A rare cause of recurrent priapism: hereditary angioedema M. Akyuz1, C. Kaya1 & M. F. Akdogan2 1 Urology Clinics, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey; 2 Internal Medicine Clinics, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey
Keywords Erectile dysfunction—priapism Correspondence Mehmet Akyuz, Haydarpasa Numune Training and Research Hospital, Urology, Tibbiye cad no:40, Istanbul 81190, Turkey. Tel. +90 21 6414 5402; Fax: +90 21 6345 5982; E-mail: [email protected]
Summary Hereditary angioedema is a rare disease, which is caused by deficiency of compleman c1 esterase inhibitor regulatory protein in the compleman system. Priapism is involuntary, painful and prolonged erection of penis more than 4 h without sexual desire. In this case report, we elucidated a patient diagnosed with hereditary angioedema while he had recurrent priapism.
Accepted: April 11, 2014 doi: 10.1111/and.12297
Introduction Hereditary angipedema (HA) is a rare disease, which is caused by deficiency of compleman c1 esterase inhibitor regulatory protein in the compleman system. Although its prevalence is not exactly known, it is thought that this disease is seen at a rate of 1/10.000–50.000 (Agostoni et al., 2004; Bowen et al., 2004; Gompels et al., 2005; Bork et al., 2007). Clinically it is mostly seen on hands, face, body, lower extremities and genital region as nonitching and recurrent subcutaneous oedema. On the other hand, laryngeal oedema, which is a most severe complication, can cause asphyxia and even death. Clinical signs arise from deficiency of C1 esterase inhibitor which lead to capillary dilatation, increase in vascular permeability and smooth muscle relaxation by the way of activation of lots of c1, which cause secretion of inflammatory mediators like kinin-like peptides and bradykinin (Nielsen et al., 1996; Frank, 2004). Priapism is involuntary, painful and prolonged erection of penis more than 4 h without sexual desire. It is a compartment syndrome of the penis and may lead to end-organ damage and ED. It may occur due to obstruction of blood flow out of the penis through penile veins and/or failure of the smooth muscle within the spongy erectile tissue of the penis to contract normally. Although haematopoietic system diseases, malignancies, drugs like antipsychotics and intracavernosal agents and perineal trauma can lead to priapism, idiopathic cases can also be seen. Priapism can be divided into three 600
groups: ischaemic (low-flow, veno-occlusive), nonischaemic (high-flow) and recurrent (Pryor et al., 2004; Broderick et al., 2010). Without early treatment in 12 h, erectile dysfunction can occur because of necrosis in the penile erectile tissue and irreversible changes in corporeal tissue as a result of prolonged ischaemia (Montague et al., 2003; Cherian et al., 2006). The initial management of priapism should be corporeal aspiration with injection of sympathomimetic agents. If medical management fails, a cavernosal shunt procedure is indicated. In this case report, we elucidated a patient diagnosed with HA while he had recurrent priapism. To the best of our knowledge, priapism caused by HA was not reported before in the literature. Case report We evaluated a 33-year-old male patient who had five times priapism in the last 3 years. He was treated with cavernous aspiration in the first three attacks and then distal shunt operation was performed in the last two attacks. On patient history taking for aetiology of priapism, we found nothing about drugs or neurological and haematological diseases that can cause priapism. When we took history in detail, we found out that the patient had presented to the emergency clinic many times because of stomachache. In evaluation of patient who had family members with FMF, there were no related mutations in genetic examination. An endoscopic procedure © 2014 Blackwell Verlag GmbH Andrologia 2015, 47, 600–602
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was performed after mucosal oedema was seen in the abdominal CT (Fig. 1), but no pathology was found. In recurrent stomachache periods, the patient experienced priapism attack after painful oedema in hands, lips and face (Fig. 2). The complement component C4 was 14 mg/dl, which is lower than normal (16–38). C1 esterase inhibitor was 7 mg/dl. (18–32). Function of C1 esterase inhibitor was 54.0% (70–132). We started 1000 IU C1 esterase infusion during the priapism attack and then the patient had no priapism attack for 1 year. Discussion C1 esterase inhibitor is a regulatory protein of classic way of complement system, kinin-kallikrein and fibrinolytic system. HA is caused by absence of C1 esterase inhibitor and it goes with recurrent nonitching oedema. In HA,
Fig. 1 Submucosal oedema in small intestine during stomachache attack.
Fig. 2 Oedema in hands while attack.
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complement system is activated uncontrolled and oedema occurs by increase in vascular permeability and dilatation (Agostoni et al., 2004; Gompels et al., 2005; Bork et al., 2007). HA is distinguished from angioneurotic oedema by absence of histamine in pathogenesis. Type 1 in which level of C1 esterase inhibitor is low is most common. Type 2 in which function of C1 esterase inhibitor is low and type 3 unrelated with function are more rarely seen. The frequency of HA is not different in males and females. Trauma, stress, hormonal changes, infection and surgical interventions to head and neck can trigger HA attacks. Symptoms generally start in adolescence. The frequency of attacks can be weekly or yearly and it changes from patient to patient (Witschi et al., 1996; Agostoni et al., 2004; Frank, 2004). A general symptom of HA is nonitching and painless oedema mostly in hands, face, body and legs. Patients describe oedema in hands as a longer hand and for foot they say that they could not wear their shoes. Facial oedema can cause social isolation because of abnormal appearance. Our patient complained about recurrent oedema on hands and lips. Laryngeal oedema can occur as a severe complication of HA after surgery of neck and teeth by way of spreading oedema to larynx. Exact diagnosis of the patient is often delayed because of undetailed medical history (Agostoni et al., 2004; Bork et al., 2007). Recurrent abdominal pain because of submucosal oedema in the bowel wall can lead the patient to resort to emergency clinic and also gastroenterology clinic (Nielsen et al., 1996; Witschi et al., 1996). Our patient’s main complaint was recurrent abdominal pain. There was no pathology in routine laboratory test, gastroscopy colonoscopy and even biopsy of bowel. In HA, subcutaneous oedema can occur in the genital area. In our literature scan, we can only find one case with genital oedema but we could not find priapism cases (Dhairyawan et al., 2011). ED can occur if treatment of priapism is not enough early. This can cause severely impaired quality of life (Pryor et al., 2004; Broderick et al., 2010). Our case is different in that ED did not occur after recurrent priapism and surgical intervention. Relaxation of penile smooth muscle (tissue) with different mechanisms can lead to priapism. So in the pathophysiology of priapism, we expect functional increase in the mechanism of penile smooth muscle tissue (Nielsen et al., 1996; Montague et al., 2003; Cherian et al., 2006). Our patient did not have any haematological or malignant disease and also did not use antipsychotic drug. So we think that in this case, bradykinin and other mediators can lead to priapism by capillary dilatation, increase in vascular permeability and smooth muscle relaxation. 601
We advised the patient to stay away from emotional stress and trauma to protect from attacks of HA. Prophylactic fresh frozen plasma can be used before head and neck surgery. Long-term use of androgens like danazol can decrease frequency of attacks (Nielsen et al., 1996; Bowen et al., 2004; Frank, 2004). In acute cases, the benefit of corticosteroids and antihistamines is limited. Concentrated recombinant C1 esterase agents are used during acute attacks. In our case, after this treatment, the patient’s clinical situation was getting better and no further attack of priapism was seen. As a result, HA should be kept in mind especially in patient with recurrent nonpainful oedema and family history. HA can be a reason for priapism in patients in whom an aetiological factor cannot be found. References Agostoni A, Ayg€ oren-P€ urs€ un E, Binkley KE, Blanch A, Bork K, Bouillet L, Bucher C, Castaldo AJ, Cicardi M, Davis AE, De Carolis C, Drouet C, Duponchel C, Farkas H, Fay K, Fekete B, Fischer B, Fontana L, F€ ust G, Giacomelli R, Gr€ oner A, Hack CE, Harmat G, Jakenfelds J, Juers M, Kalmar L, Kaposi PN, Karadi I, Kitzinger A, Kollar T, Kreuz W, Lakatos P, Longhurst HJ, Lopez-Trascasa M, Martinez-Saguer I, Monnier N, Nagy I, Nemeth E, Nielsen EW, Nuijens JH, O’grady C, Pappalardo E, Penna V, Perricone C, Perricone R, Rauch U, Roche O, Rusicke E, Sp€ath PJ, Szendei G, Takacs E, Tordai A, Truedsson L, Varga L, Visy B, Williams K, Zanichelli A, Zingale L (2004) Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol 114(Suppl 3):S51–S131. Bork K, G€ ul D, Hardt J, Dewald G (2007) Hereditary angioedema with normal C1 inhibitor: clinical symptoms and course. Am J Med 120:987–992. Bowen T, Cicardi M, Farkas H, Bork K, Kreuz W, Zingale L, Varga L, Martinez-Saguer I, Ayg€ oren-P€ urs€ un E, Binkley K, Zuraw B, Davis A 3rd, Hebert J, Ritchie B, Burnham J,
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Castaldo A, Menendez A, Nagy I, Harmat G, Bucher C, Lacuesta G, Issekutz A, Warrington R, Yang W, Dean J, Kanani A, Stark D, McCusker C, Wagner E, Rivard GE, Leith E, Tsai E, MacSween M, Lyanga J, Serushago B, Leznoff A, Waserman S, de Serres J (2004) Canadian 2003 international consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. J Allergy Clin Immunol 114:629–637. Broderick GA, Kadıoglu A, Bivalacqua TJ, Ghanem H, Nehra A, Shamloul R (2010) Priapism: pathogenesis, epidemiology and management. J Sex Med 7:476–500. Cherian J, Rao AR, Thwaini A, Kapasi F, Shergill IS, Samman R (2006) Medical and surgical management of priapism. Postgrad Med J 82:89–94. Dhairyawan R, Harrison R, Buckland M, Hourihan M (2011) Hereditary angioedema: an unusual cause of genital swelling presenting to a genitourinary medicine clinic. Int J STD AIDS 22:356–357. Frank MM (2004) Hereditary angioedema: a half century of progress. J Allergy Clin Immunol 114:626–628. Gompels MM, Lock RJ, Abinun M, Bethune CA, Davies G, Grattan C, Fay AC, Longhurst HJ, Morrison L, Price A, Price M, Watters D (2005) C1 inhibitor deficiency: consensus document. Clin Exp Immunol 139:379–394. Montague DK, Jarow J, Broderick GA, Dmochowski RR, Heaton JP, Lue TF, Nehra A, Sharlip ID (2003) American Urological Association guideline on the management of priapism. J Urol 170:1318–1324. Nielsen EW, Gran JT, Straume B, Mellby OJ, Johansen HT, Molness TE (1996) Hereditary angioedema: new clinical observations and autoimmune screening, complement and kallikrein-kinin analyses. J Intern Med 239:119–130. Pryor J, Akkusß E, Alter G, Jordan G, Lebret T, Levine L, Mulhall J, Perovic S, Ralph D, Stackl W (2004) Priapism. J Sex Med 1:116–120. Witschi A, Krahenb€ uhl L, Frei E, Saltzman J, Spath PJ, Muller UR (1996) Colorectal intussusception: an unusual gastrointestinal complication of hereditary angioedema. Int Arch Allergy Immunol 111:96–98.
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