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Subcutaneous penile vein thrombosis (Penile Mondor’s Disease): Pathogenesis, diagnosis, and therapy
ADULT UROLOGY
SUBCUTANEOUS PENILE VEIN THROMBOSIS (PENILE MONDOR’S DISEASE): PATHOGENESIS, DIAGNOSIS, AND THERAPY M. AL-MWALAD, H. LOERTZER, A. WICHT,
AND
P. FORNARA
ABSTRACT Objectives. In international studies, only a few data are available on subcutaneous penile vein thrombosis. The pathogenesis is unknown, and no general recommendation exists regarding therapy. Methods. A total of 25 patients with the clinical picture of a “superficial penile vein thrombosis” were treated at our policlinic. All patients had noted sudden and almost painless indurations on the penile dorsal surface. The extent of the thrombosis varied. Detailed anamnesis, ultrasonography, and routine laboratory tests were performed for all patients, knowing that primary therapy was conservative. Results. No patient indicated any pain. Some reported a feeling of tension in the area of the thrombosis. In all patients, the thrombosis occurred in the dorsal penis shaft. It was close to the sulcus coronarius in 21 patients, near the penis root in 3, and in the entire penis shaft in 1 patient. The length of the thrombotic vein was between 2 and 4 cm. The ultrasound results were similar for all patients. The primary treatment was conservative for all patients. Recovery was achieved in more than 92% of cases (23 of 25 patients) using conservative therapy, which consisted of local dressing with heparin ointment (10,000 IU) and oral application of an antiphlogistic for 14 days. In 2 cases, thrombectomy was necessary. Conclusions. Extended imaging diagnosis does not improve the evaluation of the extent of a superficial penile vein thrombosis. Conservative primary therapy consisting of heparin ointment and oral application of antiphlogistics is sufficient. If the thrombosis persists after conservative therapy, surgery is indicated. UROLOGY 67: 586–588, 2006. © 2006 Elsevier Inc.
S
uperficial vein thrombosis was first described by Mondor1 in 1939. This form of phlebitis was observed exclusively at the thoracic wall. In 1955, Braun-Falco2 described penile participation as a superficial phlebitis. An isolated superficial penile vein thrombosis was first reported by Helm and Hodge3 in 1958. According to Kluten,4 it can also occur in the extremities. The pathogenesis is unknown. A traumatic genesis has been discussed, as well as locally confined toxic processes. We report on the largest current monocentric study regarding therapy for isolated superficial penile vein thrombosis.
MATERIAL AND METHODS We treated 25 patients with the clinical picture of a superficial penile vein thrombosis from April 1999 to March 2005. The average age was 35 years (range 15 to 57). The average period of observation was 35.9 months (range 2 to 83). All patients had observed a sudden and almost painless subcutaneous induration of the dorsal penis surface. The extent of the thrombosis varied. For all patients, detailed anamnesis, ultrasonography (Doppler ultrasonography of pelvic blood vessels and penile vessels), and routine laboratory analysis (electrolytes, blood count, C-reactive protein, and coagulation) were performed. Primary therapy was conservative, with local application of a heparin ointment (10,000 IU) and oral application of an antiphlogistic (indomethacin) for 14 days.
RESULTS From the University Clinic and Policlinic for Urology, MartinLuther University Halle-Wittenberg, Halle, Germany Reprint requests: Hagen Loertzer, M.D., University Clinic and Policlinic for Urology, Martin-Luther University Halle-Wittenberg, Ernst-Grube-Strasse 40, Halle 06097, Germany. E-mail: [email protected] Submitted: April 3, 2005, accepted (with revisions): September 29, 2005 © 2006 ELSEVIER INC. 586
ALL RIGHTS RESERVED
No patient reported any pain, but some described a feeling of tension in the area of the thrombosis. In 2 cases, the disease was noted in relation to erectile dysfunction. No signs of acute inflammation could be detected in any patient. Thrombosis occurred at the dorsal penis shaft in all patients, close to the sulcus coronarius in 21 patients, near the 0090-4295/06/$32.00 doi:10.1016/j.urology.2005.09.054
FIGURE 1. Doppler ultrasound image showing superficial penile vein thrombosis. Venous perfusion not detectable.
penis root in 3, and in the entire penis shaft in 1 patient. The length of the thrombotic vein was between 2 and 4 cm, but in 1 patient, it was more than 9 cm and involved several veins in the penile shaft. Thrombosis occurred after prolonged sexual intercourse in 1 patient (age 44), after application of a vacuum erection device in a 53-year-old patient, and during regression of purulent urethritis in a 23-year-old patient. The standard laboratory tests were without pathologic findings for all 24 patients. For 20 patients, with normal general and sexual anamnesis, idiopathic penile vein thrombosis was diagnosed. In the anamnesis, no immediate cause for the clinically manifest penile Mondor phlebitis was apparent. Five of these patients underwent in-depth laboratory analysis and imaging to elucidate the pathogenesis. The laboratory findings indicated a deficiency of free protein S in three of these patients. Additional imaging (magnetic resonance tomography and Doppler ultrasonography) excluded expansion and thrombosis of the veins in the pelvis or legs. The ultrasound findings were similar for all patients. An echo-dense structure was found in the adjoining blood vessel segments. Doppler ultrasonography did not detect venous flow signals in this area of the blood vessel (Fig. 1). The inner penile veins appeared normal. In 23 patients, the findings showed significant regression after a few days of conservative therapy, which consisted of a dressing with heparin ointment and oral application of an antiphlogistic (indomethacin). Prophylactic application of an antibiotic was intentionally omitted. Neither a local nor systemic infection developed in any patient. Even after 4 weeks of conservative treatment, idiopathic superficial penile vein thrombosis persisted in 2 patients who had not shown any signs of resolution. Therefore, they underwent surgery (Figs. 2 and 3). UROLOGY 67 (3), 2006
FIGURE 2. Intraoperative situs of superficial penile vein thrombosis.
FIGURE 3. Completely removed thrombus.
Histologic analysis confirmed the clinical diagnosis. In 1 patient, thrombophlebitis reappeared, about 8 weeks after surgery, in multiple penile blood vessel segments. This patient had a deficiency of free protein S (18%, normal range 31% to 47%), with normal protein S activity (94%, normal range more than 70%) and concentration (116%, normal range 81% to 113%), an increase in lipoprotein A, and a heterozygous MTHFR C677T mutation. Systemic anticoagulation, starting with heparin, followed by Marcumar, lead to regression of the disorder within 4 months. This patient has been under close observation and has fully recovered so far. COMMENT Published data on the superficial penile vein thrombosis are sparse and consist mostly of singlecase studies. Some investigators reported on more than 5 patients.5–10 All together, 44 cases have been described. 587
The pathogenesis of penile Mondor phlebitis is unclear. Trauma, strong sexual activity, tumors in the small pelvis, and surgery of the pelvis or in the area of the genitals have been discussed.8,11,12 For idiopathic penile thromboses, protein S deficiency can be considered a risk factor.13 Protein S is an anti-thrombus plasma protein acting as a cofactor for another plasma protein (activated protein C). Deficiency of antithrombin III, protein C, and protein S represent important genetic factors for venous thrombosis.14 –17 These defects are found in 15% to 20% of all families with thrombophilia.17 The diagnosis of superficial penile vein thrombosis can be established from the anamnesis and local observation. The patient age is usually 15 to 57 years. In our observational study, the average age was 34 years, and the oldest patient was 57. Almost all male age groups, except senior and prepubertal age were represented. Ultrasound and Doppler ultrasound examinations were sufficient to evaluate the extent of the thrombosis.10,11 According to the results of our study and those in published studies, additional invasive diagnostic procedures do not provide more information on the extent of the thrombosis5–10 and were thus deemed unnecessary. For additional clarification and in the case of a conspicuous anamnesis, imaging techniques may yield an indication of the pathogenesis and usually serve to exclude the possibility of tumor.8,11,12 Primary treatment with antiphlogistics and a local dressing with a heparin ointment proved to have very good results in most cases. We were able to show a success rate for conservative therapy of 92% (23 of 25 patients). Only in those rare cases in which the situation does not improve or even deteriorates, should thrombectomy be performed. Prophylactic application of an antibiotic can be omitted. The long-term results after conservative or surgical treatment of superficial penile vein thrombosis have not been reported.5–10 CONCLUSIONS The pathogenesis of subcutaneous penile vein thrombosis is still unclear. Furthermore, extended imaging studies usually do not provide any additional information. For the evaluation of a possible relapse or possible pathogenesis, the determination of protein S, free protein S, antithrombin III, and protein C levels can be helpful. Primary con-
588
servative therapy should consist of oral application of an antiphlogistic (indomethacin) and the local application of a heparin ointment. This will be sufficient in most cases. When thrombosis persists after sufficient conservative therapy, surgical treatment is indicated. REFERENCES 1. Mondor H: Tronculite sous-cutanée subaiguë de la paroi thoragigue antéro-latérale. Mem Acad Chir 65: 1271– 1278, 1939. 2. Braun-Falco O: Zur Klinik, Histologie und Pathogenese der strangförmigen, oberflächlichen Phlebitiden. Derm Wochenschr 132: 705–715, 1955. 3. Helm J, and Hodge I: Thrombophlebitis of a dorsal vein of the penis: report of a case treated by phenylbutazone (Butazolidin). J Urol 79: 306 –307, 1958. 4. Kluken N: Diagnosis and conservative treatment of thrombotic veinous processes in the extremities. Hefte Unfallkd 107: 124 –128, 1970. 5. Krause S, Lüdecke G, and Weidner W: Mondor’s disease of the penis. Urol Int 64: 99 –100, 2000. 6. Sasso F, Gulino G, Basar M, et al: Penile Mondors’ disease: an underestimated pathology. BJU Int 77: 729 –732, 1996. 7. Lilas LA, Mumtaz FH, Madders DJ, et al: Phimosis after penile Mondor’s phlebitis. BJU Int 83: 520 –521, 1999. 8. Swierzewski SJ, Denil J, and Ohl DA: The management of penile Mondor’s phlebitis: superficial dorsal penile thrombosis. J Urol 150: 77–78, 1993. 9. Katz R, and Blachar A: Superficial dorsal penile vein thrombosis (Mondor’s disease). Harefuah 132: 544 –545, 1997. 10. Ozkara H, Akkus E, Alici B, et al: Superficial dorsal penile vein thrombosis (penile Mondor’s disease). Int Urol Nephrol 28: 387–391, 1996. 11. Harrow B, and Sloane J: Thrombophlebitis of superficial penile and scrotal veins. J Urol 89: 841– 842, 1963. 12. McLaren AJ, Riazuddin N, and Northeast AD: Mondor meets Trendelenburg: penile vein thrombosis after varicose vein surgery. J R Soc Med 94: 292–293, 2001. 13. Girolami A, Simioni P, Scarano L, et al: Venous and arterial thrombophilia. Haematologica 82: 96 –100, 1997. 14. Pabinger I, and Schneider B: Thrombotic risk in hereditary antithrombin III, protein C, or protein S deficiency: a cooperative, retrospective study—Gesellschaft fur Thrombose und Hamostaseforschung (GTH) Study Group on Natural Inhibitors. Arterioscler Thromb Vasc Biol 16: 742–748, 1996. 15. Sanson BJ, Simioni P, Tormene D, et al: The incidence of venous thromboembolism in asymptomatic carriers of a deficiency of antithrombin, protein C, or protein S: a prospective cohort study. Blood 94: 3702–3706, 1999. 16. Comp PC, and Esmon CT: Recurrent venous thromboembolism in patients with a partial deficiency of protein S. N Engl J Med 311: 1525–1528, 1984. 17. Marz W, Nauck M, and Wieland H: The molecular mechanisms of inherited thrombophilia. Z Kardiol 89: 575– 586, 2000.
UROLOGY 67 (3), 2006
SUBCUTANEOUS PENILE VEIN THROMBOSIS (PENILE MONDOR’S DISEASE): PATHOGENESIS, DIAGNOSIS, AND THERAPY M. AL-MWALAD, H. LOERTZER, A. WICHT,
AND
P. FORNARA
ABSTRACT Objectives. In international studies, only a few data are available on subcutaneous penile vein thrombosis. The pathogenesis is unknown, and no general recommendation exists regarding therapy. Methods. A total of 25 patients with the clinical picture of a “superficial penile vein thrombosis” were treated at our policlinic. All patients had noted sudden and almost painless indurations on the penile dorsal surface. The extent of the thrombosis varied. Detailed anamnesis, ultrasonography, and routine laboratory tests were performed for all patients, knowing that primary therapy was conservative. Results. No patient indicated any pain. Some reported a feeling of tension in the area of the thrombosis. In all patients, the thrombosis occurred in the dorsal penis shaft. It was close to the sulcus coronarius in 21 patients, near the penis root in 3, and in the entire penis shaft in 1 patient. The length of the thrombotic vein was between 2 and 4 cm. The ultrasound results were similar for all patients. The primary treatment was conservative for all patients. Recovery was achieved in more than 92% of cases (23 of 25 patients) using conservative therapy, which consisted of local dressing with heparin ointment (10,000 IU) and oral application of an antiphlogistic for 14 days. In 2 cases, thrombectomy was necessary. Conclusions. Extended imaging diagnosis does not improve the evaluation of the extent of a superficial penile vein thrombosis. Conservative primary therapy consisting of heparin ointment and oral application of antiphlogistics is sufficient. If the thrombosis persists after conservative therapy, surgery is indicated. UROLOGY 67: 586–588, 2006. © 2006 Elsevier Inc.
S
uperficial vein thrombosis was first described by Mondor1 in 1939. This form of phlebitis was observed exclusively at the thoracic wall. In 1955, Braun-Falco2 described penile participation as a superficial phlebitis. An isolated superficial penile vein thrombosis was first reported by Helm and Hodge3 in 1958. According to Kluten,4 it can also occur in the extremities. The pathogenesis is unknown. A traumatic genesis has been discussed, as well as locally confined toxic processes. We report on the largest current monocentric study regarding therapy for isolated superficial penile vein thrombosis.
MATERIAL AND METHODS We treated 25 patients with the clinical picture of a superficial penile vein thrombosis from April 1999 to March 2005. The average age was 35 years (range 15 to 57). The average period of observation was 35.9 months (range 2 to 83). All patients had observed a sudden and almost painless subcutaneous induration of the dorsal penis surface. The extent of the thrombosis varied. For all patients, detailed anamnesis, ultrasonography (Doppler ultrasonography of pelvic blood vessels and penile vessels), and routine laboratory analysis (electrolytes, blood count, C-reactive protein, and coagulation) were performed. Primary therapy was conservative, with local application of a heparin ointment (10,000 IU) and oral application of an antiphlogistic (indomethacin) for 14 days.
RESULTS From the University Clinic and Policlinic for Urology, MartinLuther University Halle-Wittenberg, Halle, Germany Reprint requests: Hagen Loertzer, M.D., University Clinic and Policlinic for Urology, Martin-Luther University Halle-Wittenberg, Ernst-Grube-Strasse 40, Halle 06097, Germany. E-mail: [email protected] Submitted: April 3, 2005, accepted (with revisions): September 29, 2005 © 2006 ELSEVIER INC. 586
ALL RIGHTS RESERVED
No patient reported any pain, but some described a feeling of tension in the area of the thrombosis. In 2 cases, the disease was noted in relation to erectile dysfunction. No signs of acute inflammation could be detected in any patient. Thrombosis occurred at the dorsal penis shaft in all patients, close to the sulcus coronarius in 21 patients, near the 0090-4295/06/$32.00 doi:10.1016/j.urology.2005.09.054
FIGURE 1. Doppler ultrasound image showing superficial penile vein thrombosis. Venous perfusion not detectable.
penis root in 3, and in the entire penis shaft in 1 patient. The length of the thrombotic vein was between 2 and 4 cm, but in 1 patient, it was more than 9 cm and involved several veins in the penile shaft. Thrombosis occurred after prolonged sexual intercourse in 1 patient (age 44), after application of a vacuum erection device in a 53-year-old patient, and during regression of purulent urethritis in a 23-year-old patient. The standard laboratory tests were without pathologic findings for all 24 patients. For 20 patients, with normal general and sexual anamnesis, idiopathic penile vein thrombosis was diagnosed. In the anamnesis, no immediate cause for the clinically manifest penile Mondor phlebitis was apparent. Five of these patients underwent in-depth laboratory analysis and imaging to elucidate the pathogenesis. The laboratory findings indicated a deficiency of free protein S in three of these patients. Additional imaging (magnetic resonance tomography and Doppler ultrasonography) excluded expansion and thrombosis of the veins in the pelvis or legs. The ultrasound findings were similar for all patients. An echo-dense structure was found in the adjoining blood vessel segments. Doppler ultrasonography did not detect venous flow signals in this area of the blood vessel (Fig. 1). The inner penile veins appeared normal. In 23 patients, the findings showed significant regression after a few days of conservative therapy, which consisted of a dressing with heparin ointment and oral application of an antiphlogistic (indomethacin). Prophylactic application of an antibiotic was intentionally omitted. Neither a local nor systemic infection developed in any patient. Even after 4 weeks of conservative treatment, idiopathic superficial penile vein thrombosis persisted in 2 patients who had not shown any signs of resolution. Therefore, they underwent surgery (Figs. 2 and 3). UROLOGY 67 (3), 2006
FIGURE 2. Intraoperative situs of superficial penile vein thrombosis.
FIGURE 3. Completely removed thrombus.
Histologic analysis confirmed the clinical diagnosis. In 1 patient, thrombophlebitis reappeared, about 8 weeks after surgery, in multiple penile blood vessel segments. This patient had a deficiency of free protein S (18%, normal range 31% to 47%), with normal protein S activity (94%, normal range more than 70%) and concentration (116%, normal range 81% to 113%), an increase in lipoprotein A, and a heterozygous MTHFR C677T mutation. Systemic anticoagulation, starting with heparin, followed by Marcumar, lead to regression of the disorder within 4 months. This patient has been under close observation and has fully recovered so far. COMMENT Published data on the superficial penile vein thrombosis are sparse and consist mostly of singlecase studies. Some investigators reported on more than 5 patients.5–10 All together, 44 cases have been described. 587
The pathogenesis of penile Mondor phlebitis is unclear. Trauma, strong sexual activity, tumors in the small pelvis, and surgery of the pelvis or in the area of the genitals have been discussed.8,11,12 For idiopathic penile thromboses, protein S deficiency can be considered a risk factor.13 Protein S is an anti-thrombus plasma protein acting as a cofactor for another plasma protein (activated protein C). Deficiency of antithrombin III, protein C, and protein S represent important genetic factors for venous thrombosis.14 –17 These defects are found in 15% to 20% of all families with thrombophilia.17 The diagnosis of superficial penile vein thrombosis can be established from the anamnesis and local observation. The patient age is usually 15 to 57 years. In our observational study, the average age was 34 years, and the oldest patient was 57. Almost all male age groups, except senior and prepubertal age were represented. Ultrasound and Doppler ultrasound examinations were sufficient to evaluate the extent of the thrombosis.10,11 According to the results of our study and those in published studies, additional invasive diagnostic procedures do not provide more information on the extent of the thrombosis5–10 and were thus deemed unnecessary. For additional clarification and in the case of a conspicuous anamnesis, imaging techniques may yield an indication of the pathogenesis and usually serve to exclude the possibility of tumor.8,11,12 Primary treatment with antiphlogistics and a local dressing with a heparin ointment proved to have very good results in most cases. We were able to show a success rate for conservative therapy of 92% (23 of 25 patients). Only in those rare cases in which the situation does not improve or even deteriorates, should thrombectomy be performed. Prophylactic application of an antibiotic can be omitted. The long-term results after conservative or surgical treatment of superficial penile vein thrombosis have not been reported.5–10 CONCLUSIONS The pathogenesis of subcutaneous penile vein thrombosis is still unclear. Furthermore, extended imaging studies usually do not provide any additional information. For the evaluation of a possible relapse or possible pathogenesis, the determination of protein S, free protein S, antithrombin III, and protein C levels can be helpful. Primary con-
588
servative therapy should consist of oral application of an antiphlogistic (indomethacin) and the local application of a heparin ointment. This will be sufficient in most cases. When thrombosis persists after sufficient conservative therapy, surgical treatment is indicated. REFERENCES 1. Mondor H: Tronculite sous-cutanée subaiguë de la paroi thoragigue antéro-latérale. Mem Acad Chir 65: 1271– 1278, 1939. 2. Braun-Falco O: Zur Klinik, Histologie und Pathogenese der strangförmigen, oberflächlichen Phlebitiden. Derm Wochenschr 132: 705–715, 1955. 3. Helm J, and Hodge I: Thrombophlebitis of a dorsal vein of the penis: report of a case treated by phenylbutazone (Butazolidin). J Urol 79: 306 –307, 1958. 4. Kluken N: Diagnosis and conservative treatment of thrombotic veinous processes in the extremities. Hefte Unfallkd 107: 124 –128, 1970. 5. Krause S, Lüdecke G, and Weidner W: Mondor’s disease of the penis. Urol Int 64: 99 –100, 2000. 6. Sasso F, Gulino G, Basar M, et al: Penile Mondors’ disease: an underestimated pathology. BJU Int 77: 729 –732, 1996. 7. Lilas LA, Mumtaz FH, Madders DJ, et al: Phimosis after penile Mondor’s phlebitis. BJU Int 83: 520 –521, 1999. 8. Swierzewski SJ, Denil J, and Ohl DA: The management of penile Mondor’s phlebitis: superficial dorsal penile thrombosis. J Urol 150: 77–78, 1993. 9. Katz R, and Blachar A: Superficial dorsal penile vein thrombosis (Mondor’s disease). Harefuah 132: 544 –545, 1997. 10. Ozkara H, Akkus E, Alici B, et al: Superficial dorsal penile vein thrombosis (penile Mondor’s disease). Int Urol Nephrol 28: 387–391, 1996. 11. Harrow B, and Sloane J: Thrombophlebitis of superficial penile and scrotal veins. J Urol 89: 841– 842, 1963. 12. McLaren AJ, Riazuddin N, and Northeast AD: Mondor meets Trendelenburg: penile vein thrombosis after varicose vein surgery. J R Soc Med 94: 292–293, 2001. 13. Girolami A, Simioni P, Scarano L, et al: Venous and arterial thrombophilia. Haematologica 82: 96 –100, 1997. 14. Pabinger I, and Schneider B: Thrombotic risk in hereditary antithrombin III, protein C, or protein S deficiency: a cooperative, retrospective study—Gesellschaft fur Thrombose und Hamostaseforschung (GTH) Study Group on Natural Inhibitors. Arterioscler Thromb Vasc Biol 16: 742–748, 1996. 15. Sanson BJ, Simioni P, Tormene D, et al: The incidence of venous thromboembolism in asymptomatic carriers of a deficiency of antithrombin, protein C, or protein S: a prospective cohort study. Blood 94: 3702–3706, 1999. 16. Comp PC, and Esmon CT: Recurrent venous thromboembolism in patients with a partial deficiency of protein S. N Engl J Med 311: 1525–1528, 1984. 17. Marz W, Nauck M, and Wieland H: The molecular mechanisms of inherited thrombophilia. Z Kardiol 89: 575– 586, 2000.
UROLOGY 67 (3), 2006