2009: Orchitis and epididymitis Orchitis and epididymitis 1 R. B. Hollett 2 Department of Large Animal Medicine and Deans’ Office, College of Veterinary 3 Medicine, The University of Georgia, Athens GA, USA 4 Abstract 5 Inflammation of the male testis and/or epididymis produces canine and feline 6 subfertility and infertility. Causative agents include bacteria, trauma, non-infectious 7 immune-mediated response, prostatitis, urinary tract infection, or an accompanying 8 endocrine disorder. Each possible etiology should be evaluated to both determine the 9 reason for the abnormal reproductive function and to justify its treatment. 10 Keywords: Orchitis, epididymitis, dog, cat, Brucella 11 Introduction 12 In the male, loss of reproductive performance is sometimes first observed as 13 failure of conception in the female to whom the male had been bred, or as a painful 14 attempt during a natural breeding. This change in behavior may be the most apparent 15 sign in an otherwise asymptomatic male. A male who historically exhibited normal 16 breeding behavior may become unwilling to mount and gain intromission. An affected 17 male may start scrotal licking to the extent of hair loss and scrotal dermatitis. Multiple 18 etiological agents are possible for such behavior. Only after obtaining a good history, 19 performing a thorough physical examination, and choosing the appropriate diagnostic 20 tests can the underlying reason for a behavioral change, pregnancy failure in bred 21 females, or purulent preputial discharge be determined. Subsequent therapy can then 22 begin which may or may not maintain the male’s potential to be a satisfactory breeder. 23 59 Orchitis and epididymitis can occur separately or in concert since each organ has close 24 anatomical positioning and connection to a common excurrent duct system. 25 Inflammation of one structure can lead to inflammatory response of the other and thus the 26 term orchiepididymitis or epididymo-orchitis is used in veterinary literature.1-4 This 27 condition is rarely found or perhaps diagnosed among tom cats. 28 Anatomy 29 Body weight and breed dimensions should correlate with testicular weight, 30 volume, width and, therefore, quantity of ejaculate. Each testicle is positioned obliquely 31 within the scrotum of the stud dog and tom cat. The head of the epididymis is attached to 32 the cranial aspect of the testis, the body lying on the dorsolateral surface, and the tail 33 fixed to the caudal end by the ligament of the tail of the epididymis or former 34 gubernaculum testis.5 The epididymis continues as the ductus deferens within the 35 spermatic cord, which also encloses the testicular artery and vein, pampiniform plexus, 36 cremaster muscle, and lymphatics. The cord is wrapped on the outside by the visceral 37 vaginal tunic and overlaid by the parietal vaginal tunic as it passes through the inguinal 38 canal. Deep to these two tunics, the testis is also covered by a thick, white, fibrous, 39 tightly adherent capsule called the tunica albuginea. 40 The body of the testis or testicular parenchyma is subdivided into compartments 41 of seminiferous tubules by connective tissue septae. Spermatogenesis occurs within these 42 seminiferous tubules. The sections of tubules feed sperm into a collection of spaces and 43 ducts called the rete testis. A band of connective tissue called the mediastinum testis 44 splits the testicle longitudinally and serves as the entry and exit point for testicular blood 45 60 vessels and lymphatics. From the rete testis, sperm cells then move into and through the 46 head, body and tail of the epididymis where spermatozoal maturation and storage occur. 47 Descent of the testicles into the scrotum occurs in a similar pattern for the dog and 48 tom cat. As the gubernaculum shortens, each testis passes through its respective inguinal 49 canal and ring. When this passage occurs, the testes is already covered by the visceral 50 tunic and then overlaid with the outer or superficial parietal tunic. Completion of this 51 process usually occurs prior to birth in the normal male. However, male cats have been 52 noted to have testicular movement back and forth through the inguinal canal after birth 53 and prior to puberty.6 54 Each testis is partitioned into three sections. The interstitial portion contains the 55 Leydig or interstitial cells, blood vessels and some support tissue. This section functions 56 to provide hormones and nutrition to its respective area. The second or basal 57 compartment is comprised of Sertoli cells and undifferentiated germ cells called 58 spermatogonia. The third and innermost adluminal compartment houses the developing 59 stages of spermatozoa and is separated from the basal section by the immunologically 60 sensitive blood-testis barrier. 61 Etiology 62 Infectious 63 Bacteria enter the testis or epididymis through several routes: from an ascending 64 source through the penile urethra, from descending flora within the adjacent bladder or 65 prostate, and hematogenously. The primary bacterium associated with canine infertility is 66 Brucella canis,7 however other Brucella spp. (eg. Brucella abortus) have been cultured 67 from the epididymis in the canine.8 Additional bacteria are hemolytic E. coli, Proteus 68 61 vulgaris, Staphylococcus spp. as a natural skin contaminant, and Mycoplasma spp.3-9 69 Also the canine distemper virus10 with its cytoplasmic and intranuclear inclusions, 70 granulomatous epididymitis from mycotic Rhodotorula glutinis,11 Blastomyces,12 human 71 tuberculosis,3 Rocky Mountain spotted fever,4 and canine ehrlichiosis (Lyme disease) 72 have been reported as potential causes. The distemper virus is spread venereally to 73 susceptible bitches which acquire an endometritis.3 Mycoplasma canis is a natural 74 component of urogenital and respiratory mucosal surfaces in the dog and cat13 and can 75 cause purulent prostatitis and epididymitis. A bacterial urinary tract infection can incite 76 orchiepididymitis since there is potential for retrograde or reverse urethral pressure 77 through the ductus deferens. Bacterial infections can occur following injuries from 78 pelvic fracture and surgical resection of ileum.3 Unusual reports occur when certain stud 79 dogs still sire litters despite heavy bacterial growth of Klebsiella pneumoniae and 80 Streptococcus after antibiotic treatment for a preliminary diagnosis of epididymitis.14 81 A stray cat that was positive for feline immunodeficiency virus (FIV) and feline 82 leukemia virus (FeLV) had chronic necrotic and fibrinous orchitis.15 Tuberculosis was 83 reported as the cause for a reproductive infection of tom cats in foreign countries.16 84 Brucella spp.7,17,18 and periorchitis from feline infectious peritonitis (FIP) were noted as 85 well. Cats are resistant to infection with Brucella canis.19 86 Testicular injury from a bite wound or puncture results in injection of bacteria or 87 viral particles into the animal, followed by entry into the venous blood and initiation of 88 an inflammatory response. The cellular influx causes swelling and edema of the 89 immediate area. White blood cells are attracted to the site and begin phagocytosis. The 90 increased blood supply soon spreads a local infection systemically. If the animal 91 62 becomes septicemic with bacteria such as hemolytic E. coli, effects of endotoxemia on 92 the kidney impair glomerular filtration rates. As endotoxemia ensues, the animal 93 becomes febrile. A local thermal effect on the ipsilateral testis diminishes 94 spermatogenesis and promotes agglutination of sperm which turns into oligospermia, 95 anesthospermia, or azoospermia. As the condition becomes chronic, testicular atrophy 96 results. Bacterial ascension from proximal prostatic secretions or a urinary tract infection 97 can initiate orchitis and epididymitis. 98 Non-infectious 99 Non-infectious, atraumatic orchitis or epididimytis occurs with the entry of sterile 100 urine through the ductus deferens into the testicle. Blunt force injury to the abdomen, 101 such as happens from an animal being hit by a car, can cause urine to abnormally flow 102 from a full bladder to the testicles.3 103 In humans, even temporary duct blockage secondary to prostatitis can lead to 104 immune-mediated infertility.20 The blood-testis barrier was described in detail by 105 Amann in 1989.21 The blood-testis barrier is comprised of tight junctions between 106 adjacent Sertoli cells resting on the basement membrane. Any breakdown of this barrier, 107 from trauma, infection or an inflammatory response, breaches the immunologically 108 protected status of the testis. This affront allows the immune system to react to the 109 antigenic insult. Sometimes the reaction produces a sperm granuloma at the puncture 110 point. The attraction of plasma cells and lymphocytes into the testicle does produce a 111 residue of immunoglobulins within the seminiferous tubules. The loss of testicular 112 function by the tubules, Leydig cells and impaired vascular flow results in reduced sperm 113 development. Clinically, immune-mediated infertility will be manifested by 114 63 oligospermia or azoospermia. Immune-mediated orchitis can be temporary or 115 permanent.20 116 Similar to that observed in humans, immune-mediated disease has been associated 117 with infertility in the dog. The incidence of lymphocytic orchitis in dogs is correlated 118 with lymphocytic thyroiditis, a heritable trait in Beagles.22,23 Males with this 119 autoimmune disorder had lesions of tubular degeneration, atrophy and lymphocytic 120 orchitis. Therefore, a history of reproductive failure in a stud dog that has been 121 diagnosed with other endocrine diseases should prompt further analysis. 122 Pathophysiology 123 The blood supply to the testes and epididymides comes from the testicular artery 124 and the artery of the ductus deferens, respectively. Both structures are influenced by 125 hormones, both play an important role in spermatogenesis, and both tissues are altered by 126 inflammation and antibody formation. Existing infections within the bladder or prostate 127 gain entry into the ductus deferens by retrograde route. Inflammation from regional 128 lymph nodes reaches the testis or epididymis by lymphatic drainage and then into the 129 blood stream. Epididymal occlusion may appear secondary to an infection. The more 130 proximal the blockage to the adjacent testis, the worse the damage to that testicle.24 131 Viral agents such as feline coronavirus are engulfed by and replicate in 132 macrophages. These macrophages then travel to target organs and mix with lymphocytes 133 to form a fibrin layer on the tunica albuginea (i.e., periorchitis), a finding consistent with 134 FIP.15 Since the parietal and vaginal tunics are continuations of the peritoneal cavity, 135 seeding from a contaminated surgical site or traumatic injury can extend infections into 136 these reproductive organs. Small abscesses within the lumen or testicular parenchyma 137 64 increase in size and extend fistulous tracts through the scrotal wall. Adhesions develop 138 and block tubular patency. Gangrenous inflammation occurs within the unyielding 139 tunics, which inhibit testicular mobility and increase scrotal temperature. Inflammation 140 of the spermatic cord results in vascular compromise, tissue necrosis and eventually 141 testicular atrophy.3 142 The interstitial compartment houses immune cells that maintain the testis in an 143 immunologically secure location. Spermatogonia within this compartment are protected 144 from an autoimmune attack. In addition to the blood-testis barrier, a multitude of factors 145 establish this privileged immune status. Androgens influence the inhibition of 146 proinflammatory cytokines.25 Pro- and anti-inflammatory cytokines regulate testicular 147 function relative to both spermatogenesis and steroidogenesis.26 Pro-inflammatory 148 cytokines such as interleukin and anti-inflammatory cytokines are linked to testicular 149 development.27 Therefore, an insult from infection or trauma induces production of these 150 respective regulatory proteins and likewise disrupts testicular function. Timed 151 progression of focal or diffuse inflammation in testicular tissue eventually results in loss 152 of seminiferous tubules by replacement with connective tissue fibrosis. The clinical 153 outcome of this sequence is manifested as infertility. 154 Another source of immune protection in the testis is the resident population of 155 macrophages. Macrophages assert cytotoxic and phagocytic activity against infection 156 through the cellular inflammatory response.28 For example, Brucella canis embeds itself 157 within macrophages that ultimately seek steroid-dependent organs such as the testis and 158 epididymis.7 These immune and inflammatory components combat and modify normal 159 65 internal testicular functions that correspond to owners’ complaints of nonpregnant 160 matings, scrotal swelling or pain. 161 Clinical signs 162 Historical information provided from the breeder client often supplies the first 163 clue to the diagnosis of orchiepididimytis. Breeder clients are conscientious and notice 164 conception failures. Owners or handlers observe stud dogs not wanting to ejaculate, or an 165 enlarged scrotum while grooming for a show or field trial. The client may report 166 previous urinary or reproductive tract infections, an increased licking of the scrotum, an 167 obscure hindleg lameness, stiff or altered gait, purulent preputial discharge, or palpable 168 unilateral testicular atrophy. All prior medical problems, treatments, hormonal adjuvants 169 and products should be chronologically recorded for review.29 As one source 170 commented, a client’s conclusion may be ‘infertility in an otherwise asymptomatic dog’.2 171 Additional signs include lethargy, anorexia, fever of unknown origin, inappetance, and 172 vomition. Physical findings indicate a swollen scrotum and testicle or epididymis, 173 primarily unilateral enlargement, but it can be bilateral. The testis is asymmetrical; the 174 scrotum is reddened or hyperemic and hyperthermic. The dog licks the area causing a 175 ‘lick’ granuloma or scrotal dermatitis and exhibits a level of discomfort and pain during 176 palpation of the testicles. If the dog resists or is reluctant for digital examination, 177 tranquilization might be necessary. The expression of pain can be acute, episodic and 178 increase with intensity during a natural cover or manual collection. A decrease or loss of 179 libido is evident. One older male had a progressive bilateral alopecia and feminization 180 syndrome associated with acute and chronic epididymitis.30 181 66 Digital palpation may distinguish swelling of the head, body and/or tail of the 182 epididymis and testes. The swollen area often has a soft, doughy texture in acute cases, 183 and a firm, fibrotic consistency in chronic cases. A small puncture wound may be 184 discovered with or without draining purulent exudate or concurrent orchitis. A 185 spermatocoele, sperm granuloma, or hematoma within the tunic linings or in the vaginal 186 cavity may be found. A serosanguineous or purulent discharge from the dog’s preputial 187 orifice may be present. 188 In summary, the typical clinical signs exhibited with prostatitis include a blood-189 tinged ejaculate, hematuria, and difficulty in defecation. Massage of the prostate per 190 rectum may aid in detection of a purulent discharge from the urethra.3 However, like 191 prostatitis, orchioepididymitis can present with similar signs: altered hindlimb gait, 192 lethargy or pain. To help differentiate prostatitis from orchioepididymitis, digital 193 examination would reveal symmetrical or asymmetrical distension of the inflamed 194 prostate. 195 Diagnosis 196 A thorough anamnesis should be recorded. Historical information should include 197 details of prior reproductive attempts, onset and duration of signs and subtle changes in 198 behavior or clinical signs. A chronologically ordered medical history is beneficial. 199 Notations are made of diet, supplements, deworming program, schedule of vaccinations 200 and past medications or surgical therapy. Potentially confounding effects of age, 201 temperament and conformation on behavior or locomotion need to be noted. A physical 202 examination, beginning with a TPR, should conclude with a digital evaluation per rectum 203 of the prostate for size, symmetry, consistency, and pain response. Palpation of each 204 67 testis for size, shape and consistency can often discern a soft, acute onset condition from 205 a firm, nodular chronic problem. Likewise, palpation of the epididimydes can aid in the 206 identification of unilateral or bilateral testicular atrophy based upon the relative 207 prominence of epididymal structures. If severe, acute pain is shown during examination, 208 the primary differential diagnosis is torsion of the spermatic cord. If the scrotum itself is 209 swollen, the examiner then must determine whether it is an intratesticular enlargement or 210 an extratesticular disorder. Ultrasonography would assist in differentiation of the 211 location and tissues involved.31 A swollen scrotum should be distinguished from swollen 212 testes.32 Symmetrical scrotal enlargement occurs in orchitis, hydrocele, and torsion of the 213 spermatic cord. Asymmetrical scrotal shape results from neoplasia, varicocele, 214 epididymitis, abscess, or hematoma. An ultrasound-guided cystocentesis can be 215 performed and urine submitted for cytology and culture. 216 In all cases of orchioepididymitis, a screening test for Brucella canis should be 217 submitted with other samples for clinical pathology. A caution should be issued at that 218 time to client and clinic regarding minimization of potential for human exposure to this 219 zoonotic disease until the results are confirmed. 220 For the breeding soundness evaluation, testicular measurements with a caliper 221 document any change in size or shape. The semen collection should be fractionated into 222 separate samples for determination of sperm motility, morphology, concentration, 223 cytology, culture and sensitivity, and pH. Sperm can also be placed in extender for 224 computerized analysis. In azoospermic samples, an alkaline phosphatase value from 225 seminal plasma of the second fraction would confirm epididymal patency or blockage. In 226 cases of oligospermia or azoospermia, retrograde ejaculation of sperm into the urinary 227 68 bladder can be diagnosed by the presence of spermatozoa in urine obtained post-228 collection.9,23 A stained cytology slide of the third fraction containing ample bacteria 229 and greater than three to five neutrophils per high power field (100X) is diagnostic for 230 prostatitis. Further imaging or follow-up evaluation is indicated. The semen evaluation 231 yields a decreased number of sperm and an increased amount of abnormal morphology 232 from increased agglutination. Bacterial epididymitis causes sperm acrosomal 233 degeneration with subsequent loss of the plasma membrane. Affected sperm cells cannot 234 penetrate the zona pellucida of the oocyte. Infertility results.34 235 Except during the active process of ejaculation and urination, seminal fluid 236 normally moves from the ductus deferens into the bladder.21 The prostatic fluid travels 237 cranially into the bladder by normal urethra pressure.35 Therefore, bacteria from the 238 ductus can produce an ascending prostatic or urinary tract infection (UTI). Culture of a 239 urine sample obtained by cystocentesis would identify the causative bacteria, including 240 the opportunist, Mycoplasma canis, if the specimen is cultured on appropriate media.13 241 Careful manipulation of the scrotum and its contents is useful in the identification 242 of a puncture wound or laceration, a draining tract, a change in skin thickness, altered 243 sensitivity, differentiation of intratesticular or extratesticular origin, or the soft core of an 244 abscess as one sequela of orchioepididymitis. Fibrosis and scrotal adhesions restrict 245 testicular mobility, and with degeneration, the consistency changes from soft, edematous 246 tissue to a firm, hard, smaller and fibrotic testis. 247 Ultrasonography (US) provides a rapid, non-invasive imaging tool beneficial for 248 diagnosis, prognosis and a therapeutic plan.31,36 With US, abnormal testicular 249 architecture can be differentiated from the diffuse, hypoechoic pattern imaged in normal 250 69 testicular parenchyma.37 Fluid in testicular cysts, a spermatocele, or an abscess can also 251 be detected.37 In humans, the most common diagnosis for a swollen, painful scrotum is 252 epididimytis, and it is most commonly diagnosed on ultrasound examination when 253 viewed as increased vascularity in a testis of otherwise normal architecture.38 When a 254 dog presents with an acute onset of scrotal pain and swelling, color flow or power 255 Doppler US imaging can distinguish between the lack of arterial and venous perfusion 256 caused by torsion of the spermatic cord and the hyperemic blood flow from an infectious 257 agent.39,40 Following an incident of testicular torsion, Doppler can visualize disrupted 258 blood flow within the cord and altered echogenicity from testicular infarction. Doppler 259 US is helpful in the localization of a lesion in either the tail of the epididymis, the 260 spermatic cord or tunics, or the testis proper. Neoplasia, either Leydig or Sertoli cell 261 tumors, may have hypoechoic and hyperechoic areas that are usually well-defined.4 262 Testicular tumors have an irregular, lobulated contour versus orchitis with a moderately 263 enlarged, oval shaped, smooth textured testicle.4,39 Tumors of the epididymis are rare.41 264 However, documentation in human cases is more widely reported. 265 One author suggested using fine-needle aspiration (FNA) from the caudae 266 epididymides to collect diagnostic samples under sterile conditions from infertile males 267 for cytology, histopathology, culture (aerobic, anaerobic, and Mycoplasma).42 Fine-268 needle aspiration has been used to confirm obstructive lesion or maturation arrest for 269 oligospermia and azoospermia.43 Ultrasonography can select which patient would 270 benefit from this procedure and avoid inherent risk or immunological consequences.36 271 The accuracy and placement of the needle can be improved through ultrasound guidance 272 as well. While a FNA sample for a cytology smear is presumptive for diseases such as 273 70 lymphocytic orchitis, a testicular slice biopsy will confirm the diagnosis. It may be 274 advisable to weigh the short-term benefit versus the long-term risk since adverse effects 275 may develop later. Focal hemorrhage, interstitial fibrosis and tubular atrophy can occur 276 at a biopsy site, but adjacent tissue and semen quality may remain within normal 277 limits.44,45 With either method, there is risk for sperm granuloma formation or antisperm 278 antibody production as a result of ‘foreign’ protein leaking from the point of surgical 279 extraction through tunics, cavity, parenchyma and blood-testis barrier. One would 280 obviously not perform a testicular biopsy or risk anesthesia in the presence of 281 inflammation.2 282 Prostatic disease can be verified by anamnesis, digital examination, culture and 283 sensitivity, cytology of the third fraction or prostatic wash, ultrasonography, and 284 ultrasound-guided aspirate or biopsy. 285 If an orchidectomy of a diseased testis is performed, samples obtained at surgery 286 should be cultured for aerobic bacteria, Mycoplasma spp. and fungi, and tissues should be 287 sent for histopathology. 288 Pathology 289 Epididymitis is one of the more common inflammatory diseases of the 290 reproductive tract. The usual route of entry for pathogens into the epididymis is via an 291 ascending or retrograde mechanism. Trauma to the scrotum combined with endotoxin-292 producing bacteria such E. coli results in septicemia. The epididymis lacks a natural 293 local immune system. Lymphocytes or plasma cells are recruited after the initial insult 294 from infection occurs. Edema progresses to an abscess or sperm granuloma formation. 295 Fibrous bands appear between the tunics, which are extensions of the peritoneal cavity,3 296 71 and the epididymis. In time, these adhesions lead to testicular atrophy and firm, nodular 297 ducts. Scrotal swelling is caused by the accumulation of fibrinopurulent exudate in the 298 tunic cavity. This cellular response includes lymphocytes, neutrophils and macrophages. 299 Extensive luminal fibrosis and spermatocele can occlude the ducts even after successful 300 treatment and decreased signs of inflammation. Disruption of the blood-testis barrier 301 initiates an immune-mediated reaction and results in lymphocytic infiltration. 302 Inflammation of the seminiferous tubules causes degeneration. The inflammatory 303 response within the testicular parenchyma is suppurative, with abscessation and possible 304 fistula formation to the exterior scrotum.17 Lesions in a cat with orchitis were consistent 305 with vasculitis, increased fibrinogen and infarction from simultaneous viral infections.15 306 Multifocal necrotic granulomatous inflammation of the pleura, lung, eye and lip were 307 found. 308 Treatment 309 Similar treatment protocols are suggested for both orchitis and/or epididymitis. 310 Once the cause is known, an appropriate regimen can be instituted. Antimicrobial 311 therapy is started based upon results of the culture and sensitivity. A minimum duration 312 of treatment is three to four weeks. Concurrent sexual rest is implied. Another culture 313 should be obtained one to two weeks after the antibiotic has been discontinued. 314 Resolution of epididymitis requires the correct antimicrobial choice, dosage and length of 315 administration. Too often, failure of client compliance alters the outcome when treatment 316 is stopped prematurely. Within days, owners may supplement with their choice of 317 medication in addition to or in place of the one prescribed. Immunosuppressive drugs 318 have been used on a short-term basis to treat immune-mediated disease. However, 319 72 continued use of immuosuppressive agents may adversely affect spermatogenesis and 320 lead to infertility. 321 Owners should be apprised of possible outcomes and expense. Serial monitoring 322 can document changes in semen parameters and allow for alteration of therapy if 323 necessary. Brucellosis management requires immediate quarantine and testing of dogs 324 having had contact with the confirmed case. Positive dogs are removed from the 325 premises and are either euthanized or retested until two negative results have been 326 obtained. Antibiotics will decrease bacteremic signs and neutering does eliminate the 327 target organs, but the chance for relapse is probable. Since brucellosis is zoonotic, 328 exposure to pregnant women, children and immunosuppressed people, in particular, 329 should be avoided. Treatment for unilateral epididymitis offers a better recovery rate; 330 bilateral infection has a poorer prognosis for a return to satisfactory reproductive 331 performance.23 332 The treatment of choice may be surgical excision of the infected tissue. Relief is 333 immediate and the potential for fertility may be salvaged. Hemicastration or 334 orchidectomy of the diseased testis not only removes the source of inflammation or 335 benign neoplasia but also decreases the potential for thermal insult on the unaffected, 336 contralateral testis. Following unilateral orchidectomy, an immediate reduction in sperm 337 output was followed by increased spermatogenesis and compensatory hypertrophy by the 338 remaining testis.46 If the preliminary histopathology confirms malignancy or an 339 irreversible condition, complete castration may be recommended for the animal’s 340 welfare. If the cause can be reversed, then the male may recoup fertility. If the primary 341 problem is torsion of the spermatic cord, an infectious disease or immune-mediated 342 73 disorder which resulted in secondary damage, any resolution of pre-existing 343 orchioepididymitis may be irrelevant. The progressive fibrosis within the tubular 344 compartments would gradually prevent spermatogenesis and steroidogenesis. 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