the early teens with the onset of facial sebum production, and can persist in some cases into adulthood for unclear reasons. The pathogenesis of acne is multi-factorial, including hyperkeratinization of pilosebaceous ducts, enhanced sebaceous gland activity, bacterial hyperproliferation resulting in inflammation and an immunological reaction. Prevalence studies of acne by age showed an 85% prevalence rate in those aged 12-24 years [10]. Similarly, in our study mean age was 18 years. Postoperatively all 30 patients showed statistically significant improvement in their acne grade (p < 0.01).
The association between sympathectomy and acne was not reported before. However, Westphal et al. reported 2 patients, who had undergone bilateral VATS, who presented with hypopigmentation at the dermatomes corresponding to the sympathectomized regions [11]. The nervous system has an influence on skin (especially melanocytes which originate from neural crest cells) via neuropeptides; therefore a blockade on the sympathetic nerve stimulus through VATS might cause alterations in the epithelial melanocyte system. The skin can also locally produce adrenocorticotropin hormone (ACTH), melanocyte stimulating hormone (MSH), β-endorphin and corticotrophin-releasing hormone [12]. The alterations in the epithelial melanocyte system may affect α-MSH, which has modulatory effects via its receptor, melanocortin-1 receptor (MC1R). It was shown that epithelial cells of eccrine, apocrine and sebaceous glands also express MC1R [13]. Melanocortin-1 receptor immunoreactions were reported to be more accentuated in sebaceous glands of acne patients than healthy controls [14]. Additionally, an analogue of α-MSH (afamelanotide) was reported to be effective in the treatment of inflammatory acne recently [15].
In another hypothesis, another neurotransmitter hormone, melatonin (MT), might be the missing link between cutaneous and neural systems. Melatonin is synthesized by the pineal gland, and its production is suppressed by light (photoneuroendocrine control). The light generates an impulse, which is transferred to the pineal gland from the superior cervical ganglion via coronary nerves. In low light, the sympathetic system activates the synthesis of MT [16]. Melatonin is also synthesized and metabolized by keratinocytes. In contrast to the pineal gland, cutaneous MT exerts its effects in a receptor-dependent or independent way [17]. Melatonin receptor-1 (MT1R) was detected in eccrine sweat gland epithelial cells, whereas MT2R was present in eccrine sweat gland cells [12]. Interestingly, Maietta et al. concluded that possibly higher MT levels were related to seborrheic dermatitis pathology. The decrease in MT due to the blockade of the sympathetic system might cause a decrease in sebum synthesis which appears in acne pathogenesis [18].
In conclusion, we have observed that there is a significant improvement in the facial acne of patients who were sympathectomized for hyperhidrosis. Possibly, the neuroendocrine molecules have more interactions than known in skin biology. The decrease of acne lesions after sympathicotomy might be due to alterations of these molecules (α-MSH and MT). In order to better confirm this hypothesis, there is a need to design more detailed molecular prospective studies with an increased number of patients, investigating the effect of the nervous system on sebogenesis.

Disclosure

The authors report no conflict of interest.

References

1. Zouboulis CC, Eady A, Philpott M, Goldsmith LA, Orfanos CE, Cunliffe WC, Rosenfield R. What is the pathogenesis of acne? Exp Dermatol 2005; 14: 143-152.
I2. Toyoda M, Nakamura M, Makino T, Kagoura M, Morohashi M. Sebaceous gland in acne patients express high levels of neutral endopeptidase. Exp Dermatol 2002; 1: 241-247.
I3. Böhm M, Schiller M, Stander S, Seltmann H, Li Z, Brzoska T, Metze D, Schiöth HB, Skottner A, Seiffert K, Zouboulis CC, Luger Ta Metze D. Evidence for expression of melanocortin-1 receptor in human sebocytes in vitro and in situ. J Invest Dermatol 2002; 118: 533-539.
I4. Lipton JM, Catania A. Antiinflammatory actions of the neuroimmunomodulator α-MSH. Immunol Today 1997; 18: 140-145.
I5. Pilegaard HK. Thoracoscopic sympathectomy. J Clin Anal Med 2010; 1: 63-65.
I6. Toyoda M, Nakamura M, Morohashi M. Neuropeptides and sebaceous glands. Eur J Dermatol 2002; 12: 422-427.
I7. Byrne J, Walsh TN, Hederman WP. Endoscopic transthoracic electro-cautery of the sympathetic chain for palmar and axillary hyperhydrosis. Br J Surg 1990; 77: 1040-1049.
I8. Rex Lo, Drott C, Claes G, Gothberg G, Dalman P. The boras experience of endoscopic thoracic sympathicotomy for palmar, axillary, facial hyperhydrosis and facial blushing. Eur J Surg Suppl 1998; 580: 23-26.
I9. Lewis DR, Irvine CD, Smith FC, Lamont PM, Baird RN. Sympathetic skin response and patient satisfaction on long term follow-up after thoracic sympathectomy for hyperhidrosis. Eur J Vasc Endovasc Surg 1998; 15: 239-243.
I10. Chiu A, Chon SY, Kimball AB. The response of skin disease to stress: changes in the severity of acne vulgaris as affected by examination stress. Arch Dermatol 2003; 139: 897-900.
I11. Westphal FL, Campos JRM, Ribas J, Lima LC, Netto CL, Silva MS, Westphal DC. Skin depigmentation: could it be a complication caused by thoracic sympathectomy. Ann Thorac Surg 2009; 88: 42-43.
I12. Slominski A, Wortsman J, Tobin DJ. The cutaneous serotoninergic/melatoninergic system: securing a place under the sun. Faseb J 2005; 19: 176-194.
I13. Roosterman D, Goerge T, Schneider SW, Bunnett NW, Steinhoff M. Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiol Rev 2006; 86: 1309-1379.
I14. Ganceviciene R, Böhm M, Fimmel S, Zouboulis CC. The role of neuropeptides in the multifactorial pathogenesis of acne vulgaris. Dermatoendocrinol 2009; 1: 170-176.
I15. Böhm M, Ehrchen J, Luger TA. Beneficial effects of the melanocortin analogue Nle4-D-Phe7-α-MSH in acne vulgaris. J Eur Acad Dermatol Venereol 2014; 28: 108-111.
I16. Özçelik F, Erdem M, Bolu A, Gülsün M. Melatonin: general features and its role in psychiatric disorders. Current Approaches in Psychiatry 2013; 5: 179-203.
I17. Slominski A, Fischer TW, Zmijewski MA, Worstman J, Semak I, Zbytek B, Slominski MR, Tobin DJ. On the role of melatonin in skin physiology and pathology. Endocrine 2005; 27: 137-148. 18. Maietta G, Rongioletti F, Rebore A. Seborrheic dermatitis and daylight. Acta Derm Venereol 1991; 71: 538-539.