- Email: [email protected]
Nicorandil-associated penile and anal ulceration triggered by circumcision
British Journal of Medical and Surgical Urology (2010) 3, 175—177
CASE REPORT
Nicorandil-associated penile and anal ulceration triggered by circumcision Sai Yee Chuah a,∗, Derek J. Byrne b, Sharon Edwards c, Andrew Affleck a a
Department of Dermatology and Photobiology, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom b Urology Department, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom c Histopathology Department, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom Received 22 September 2009; accepted 12 October 2009
KEYWORDS Nicorandil; Penile and anal ulceration; Circumcision
Case history A 72-year-old man was referred to Dermatology by Urology with a 5-month history of non-healing painful penile ulcer arising after circumcision for recurrent non-specific balantitis associated with phimosis. The patient felt that ‘it had never quite healed properly’. Three months after the circumcision, extensive ulceration developed on the shaft and base of penis and clinically similar deep ulceration then arose on his right buttock perianally. Relevant medical history included ischaemic heart disease, previous myocardial infarction, atrial fibrillation, Type 2 diabetes mellitus and diverticular disease. Regular medications were ∗ Corresponding author. Tel.: +44 1382 660111; fax: +44 1382 646047. E-mail addresses: [email protected] (S.Y. Chuah), [email protected] (D.J. Byrne), [email protected] (S. Edwards), andrew.affl[email protected] (A. Affleck).
Nicorandil, Bisoprolol, Simvastatin, Warfarin, Allopurinol, Omeprazole, Metformin, Tramadol and GTN spray. These were all long-standing and unchanged. Physical examination revealed an extensive deep ulcer at the base of the penis and confluent erosion over the shaft and several deep perianal ulcers (Fig. 1). There was no inguinal lymphadenopathy. Bacterial and viral swabs were negative. A skin biopsy was non-specific showing epidermal ulceration, inflamed granulation tissue and fibrosis (Fig. 2). The superficial variant of pyoderma gangrenosum could not be excluded histologically but the clinico-pathological picture was highly suggestive of nicorandil-induced penile and perianal ulceration as previously reported and so this drug, which the patient had been taking since June 2002 for angina prophylaxis at a dose of 30 mg bd, was discontinued. He was also treated with super-potent topical steroid (Dermovate® cream) once daily, Aquacel
1875-9742/$ — see front matter © 2009 British Association of Urological Surgeons. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.bjmsu.2009.10.001
176
S.Y. Chuah et al.
Figure 3 Healing of both ulcerated areas 4 months after discontinuation of nicorandil. Figure 1 Extensive ulceration of penis and perianal region.
dressing and oral Clarithromycin XL 500 mg od to gain maximum symptomatic relief and as prophylaxis for possible secondary bacterial infection. There was considerable improvement over 4 weeks although complete healing of both ulcerated areas took almost 4 months after cessation of Nicorandil (Fig. 3).
Discussion Nicorandil is a vasodilator with a dual mechanism of action. It opens up ATP-sensitive K+ channels, thereby causing dilatation of peripheral and coronary resistant arterioles. It also has a nitrate moiety which dilates systemic veins and epicardial coronary arteries [1].
Reports of gastrointestinal ulcers of the mouth, perianal region, small intestine, colon and even stomas associated with nicorandil have been made in the literature [2]. Cutaneous ulcers of the leg and chest skin associated with pacemaker site insertion have recently been reported [3]. Only two cases of penile ulcers associated with nicorandil have been reported one of which may have been triggered by trauma from a trouser zip fastener [4,5]. In our case, it appeared that circumcision may have been the precipitating factor of the non-healing penile ulcer. Interestingly, perianal ulceration was also noted to arise one month thereafter. The mechanism of action involving nicorandilinduced ulceration has been postulated to be related to a NAD/NADP and nicotinic aciddependent effect [1]. Cessation of the nicorandil usually results in resolution of ulcer whilst other interventions are usually ineffective. In conclusion, we have highlighted a case of nicorandil-associated penile and anal ulceration which appears to have been triggered by circumcision. A history of nicorandil intake should always be enquired about in the diagnosis of a nonhealing ulcer after urological surgery to avoid costly investigations and therapeutic interventions. In retrospect, if the association of nicorandil and penile ulceration had been recognised, this may have prevented the progression and worsening of the ulcers and hence, reduced the morbidity of our patient.
Conflict of interest statement Figure 2 Epidermal ulceration with inflamed granulation tissue (haematoxylin and eosin; original magnification 100×).
The authors declare that there are no conflicts of interest.
Nicorandil-associated penile and anal ulceration triggered by circumcision
References [1] Trechot P, Barbaud A, Petitpain N, Claeys A, Schmutz JL. Nicorandil and ulcerations: a NAD/NADP and nicotinic aciddependent side-effect? Br J Dermatol 2008;158:1150—1. [2] Toquero L, Briggs CD, Bassuini MM, Rochester JR. Anal ulceration associated with Nicorandil: case series and review of the literature. Colorectal Dis 2006;8:717—20.
177
[3] Jennesseaux I, Carre-Gislard D, Bravard P. Nicorandilinduced cutaneous ulceration on a pacemaker implantation wound. Ann Dermatol Venereol 2008;135:131—3. [4] Bhatti I, Cohen SN, Bleiker T, Lund J, Tierney G. Nicorandilinduced foreskin ulceration. Colorectal Dis 2009;11:424—5. [5] Birnie A, Dearing N, Littlewood S, Carlin E. Nicorandilinduced ulceration of the penis. Clin Exp Dermatol 2008;33:215—6.
Available online at www.sciencedirect.com
CASE REPORT
Nicorandil-associated penile and anal ulceration triggered by circumcision Sai Yee Chuah a,∗, Derek J. Byrne b, Sharon Edwards c, Andrew Affleck a a
Department of Dermatology and Photobiology, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom b Urology Department, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom c Histopathology Department, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom Received 22 September 2009; accepted 12 October 2009
KEYWORDS Nicorandil; Penile and anal ulceration; Circumcision
Case history A 72-year-old man was referred to Dermatology by Urology with a 5-month history of non-healing painful penile ulcer arising after circumcision for recurrent non-specific balantitis associated with phimosis. The patient felt that ‘it had never quite healed properly’. Three months after the circumcision, extensive ulceration developed on the shaft and base of penis and clinically similar deep ulceration then arose on his right buttock perianally. Relevant medical history included ischaemic heart disease, previous myocardial infarction, atrial fibrillation, Type 2 diabetes mellitus and diverticular disease. Regular medications were ∗ Corresponding author. Tel.: +44 1382 660111; fax: +44 1382 646047. E-mail addresses: [email protected] (S.Y. Chuah), [email protected] (D.J. Byrne), [email protected] (S. Edwards), andrew.affl[email protected] (A. Affleck).
Nicorandil, Bisoprolol, Simvastatin, Warfarin, Allopurinol, Omeprazole, Metformin, Tramadol and GTN spray. These were all long-standing and unchanged. Physical examination revealed an extensive deep ulcer at the base of the penis and confluent erosion over the shaft and several deep perianal ulcers (Fig. 1). There was no inguinal lymphadenopathy. Bacterial and viral swabs were negative. A skin biopsy was non-specific showing epidermal ulceration, inflamed granulation tissue and fibrosis (Fig. 2). The superficial variant of pyoderma gangrenosum could not be excluded histologically but the clinico-pathological picture was highly suggestive of nicorandil-induced penile and perianal ulceration as previously reported and so this drug, which the patient had been taking since June 2002 for angina prophylaxis at a dose of 30 mg bd, was discontinued. He was also treated with super-potent topical steroid (Dermovate® cream) once daily, Aquacel
1875-9742/$ — see front matter © 2009 British Association of Urological Surgeons. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.bjmsu.2009.10.001
176
S.Y. Chuah et al.
Figure 3 Healing of both ulcerated areas 4 months after discontinuation of nicorandil. Figure 1 Extensive ulceration of penis and perianal region.
dressing and oral Clarithromycin XL 500 mg od to gain maximum symptomatic relief and as prophylaxis for possible secondary bacterial infection. There was considerable improvement over 4 weeks although complete healing of both ulcerated areas took almost 4 months after cessation of Nicorandil (Fig. 3).
Discussion Nicorandil is a vasodilator with a dual mechanism of action. It opens up ATP-sensitive K+ channels, thereby causing dilatation of peripheral and coronary resistant arterioles. It also has a nitrate moiety which dilates systemic veins and epicardial coronary arteries [1].
Reports of gastrointestinal ulcers of the mouth, perianal region, small intestine, colon and even stomas associated with nicorandil have been made in the literature [2]. Cutaneous ulcers of the leg and chest skin associated with pacemaker site insertion have recently been reported [3]. Only two cases of penile ulcers associated with nicorandil have been reported one of which may have been triggered by trauma from a trouser zip fastener [4,5]. In our case, it appeared that circumcision may have been the precipitating factor of the non-healing penile ulcer. Interestingly, perianal ulceration was also noted to arise one month thereafter. The mechanism of action involving nicorandilinduced ulceration has been postulated to be related to a NAD/NADP and nicotinic aciddependent effect [1]. Cessation of the nicorandil usually results in resolution of ulcer whilst other interventions are usually ineffective. In conclusion, we have highlighted a case of nicorandil-associated penile and anal ulceration which appears to have been triggered by circumcision. A history of nicorandil intake should always be enquired about in the diagnosis of a nonhealing ulcer after urological surgery to avoid costly investigations and therapeutic interventions. In retrospect, if the association of nicorandil and penile ulceration had been recognised, this may have prevented the progression and worsening of the ulcers and hence, reduced the morbidity of our patient.
Conflict of interest statement Figure 2 Epidermal ulceration with inflamed granulation tissue (haematoxylin and eosin; original magnification 100×).
The authors declare that there are no conflicts of interest.
Nicorandil-associated penile and anal ulceration triggered by circumcision
References [1] Trechot P, Barbaud A, Petitpain N, Claeys A, Schmutz JL. Nicorandil and ulcerations: a NAD/NADP and nicotinic aciddependent side-effect? Br J Dermatol 2008;158:1150—1. [2] Toquero L, Briggs CD, Bassuini MM, Rochester JR. Anal ulceration associated with Nicorandil: case series and review of the literature. Colorectal Dis 2006;8:717—20.
177
[3] Jennesseaux I, Carre-Gislard D, Bravard P. Nicorandilinduced cutaneous ulceration on a pacemaker implantation wound. Ann Dermatol Venereol 2008;135:131—3. [4] Bhatti I, Cohen SN, Bleiker T, Lund J, Tierney G. Nicorandilinduced foreskin ulceration. Colorectal Dis 2009;11:424—5. [5] Birnie A, Dearing N, Littlewood S, Carlin E. Nicorandilinduced ulceration of the penis. Clin Exp Dermatol 2008;33:215—6.
Available online at www.sciencedirect.com