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Distribution of histopathology and Ia positive cells in actively induced and passively transferred experimental autoimmune orchitis.

Histopathology in testes from mice with actively induced experimental orchitis (EAO) (active EAO) and those from recipients of testis-sensitized lymphocytes (passive EAO) had different distributions. In passive EAO, maximum orchitis existed in the straight tubules, rete testis, and ductus efferentes, obstruction of which led to extreme dilatation of seminiferous tubules. Unusual intralymphatic granulomata also resulted in dilated testicular lymphatics. In active EAO, maximum orchitis affected seminiferous tubules under the testicular capsule, away from the rete testes. Vasitis was common and occurred in both active and passive EAO. In normal testes, IA+ F4/80+ cells were sparse but formed a cuff around the straight tubules. After immunization with testis in adjuvant or with adjuvant alone, the number, size, and staining intensity of IA+ cells increased dramatically beginning on day 5, 7 days before disease onset. Simultaneously, epithelial cells confined to the ductus efferentes became Ia+. Although recipients of sensitized lymphocytes also developed epithelial Ia in the ductus efferentes, they did not show changes in testicular interstitial Ia+ cells. Our findings indicate that testicular autoantigens are not completely sequestered, but are accessible to and can react with passively transferred immune lymphocytes in well-defined regions of the germ cell compartment. These regions coincided to a large extent with maximum expression of periductal or epithelial Ia. Changes in Ia+ cells in the testis, which are inducible by adjuvants and precede orchitis, may account in part for the different distribution of histopathology of active EAO.

Animals↗

[Infertility after mumps orchitis (author's transl)].

Mumps orchitis is the most frequent complication of mumps in young men. 11 of 23 patients were followed up, 9 answered a questionnaire. 11 spermiograms were available. 6 patients, 3 of them after bilateral mumps orchitis, had children. Although some severe fertility disturbances were seen, no case of real infertility was found. The rate of atrophy was 53%. 12 patients remained at least subfertile (60%), 5 of them after bilateral mumps orchitis, 3 patients were almost infertile after bilateral mumps orchitis. Patients with corticosteroid therapy showed better results at followup examinations than the others, although no significance was found (alpha greater than 0.05).

Adolescent↗

[Asymptomatic synchronous bilateral granulomatous orchitis--a case report].

A case of asymptomatic synchronous bilateral granulomatous orchitis in a 79-year-old male patient is described. He was diagnosed with asymptomatic microhematuria, and referred to our outpatient clinic. In the physiological examination, there were stone-hard indurations in his bilateral testes. There were multiple hypoechoic areas in the scrotal ultrasonography. Bilateral testicular tumor was suspected. However, histological findings after bilateral orchidectomy revealed granulomatous orchitis. Abdominal computed tomography revealed swelling of the paraaortic lymph nodes postoperatively. However no malignant origin was detected. Differential diagnosis between testicular tumor and granulomatous orchitis is very difficult in any examination except by histological findings. Conservative therapy is usually not effective, and most cases are treated by orchidectomy. Bilateral cases of this entity are relatively rare, but in young cases, it is necessary to distinguish the granulomatous orchitis from the testicular tumor before surgical intervention.

Aged↗

[Brucella orchitis].

Brucellosis is a multi-organ infectious disease which affects the genito-urinary system in 2-10% of cases, mainly as orchitis. There have been very few reports in Israel of genito-urinary system involvement in patients with brucellosis, possible due to a low index of suspicion. Identification of brucella orchitis would result in proper medical treatment, thus preventing unnecessary surgery. We present a case of brucella orchitis, highlighting the place of brucellosis in the differential diagnosis of orchitis.

Adult↗

[Syphilitic orchitis: report of a case].

Syphilitic orchitis ir recently a rare disease in Japan. A 44-year-old man visited our hospital with the complaint of swelling of the right scrotum. He first noticed it about a half year ago, but the swelling mitigated without any therapy. The right testis was about the size of a hen's egg, elastic hard, and slightly rugged when he first visited our hospital. Treponema pallidum hemagglutination assay (TPHA) and rapid plasma reagin (RPR) were positive. We performed high orchiectomy because we could not deny the possibility of testicular tumor. Pathologically, granulomatous inflammation with lympho-plasmacytic infiltration and endoarteritis obliterans of the small arteries were seen in the specimen. It was diagnosed as granulomatous inflammation possibly caused by syphilitic orchitis. Syphilitic orchitis is usually quite difficult to distinguish from other types of granulomatous diseases of the testes, for example tuberculous orchitis. Various types of stains and careful examination of the specimen were thought to be necessary to distinguish these diseases.

Adult↗

Autoimmune orchitis, epididymitis, and vasitis are immunogenetically distinct lesions.

Experimental allergic orchitis (EAO), the principle animal model of noninfectious testicular inflammatory disease, is a genetically determined phenotype. Classical EAO, induced by inoculation with testicular homogenate and the appropriate adjuvants, is characterized by inflammatory infiltrates in the testis (orchitis), epididymis (epididymitis), and vas deferens (vasitis). In this study, the genetic control of susceptibility and resistance to these three lesions was analyzed in the mouse. The results obtained with independent inbred strains and H2 congenic mice show that the genetic control of all three lesions is complex and involves both H2 and non-H2-linked genes. Whole-genome exclusion mapping was performed on a backcross population segregating for all three phenotypes. Permutation-derived thresholds provided experimentwise, chromosomewise, comparisonwise, and marker-specific chromosomewise thresholds for declaration of significant regions linked to marker loci. Unique loci were identified on chromosome 8 for orchitis, chromosome 16 for epididymitis, and chromosome 1 for vasitis and have been designated as Orch6, Epd1, and Vas1, respectively. These results show that autoimmune orchitis, epididymitis, and vasitis are immunogenetically distinct lesions.

Animals↗

[Mumps orchitis; review of 8 cases].

OBJECTIVE: To determine the incidence of mumps orchitis in young males in the area of El Bierzo (Ponferrada, Spain) and the complications arising from this condition. METHODS: The cases of mumps orchitis referred by the primary care services to the emergency services of Hospital del Bierzo referral center were reviewed. We analyzed patient age, unilateral or bilateral testicular involvement, whether the patients had been vaccinated against mumps and the changes observed in the semen analysis. RESULTS: The diagnosis of mumps orchitis was confirmed in 8 patients, aged 15 to 19 years. Two patients had bilateral testicular involvement. Seven patients had not been vaccinated against parotiditis. Three patients had oligoasthenospermia and are currently being followed at the Urology services. CONCLUSIONS: The utility of large scale vaccination against mumps is emphasized. Long-term follow-up is recommended for all patients with abnormal semen analysis, particularly those with bilateral testicular involvement, since they may develop oligoasthernospermia several years after the infection or improve with item. A high incidence of mumps orchitis was found for this 12-month study period.

Adolescent↗

An evaluation of the role of the intravenous urogram in the management of patients with epididymo-orchitis.

The purpose of this study was to evaluate the role of intravenous urography in patients presenting with symptoms of epididymo-orchitis. The intravenous urograms of 67 such patients were assessed retrospectively. The management of patients with acute epididymo-orchitis was not affected by intravenous urography, although a number of abnormalities were identified. Patients with additional symptoms not typical of acute epididymo-orchitis showed a higher incidence of abnormalities some of which affected management. It is concluded that urography is not warranted in the investigation of patients with uncomplicated acute epididymo-orchitis.

Epididymitis↗

[Systemic alpha-interferon therapy: a possible method for prevention of testicular atrophy and permanent sterility in patients with bilateral mumps orchitis].

In postpubertal men orchitis is the most common complication of mumps infection, occurring in 5-37% of this population. A bilateral manifestation is observed in 16-65%. The most important danger is the risk of developing testicular atrophy, which results in sterility. Four patients with bilateral mumps orchitis received systemic treatment with interferon-alpha 2B (3 X 10(6) IU/day) for 7 days. All acute symptoms of mumps orchitis disappeared within 2 or 4 days of hospitalization. During 12-20 months of follow-up no incidence of testicular atrophy was observed. In three of the four patients pretreatment examination revealed subfertility (oligoasthenozoospermia), while 2-4 months after interferon treatment and throughout the entire follow-up period normozoospermia was found. No severe adverse effects occurred during treatment. The flu-like symptoms could be prevented by concomitant administration of paracetamol (3 X 500 mg/day). Systemic treatment with interferon-alpha 2B appears to be highly effective in preventing sterility and testicular atrophy after bilateral mumps orchitis. Further investigations involving larger populations should be performed to confirm the present promising results.

Adult↗

Ruling out pediatric bacterial epididymo-orchitis with urinalysis - The case for minimizing unnecessary antibiotic prescription.

INTRODUCTION: Epididymo-orchitis in pediatric patients is predominantly non-bacterial, often stemming from viral or reactive etiologies. Despite guidelines recommending conservative management for non-bacterial cases, antibiotic overtreatment remains prevalent in the outpatient setting. We evaluated the diagnostic accuracy of urinalysis in ruling out bacterial infection to support antibiotic stewardship in this population. METHODS: We conducted a cross-sectional diagnostic accuracy study using electronic health records from a large health maintenance organization in Israel. The cohort included patients younger than 18 years with a diagnosis of epididymo-orchitis or clinically overlapping entities (acute scrotum, appendage torsion) who had paired urinalysis and urine culture results within one week of diagnosis. Logistic regression and ROC curve analysis were performed to assess the ability of urinalysis parameters to predict positive urine cultures. RESULTS: Of 682 eligible cases, confirmed bacterial infection was rare, occurring in only 17 patients (2.5%). Nitrite positivity was the strongest independent predictor of infection (OR 43.98; p < 0.001). A prediction model incorporating all urinalysis parameters yielded an area under the curve (AUC) of 0.825 and achieved a 97.7% classification accuracy for correctly predicting negative cultures. Despite the low prevalence of infection, antibiotics were prescribed in 237 cases (34.7%). Urinary anatomic abnormalities were significantly associated with culture positivity. CONCLUSIONS: Bacterial coinfection in pediatric epididymo-orchitis is uncommon. Urinalysis serves as a highly accurate screening tool to rule out bacterial etiology. A negative urinalysis supports withholding antibiotics in this setting, reserving treatment for children with positive markers or known anatomic abnormalities. This evidence-based approach This evidence-based approach has the potential to reduce unnecessary antibiotic exposure, however prospective studies are needed to validate these findings before broad implementation.

Humans↗

Sonographic findings in tuberculous epididymitis and epididymo-orchitis.

PURPOSE: This paper presents the sonographic findings in scrotums of patients affected with tuberculous epididymitis or epididymo-orchitis. METHODS: Eighteen patients with a total of 22 abnormal hemiscrotums (4 patients had bilateral lesions) underwent scrotal sonography. Pathologic confirmation was obtained via epididymectomy in 10 cases, epididymo-orchiectomy in 7 cases, and scrotal exploration and biopsy in 3 cases. The histopathologic diagnosis was tuberculous epididymitis in 12 cases and epididymo-orchitis in 8 cases. RESULTS: Lesions involved the head of the epididymis in 8 cases, the tail in 5 cases, and the entire epididymis in 9 cases. The enlarged epididymis was hypoechoic in 13 cases, hyperechoic in 2 cases, and of mixed echogenicity in 7 cases. The echotexture was heterogeneous in 17 cases and homogeneous in 5 cases. Testicular involvement in 7 cases appeared as a diffusely enlarged hypoechoic testis in 2 cases, an ill-defined hypoechoic lesion in 1 case, a well-demarcated hypoechoic lesion in 2 cases, and multiple small hypoechoic nodules in an enlarged testis in 2 cases. Hydrocele, sinus tract, and extratesticular calcifications were seen in 12, 4, and 2 cases, respectively. CONCLUSIONS: The heterogeneous and hypoechoic swelling of the epididymis or the concomitant hypoechoic lesion of the testis with associated sinus tract or extratesticular calcifications may be helpful in the diagnosis of tuberculous epididymitis or epididymo-orchitis, especially in patients with known genitourinary tuberculosis.

Adolescent↗

Diagnosis of isolated tuberculous orchitis by fine-needle aspiration cytology.

An isolated tuberculous Orchitis without epididymal involvement is rare. This case report describes an extra pulmonary tuberculosis with exclusively testicular presentation. The confirmatory diagnosis of which was made on FNAC of the testis. A 22-year-old adult presented with unilateral testicular enlargement and scrotal ulcer on the same side. FNAC was performed and subsequent smear examination revealed epitheloid granuloma in a necrotic background. This was suggestive of tubercular orchitis, which was further confirmed by demonstration of very occasional acid fast bacilli in the smear. Isolated tuberculous orchitis is a rare entity; FNAC is a useful first choice of investigation. It provides a successful diagnosis thereby preventing unnecessary orchidectomy.

Adult↗

Mumps epididymo-orchitis with prolonged detection of virus in semen and the development of anti-sperm antibodies.

Epididymo-orchitis is the most common complication of mumps in post-pubertal men. A case of MMR vaccine failure, in whom mumps and mumps-associated unilateral epididymo-orchitis developed, is presented in this article. Mumps virus was isolated from the semen 14 days after onset and mumps RNA was detected in semen for up to 40 days using RT-PCR. Epididymo-orchitis was associated with transient but significant reduction in sperm count and severe abnormalities in sperm morphology. It also led to the appearance of anti-sperm antibodies, which may have potential long-term adverse effects on the patient's fertility. Sequencing of the SH gene of the virus showed this to be a new mumps genotype distinct from the virus circulating currently in the UK.

Adolescent↗

Experimental allergic orchitis in mice. VI. Recombinations within the H-2S/H-2D interval define the map position of the H-2-associated locus controlling disease susceptibility.

Susceptibility to autoimmune orchitis is associated with an immune response (Ir) gene (now designated Orch-1) which was preliminarily shown to reside at or near the H-2D subregion of the major histocompatibility complex in the mouse (H-2). In this study, the role of H-2 in controlling both disease susceptibility and the phenotypic expression of infertility associated with autoimmune orchitis has been significantly extended. Of nine C57BL/10SnJ and three BALB/cAnN H-2 congenic strains, only those mice possessing the H-2d, H-2p haplotypes exhibited autoimmune orchitis accompanied by infertility. All other congenic strains, including those expressing the H-2 haplotypes v, q, b, s, r, f, and k were of the low responder phenotype. In addition, disease susceptibility was found to be inherited as a dominant trait in H-2 congenic F1 hybrid mice. In order to map the precise location of the Orch-1 locus within H-2, 32 intra-H-2 recombinant congenic strains possessing defined crossovers in various locations throughout the H-2 region were studied. The results of the analysis indicate that Orch-1 maps within the interval between the H-2S and H-2D regions. Our results also indicate that class II genes, i.e., A and E region-encoded genes, have little discernable effect in controlling disease susceptibility and resistance despite the fact that testicular lesions can be adoptively transferred with Ia-restricted CD4+ effector T cells. A comparison of the Orch-1 alleles with the genotypes of two additional markers which map within the H-2S/H-2D interval suggests the following gene order: H-2S--TNP-Ficoll--Orch-1--Tnfa--H-2D.

Alleles↗

Testicular blood flow in experimental torsion and epididymo-orchitis measured by 133Xe clearance technique in rabbits.

Testicular blood flow was measured by intratesticular injection of 133Xe both under control conditions and in experimental 720 degree intravaginal torsion (10 rabbits) and in epididymo-orchitis (5 rabbits). The results were statistically compared with each other. The blood flow was 35.8 +/- 13.7 ml/100 g/min to the right testis and 35.4 +/- 12.7 ml/100 g/min to the left testis under control conditions. The blood flow decreased to 16% and 8% of the control values 1 h and 8 h after torsion respectively. In epididymo-orchitis testicular blood flow stayed within normal limits. There was a significant difference in blood flow between the torsion and epididymo-orchitis groups (p less than 0.001). Further investigation in man will demonstrate whether the 133Xe clearance method can be used in the differential diagnosis of these two pathologies.

Animals↗

Experimental allergic orchitis in mice. II. Association of disease susceptibility with the locus controlling Bordetella pertussis-induced sensitivity to histamine.

Susceptibility to the induction of murine autoimmune orchitis was found to be associated with the locus controlling Bordetella pertussis-induced sensitivity to the vasoactive amine, histamine. Only those inbred and H-2 congenic strains of mice possessing both the H-2d haplotype and the locus for susceptibility to B. pertussis-induced sensitivity to histamine developed autoimmune orchitis. In addition, segregation analysis of backcross generation mice also demonstrated a high degree of correlation between susceptibility both to disease and to histamine sensitization, which was indicative of additional multigene control. Pertussigen-histamine sensitization factor (P-HSF) was only effective in eliciting disease when it was administered on the same day, or within a period up to 6 days following sensitization with mouse testicular homogenate-emulsified in complete Freund's adjuvant. P-HSF induced sensitivity to histamine was not found to be associated with an increase in the vascular permeability of target tissue. Thus, B. pertussis-induced sensitivity to histamine appears to play a more crucial role during the sensitization phase of autoimmune orchitis induction, rather than at the inflammatory or effector phase of the disease.

Animals↗

Experimental allergic orchitis in mice. V. Resistance to actively induced disease in BALB/cJ substrain mice is mediated by CD4+ T cells.

Previous studies have shown that differential susceptibility to actively induced experimental allergic orchitis (EAO) exists among various BALB/c substrains. Of 13 substrains studied, BALB/cJ mice consistently exhibit greater resistance to disease induction. Such resistance is associated with a single recessive genotypic difference in an immunoregulatory locus which is unlinked to any of the known alleles distinguishing the BALB/cJ substrain. In this study, gene complementation protocols were used to study the genetics of susceptibility and resistance to EAO. The results indicate that resistance in BALB/cJ mice is not due to a mutation in the H-2Dd linked gene which governs the phenotypic expression of autoimmune orchitis. The mechanistic basis for disease resistance was examined using reciprocal bone marrow radiation chimeras generated between the disease-susceptible BALB/cByJ (ByJ) substrain and BALB/cJ (Jax) mice. All constructs, including Jax----Jax and Jax----ByJ, developed severe EAO following inoculation with mouse testicular homogenate (MTH) and adjuvants whereas control chimeras immunized with adjuvants alone did not. These results suggest that an active immunoregulatory mechanism rather than a passive one, such as the lack of T cells and/or B cells with receptors for the aspermatogenic autoantigens relevant in the induction of EAO, is responsible for disease resistance in BALB/cJ mice. The role of immunoregulatory cells was examined by pretreating BALB/cJ mice with either cyclophosphamide (20 mg/kg) or low-dose whole body or total lymphoid irradiation (350 rads) 2 days prior to inoculation. BALB/cJ mice immunized with MTH plus adjuvants generate immunoregulatory spleen cells (SpCs) that, when transferred to naive BALB/cByJ recipients, significantly reduce the severity of autoimmune orchitis observed during actively induced EAO. Treatment of such cells with either cytotoxic monoclonal anti-Thy-1.2 or anti-CD4 plus C' before transfer abrogates the ability of BALB/cJ spleen cells to inhibit disease. In contrast, neither SpCs from adjuvant-immunized BALB/cJ nor MTH plus adjuvant-primed BALB/cByJ donors significantly influenced the severity of disease observed in recipients. Taken together, these results suggest that genetically controlled resistance to EAO in BALB/cJ mice is associated with a mutation in an immunoregulatory locus whose effects appear to be mediated through a cyclophosphamide and low-dose radiation-sensitive CD4+ T-cell population.

Animals↗

Acute experimental unilateral orchitis in the rabbit and its effect on fertility.

We examined the nature of contralateral damage following unilateral orchitis to see if an immunologically mediated mechanism was present. Experimentally induced orchitis in 18 white New Zealand rabbits were examined and compared to 20 in the control groups. Serum antisperm antibody presence and bilateral testicular biopsies (Johansen biopsy score, mean seminiferous tubule diameter) were examined and pregnancy rates were noted. Acute orchitis seemed to be a causative factor in production of antisperm antibody and the presence of antisperm antibody caused histologic changes in contralateral testicles and therefore impaired fertility.

Acute Disease↗