Dystrophic Penile Calcification in Peyronie’s Disease

0022-534 7/88/1394-0738$2.00/0 Vol. 139, April Printed in U.S.A.

THE JOURNAL OF UROLOGY

Copyright © 1988 by The Williams & Wilkins Co.

DYSTROPHIC PENILE CALCIFICATION IN PEYRONIE'S DISEASE MARTIN K. GELBARD From the Division of Uro/,ogy, UCLA School of Medicine, Los Angeles, California

ABSTRACT

Plain film radiography was performed in 66 consecutive patients with Peyronie's disease. Dystrophic calcification was noted in 22 patients (33 per cent). Patients with dystrophic calcification were younger (p less than 0.025) and had a more severe deformity (p less than 0.05) than those without calcification. (J. Urol., 139: 738-740, 1988) Peyronie's disease is a localized disorder of connective tissue affecting the tunica albuginea of the corpus cavernosum. Its presentation clinically ranges from that of an asymptomatic palpable nodule to erectile pain associated with marked penile deformity. Severe cases commonly impede or preclude intercourse. While history and physical examination provide the diagnosis in all cases, several ancillary imaging studies have been described, including plain film radiography, 1 corpus cavernosography,2·3 ultrasound, 1 •4 xeroradiography and computerized tomography (CT). 5 These studies have all been advanced as objective means of documentation and methods to chart serially the progress of the disease process. To date, no studies have shown any correlation between radiographic findings and clinical features of the disease. This study represents the analysis of several clinical parameters in 66 consecutive, unselected men with Peyronie's disease undergoing plain film penile radiography. MATERIALS AND METHODS

Between October 1985 and July 1986, 66 patients 23 to 79 years old were evaluated for Peyronie's disease. In addition to a routine urological history and physical examination, these men were evaluated for duration of disease, pattern of onset (whether pain or bending was noticed first), severity of bend (categorized as 1-less than 30 degrees, 2-between 30 and 45 degrees, 3-45 to 60 degrees and 4-greater than 60 degrees of penile deviation), history of coital or penile trauma, ability to have intercourse and the presence of Dupuytren's contracture. All patients underwent penile plain film radiography with a technique developed by Dr. Charles J. Devine, Jr. The patient is positioned supine, with the genitalia directly below the x-ray tube. He then stretches the penis upward by holding the glans only. A dorsal view is taken by pulling the penis downward over the film, which is held horizontally over the thighs, followed by a lateral view taken by laying the penis laterally over the film. By shielding half of a single sheet of individually wrapped 5 X 7-inch film (Kodak X-Omat AR-2) with a metal plate a dorsal view is obtained and then by exchanging sides and shielding the exposed portion of the film a lateral view is obtained on the same piece of film. Exposure was 30 kV. at 100 ma. for sixth-tenths of a second. This low kilovolt technique is sensitive enough to detect small changes in soft tissue density and small areas of calcification. Values for the aforementioned clinical parameters then were compared between patients with and without calcification. These comparisons were analyzed for statistical significance with a paired Student's t test for numerical values and chisquare analysis for results expressed as a percentage.

RESULTS

There were no difficulties in producing technically good films and satisfactory images were obtained in all patients. Of the patients studied 22 (33.3 per cent) demonstrated calcification visible by the plain film technique. The extent or distribution of dystrophic calcification was not subject to statistical analysis but it was found that calcification paralleled the palpable lesions noted on examination. Most areas of calcification were dorsal (fig. 1), although ventral plaques were noted in some cases (fig. 2), as well as calcification involving the intercorporeal septum (fig. 3). Occasionally, intercorporeal calcification linked dorsal and ventral plates of dystrophic calcification, forming an I-beam configuration (fig. 4). Statistical differences in clinical disease parameters between the calcified and noncalcified groups are shown in the table. The difference in prevalence of Dupuytren's contracture was not significant owing to the small sample size in this subgroup. Of interest was that all patients in the calcified group with Dupuytren's contracture also had a family history of this condition, while no patient with Dupuytren's contracture in the noncalcified group had such a family history.

Accepted for publication August 18, 1987.. . . Read at annual meeting of Western Section, American Urological Association, Seattle, Washington, July 27-31, 1986.

FIG. 1. Linear dorsal calcification. A, lateral view. B, dorsal view 738

DYSTROPHIC PENILE CALCIFICATION IN PEYRONIE'S DISEASE

FIG. 2. "Filmy" ventral calcification near base of penis. A, lateral view. B, dorsal view. FIG. 4. Small dorsal calcifications linked to larger ventral calcification by columnar septal spur seen vertically in lateral view (A) and end-on in dorsal view (B). Disease parameters Calcification Calcification Present Absent (22 pts.) (44 pts.) Av. age (yrs.) Av. duration (yrs.) Onset pattern(%): Pain Bending Av. severity (1-4) Trauma(%) Able to have intercourse (%) Dupuytren's contracture (%)

FIG. 3. Proximal ring-like septal calcification and linear dorsal calcification. Note trabecular texture of proximal plaque, similar in appearance to cancellous bone. A, lateral view. B, dorsal view.

P Value

48 2.3

55 1.7

<0.025 Not significant

60 40 2.9 9 78 9

34 66 2.5 9 60 18

Not significant Not significant <0.05 Not significant Not significant Not significant

The difference in the ability to have intercourse between calcified and noncalcified patients was not significant. This is not surprising, based on the complex nature of this capacity and the broad latitude allowed for interpretation of this question. No difference was found in regard to a history of trauma between the 2 groups. While it appeared that patients with calcified plaques more commonly presented with pain before bending, this difference was not statistically significant. Although the data showed a difference between the 2 groups in duration of disease, it was not statistically significant. The lack of significance was attributed to the high variability of this parameter, with the mean plus or minus standard deviation of 1.4 years in the calcified group and 1.8 years in the noncalcified group, compared to their respective means of 2.3 and 1. 7 years. A significant difference between the 2 groups was found in regard to patient age and disease severity. The difference in age was significant to the p <0.025 level with a mean plus or minus standard deviation of 8.8 years in the calcified group and 12.7 years in the noncalcified group. Disease severity, graded on a scale of 1 to 4, was significantly different at p <0.05. The mean plus or minus standard deviation for severity was 0. 7 and 0.8, respectively, with and without calcification.

740

GELBARD DISCUSSION

Plain film radiography of the penis is a technique that can be accomplished with basic x-ray facilities. While this imaging modality provides less information than ultrasound or CT, the dystrophic calcification detected in a third of the patients with this disorder segregate them into a subset with relatively more penile deformity occurring at a younger age. This incidence is similar to the 30 per cent figure cited by Vande berg and associates in their ultrastructural study of 20 patientsa and less than the 48 per cent incidence found in a series of CT examinations. 5 Patient selection in these previous studies was not described but the 33 per cent incidence in the present series of consecutive unselected patients would suggest that penile dystrophic calcification is a fairly common event in patients with Peyronie's disease. The data do not permit correlation of disease evolution with this radiographic finding, although others have written "Calcification represents a phase in Peyronie's disease when the prevailing methods of chemical and radiation therapy have minimal effect". a Dystrophic calcification in the connective tissues of patients with dermatomyositis reduces the chances of full functional recovery when compared to patients without calcification.7 The presence of dystrophic calcification is thought to be an indication for surgery when associated with a disabling deformity for at least 1 year in duration, the history of an adequate trial of conservative or medical therapy and an acceptable psychological status. This last factor bears emphasis in those patients with penile dystrophic calcification, since younger, more sexually active patients with considerable penile deformity are likely to experience significant psychological difficulty. The etiology of Peyronie's disease is unknown, which limits the analysis of the mechanism of calcification in these patients. No abnormalities in the serum calcium levels of patients with Peyronie's disease have been identified.a Similarly, patients with pathological soft tissue dystrophic calcification in various collagen vascular diseases do not have any systemic abnormalities in calcium metabolism. 8 Pathological calcification is noted first as an electron dense deposit on collagen fibrils that demonstrate reduced periodicity. These areas also demonstrate elastogenesis in the ground substance between collagen fibers. 9 Calcification appears to begin adjacent to vascular areas that demonstrate the characteristic perivascular round cell accumulation of early Peyronie's disease. With continued calcification areas of dystrophic mineralization demonstrate at times true bony metaplasia, either with a lamellar "Haversian" appearance of cortical bone or a trabecular appearance of cancellous bone.a Although connective tissue crystal deposition appears unlikely as an initiator of the inflammatory response in all patients with this disorder, it may have a secondary role in continuation of the inflammatory process in patients with calcification. It has been shown that ectopic apatite deposits in connective tissue can cause a significant inflammatory response.10· 11 This is consistent with my impression that the occasional patient with "active" or progressive Peyronie's disease more frequently demonstrates the presence of dystrophic calcification on plain film examination. The mean duration of disease for all patients in this series was 2 years, with a slight but statistically insignificant increase in patients with dystrophic calcification. Ossification generally is seen in long-standing lesions, although patients with calcification appearing early in the disease process have been described. These patients may form a group predisposed to a more accelerated form of fibrosis, who even several years into the disease process continue to display the vasculitic histology usually seen in lesions of short duration. 9 Histological studies have shown the calcified plaques to be surrounded by dense fibrous connective tissue. A recent study with CT imaging has revealed an interesting variation in radio-

graphic density in the tunica albuginea surrounding calcified plaques. 5 Of 9 patients with calcification 7 demonstrated plaques surrounded by a "halo" of hypodense tunica albuginea, while in 2 the plaques were continuous with normally dense tunica albuginea. In 11 plaques not calcified a diminished CT density was noted compared to normal tunica albuginea. The reduction in radiographic density has been attributed to tissue edema, as opposed to dense established scar or connective tissue. Calcified lesions continuous with normal tunica albuginea probably represent a clinically stable situation but the presence of calcification surrounded by hypodense (inflammatory) tissue may represent "active" or progressive disease. In conclusion, plain film radiography isolates among patients with Peyronie's disease a subgroup with dystrophic calcification, earlier onset and more severe degrees of penile deformity. REFERENCES

L Mohar, N.: lnduration penis plastica ossificans-possibilities of radiologic and diagnostic ultrasound interpretation. Acta Med. lugosl., 34: 405, 1980. 2. Velcek, D. and Evans, J. A.: Cavernosography. Radiology, 144: 781, 1982. 3. Gray, R., Grossman, H., St. Louis, E. and Leekam, R.: The uses of corpus cavernosography. A review. J. Canad. Ass. Rad., 35: 338, 1984. 4. Gelbard, M., Sarti, D. and Kaufman, J. J.: Ultrasound imaging of Peyronie's plaques. J. Urol., 125: 44, 1981. 5. Rollandi, G. A., Tentarelli, T. and Vespier, M.: Computed tomographic findings in Peyronie's disease. Urol. Rad., 7: 153, 1985. 6. Vandeberg, J. S., Devine, C. J., Jr., Horton, C. E., Somers, K. D., Wright, G. L., Jr., Leffell, M. S., Dawson, D. M., Gleishman, S. H. and Rowe, M. J.: Mechanisms of calcification in Peyronie's disease. J. Urol., 127: 52, 1985. 7. Nielsen, A. 0., Johnson, E., Hentzer, B. and Kobayasi, T.: Dermatomyositis with universal calcinosis. A histopathological and electron optic study. J. Cutan. Path., 6: 486, 1979. 8. Wheeler, C. E., Curtis, A. C., Cawley, E. P., Grekin, R. H. and Zheutlin, B.: Soft tissue calcification with special reference to its occurrence in the "collagen diseases." Ann. Intern. Med., 36: 1050, 1952. 9. Vandeberg, J. S., Devine, C. J., Jr., Horton, C. E., Somers, K. D., Wright, G. L., Jr. Leffell, M. S., Dawson, D. M., Gleishman, S. H. and Rowe, M. J.: Peyronie's disease: an electron microscopic study. J. Urol., 126: 333, 1981. 10. Taborn, J., Bole, G. G. and Thompson, G. R.: Colchicine suppression of local and systemic inflammation due to calcinosis universalis in chronic dermatomyositis. Ann. Intern. Med., 89: 648, 1978. 11. Denko, C. W. and Whitehouse, M. W.: Experimental inflammation induced by naturally occurring microcrystalline calcium salts. J. Rheum., 3: 54, 1976.

EDITORIAL COMMENT The author relates his experience with calcification in Peyronie's disease plaques. In 66 patients he found calcification in one-third. In a larger group of patients we have found calcification in one-fourth. His study of the effects of calcification reveal that function depends upon the distortion of the penis rather than the presence or absence of calcification, calcification does not imply a traumatic etiology, calcification may be associated with a higher incidence of pain before the bending, patients with calcification may have the disease longer than those without calcification, and patients with calcification "tend" to be younger and to have more severe disease. Although there was a statistical significance in patient age and disease severity, the series suffers from lack of numbers of patients involved. Sixty-six well studied patients is a large series but I am not certain that in a larger series the significance will fade. The most important part of this report is the author's speculations about the pathological process involved in the generation of the disease and his attempt to find parallels with other conditions in which calcification occurs. These insights open more aspects of Peyronie's disease, which once thought simple is now revealed to be much more complex. Charles J. Devine, Jr. Hague Medical Center Norfolk, Virginia