Zapalenie najądrza – Patofizjologia i mechanizm

Zapalenie najądrza
Patofizjologia i mechanizm

Zapalenie najądrza (epididymitis) to zapalny stan najądrza, najczęściej o etiologii bakteryjnej, zróżnicowanej w zależności od wieku pacjenta. U mężczyzn <35 roku życia dominują zakażenia przenoszone drogą płciową, głównie Chlamydia trachomatis i Neisseria gonorrhoeae, natomiast u starszych (>35 lat) przeważają infekcje dróg moczowych wywołane bakteriami jelitowymi (Escherichia coli, Klebsiella pneumoniae, Proteus spp., Pseudomonas aeruginosa), często w kontekście przeszkody podpęcherzowej, np. przerostu gruczołu krokowego. Patogeneza opiera się na wstecznym przepływie zakażonego moczu lub patogenów przez układ moczowo-płciowy do najądrza, co może być indukowane przez czynniki mechaniczne (np. manewr Valsalvy, intensywny wysiłek). W niektórych przypadkach zapalenie ma charakter aseptyczny, wywołany np. przez wsteczny przepływ sterylnego moczu, leki (amiodaron), urazy lub choroby autoimmunologiczne (sarkoidoza, zespół Behçeta). Występują także odmienne mechanizmy u pacjentów z wadami odbytu czy urazem rdzenia kręgowego.

Patogeneza Zapalenia Najądrza

Zapalenie najądrza (epididymitis) to stan zapalny najądrza, małej, spiralnie zwiniętej struktury zlokalizowanej na tylnej powierzchni jądra, odpowiedzialnej za magazynowanie i transport plemników. Patogeneza tego schorzenia jest złożona i obejmuje różne mechanizmy zapalne i infekcyjne.¹²

Zakażenia bakteryjne jako główna przyczyna

Większość przypadków zapalenia najądrza ma podłoże infekcyjne, najczęściej bakteryjne. Bakterie mogą dotrzeć do najądrza różnymi drogami, przy czym najczęstszy jest wsteczny przepływ patogenów przez układ moczowo-płciowy.¹²

Zakażenia przenoszone drogą płciową (STI) – u młodych, aktywnych seksualnie mężczyzn (poniżej 35 roku życia) dominującą przyczyną zapalenia najądrza są choroby przenoszone drogą płciową, zwłaszcza zakażenia Chlamydia trachomatis i Neisseria gonorrhoeae. Infekcja początkowo rozwija się w cewce moczowej, a następnie bakterie migrują wstecznie przez nasieniowód do najądrza.¹²
Infekcje dróg moczowych – u mężczyzn powyżej 35 roku życia, zapalenie najądrza najczęściej wynika z wstecznego przepływu zakażonego moczu do najądrza. Podstawowymi patogenami są bakterie jelitowe, w tym Escherichia coli, Klebsiella pneumoniae, Proteus spp. i Pseudomonas aeruginosa. Często występuje to w kontekście przeszkody podpęcherzowej, zwykle związanej z przerostem gruczołu krokowego.¹²

Mechanizm wstecznego przepływu

Główny mechanizm patogenetyczny zapalenia najądrza związany jest z wstecznym przepływem patogenów lub moczu do najądrza.¹

Wsteczny przepływ zakażonego moczu – u starszych mężczyzn z objawami utrudnienia odpływu moczu (np. z powodu łagodnego przerostu prostaty), może dochodzić do wstecznego przepływu zakażonego moczu przez przewód wytryskowy do nasieniowodu i najądrza.¹²
Normalnie ukośne ułożenie przewodów wytryskowych przez gęstą tkankę prostaty zapobiega refluksowi, jednak w przypadku przeszkody podpęcherzowej, ten mechanizm ochronny może być upośledzony.¹
Refleks może być również indukowany przez manewry Valsalvy lub intensywny wysiłek fizyczny. Można to zaobserwować u sportowców, takich jak ciężarowcy. Zapalenie najądrza często rozwija się podczas intensywnego wysiłku w połączeniu z pełnym pęcherzem.¹²

Zapalenie z przyczyn nieinfekcyjnych

Zapalenie najądrza może również wystąpić bez obecności infekcji bakteryjnej:¹

Wsteczny przepływ sterylnego moczu – chemiczne podrażnienie najądrza może wystąpić, gdy sterylny mocz cofa się do najądrza, co może być spowodowane np. dźwiganiem ciężarów.¹²
Leki – niektóre leki, zwłaszcza amiodaron, mogą kumulować się w najądrzu powodując stan zapalny. Występowanie zapalenia najądrza wydaje się być związane z dawką leku.¹²
Urazy – obrażenia okolicy pachwinowej mogą powodować zapalenie najądrza.¹
Choroby układowe – rzadko zapalenie najądrza może być związane z chorobami autoimmunologicznymi, takimi jak sarkoidoza czy zespół Behçeta.¹²

Patogeneza w różnych grupach wiekowych

Etiologia zapalenia najądrza różni się znacząco w zależności od wieku pacjenta:¹

U chłopców poniżej 14 roku życia – przyczyna jest w dużej mierze nieznana, ale może być związana z anomaliami anatomicznymi powodującymi refluks zakażonego lub sterylnego moczu do przewodów wytryskowych. Badania sugerują, że w tej grupie wiekowej zapalenie najądrza jest głównie poinfekcyjną reakcją zapalną na patogeny takie jak Mycoplasma pneumoniae, enterowirusy czy adenowirusy.¹²
U mężczyzn w wieku 14-35 lat – dominują zakażenia przenoszone drogą płciową, zwłaszcza Chlamydia trachomatis i Neisseria gonorrhoeae.¹
U mężczyzn powyżej 35 roku życia – najczęstszą przyczyną jest zakażenie dróg moczowych bakteriami jelitowymi, często w kontekście przeszkody podpęcherzowej.¹²

Szczególne mechanizmy patogenetyczne

Różnice w odpowiedzi immunologicznej w obrębie najądrza

Badania wykazały, że istnieją różnice w ekspresji komórek odpornościowych, genów immunoregulacyjnych i cząsteczek wykrywających patogeny wzdłuż najądrza:¹²

Środowisko tolerogenne istnieje w głowie najądrza (caput epididymidis), co może być związane z potrzebą ochrony neoantygenów plemników wychodzących z jądra.¹
Odpowiedzi zapalne są najbardziej intensywne w kierunku ogona najądrza (cauda epididymidis), co jest zgodne z potrzebą reagowania na wstępujące infekcje.¹²
Zróżnicowana ekspresja genów immunoregulacyjnych, w tym IDO i aktywiny A, oraz mechanizmów wykrywania patogenów, takich jak receptory Toll-podobne (TLR), wzdłuż przewodu najądrza prowadzi do środowiska, w którym odpowiedzi tolerogenne są bardziej preferowane w regionach proksymalnych do jądra, podczas gdy swoista immunologicznie odpowiedź i reakcje zapalne są najbardziej intensywne w ogonie najądrza.¹

Infekcje wirusowe i nietypowe

Oprócz typowych zakażeń bakteryjnych, zapalenie najądrza może być spowodowane przez inne patogeny:¹

Wirus świnki (mumps virus) – ma predyspozycję do infekowania jądra, co może prowadzić do zapalenia jądra i najądrza. Ciężkie przypadki świnki mogą powodować zmniejszenie płodności lub nawet prowadzić do niepłodności.¹²
Mycobacterium tuberculosis – rzadko zapalenie najądrza może być spowodowane przez gruźlicę. Jest to istotne u pacjentów z grupy wysokiego ryzyka.¹²
Inne patogeny – mniej powszechnie związane z zapaleniem najądrza obejmują Ureaplasma urealyticum, Proteus mirabilis, Klebsiella pneumoniae i Pseudomonas aeruginosa.¹

Powikłania i skutki długoterminowe

Zapalenie najądrza może prowadzić do różnych powikłań i długoterminowych konsekwencji:¹²

Niedrożność przewodów – długoterminowe problemy wynikające z zapalenia najądrza u pacjentów są bardzo prawdopodobnie związane z nieodwracalnym rozwojem niedrożności przewodów i przebudową tkanki włóknistej, która występuje pomimo leczenia antybiotykami i eliminacji bakterii.¹²
Włóknienie okołokanalikowe może się rozwinąć, powodując niedrożność przewodów.¹
Niepłodność – w rzadkich przypadkach zapalenie najądrza może powodować niepłodność. Nawet gdy zidentyfikowano przyczynowy organizm infekcyjny i zastosowano odpowiednie leczenie przeciwdrobnoustrojowe, rokowanie dotyczące zachowania płodności u pacjentów z infekcyjnym zapaleniem najądrza jest niepewne.¹²
Martwica tkanki jądra – może wystąpić, gdy jądro nie otrzymuje wystarczającego przepływu krwi. Martwica jądra to rzadka manifestacja zapalenia najądrza w izbie przyjęć, z szacowaną częstością występowania 12% wszystkich przypadków zapalenia najądrza.¹²

Mechanizm martwicy jądrowej w zapaleniu najądrza

Martwica jądra jest spowodowana niedrożnością żylną z jąder. Mechanizm tej parainfekcyjnej zakrzepicy nie jest do końca jasny. Sugerowane mechanizmy przyczyniające się do tej martwicy jąder mogą obejmować:¹

Ucisk żylny przez obrzęk najądrza
Obrzęk powrózka nasiennego w przypadku zapalenia powrózka nasiennego
Obrzęk w zewnętrznym pierścieniu pachwinowym
Toksyny bakteryjne mogą uszkadzać komórki śródbłonka prowadząc do zakrzepicy naczyniowej¹

Zapalenie najądrza w specyficznych populacjach

Zapalenie najądrza może mieć szczególne mechanizmy patogenetyczne w określonych populacjach pacjentów:¹

Pacjenci z wadami odbytu (ARM) – zapalenie najądrza reprezentuje unikalny problem, ponieważ w przeciwieństwie do populacji ogólnej, często identyfikuje się podstawowy problem układu moczowego. Patofizjologia dysfunkcji oddawania moczu może prowadzić do dyssynergii zewnętrznego zwieracza cewki moczowej podczas oddawania moczu, powodując podwyższone ciśnienie cewki moczowej i następnie wsteczny refluks cewkowo-nasiennikowodowy z zapaleniem i bólem.¹
Pacjenci z urazem rdzenia kręgowego – pacjenci ze skurczem mięśniowym mają zmniejszone ryzyko zapalenia najądrza. Skurcz mięśniowy obejmuje skurcz mięśnia wypieracza, zewnętrznego zwieracza cewki moczowej i skurcz mięśni kończyn dolnych. Mechanizm ochronny skurczu przed zapaleniem najądrza można wyjaśnić faktem, że pacjenci z wiotkim pęcherzem mają bezobjawowe, przedłużone zakażenie układu moczowego.¹

Specyficzne przypadki zapalenia najądrza

Przewlekłe zapalenie najądrza

Etiologia przewlekłego zapalenia najądrza obejmuje:¹

Nieadekwatne leczenie ostrego zapalenia najądrza
Nawracające zapalenie najądrza
Związek z reakcją ziarniniakową (najczęściej Mycobacterium tuberculosis)
Skojarzenie z przewlekłym procesem chorobowym, takim jak zespół Behçeta
Stan zapalny bez infekcji – niektórzy pacjenci rozwijają przewlekłe zapalenie najądrza, które jest stanem zapalnym nawet bez obecności infekcji. Przewlekłe zapalenie najądrza jest trudne w leczeniu, a antybiotyki nie powinny być stosowane, ponieważ nie ma infekcji.¹²

Jatrogenne i związane z zabiegami przyczyny zapalenia najądrza

Zapalenie najądrza może być również spowodowane przez czynniki jatrogenne i interwencje medyczne:¹

Instrumentacja i cewniki moczowe – są częstymi czynnikami ryzyka ostrego zapalenia najądrza
Zapalenie najądrza może rozwinąć się po operacji lub badaniu diagnostycznym, które obejmuje pęcherz moczowy lub cewkę moczową. Może również wystąpić po wprowadzeniu cewnika w celu zebrania moczu.¹
Czynniki ryzyka zapalenia najądrza obejmują: niedawną operację, wcześniejsze problemy strukturalne w drogach moczowych, regularne stosowanie cewnika w cewce moczowej.¹

Leczenie i konsekwencje

Postępowanie terapeutyczne

Leczenie zapalenia najądrza obejmuje leczenie podstawowej infekcji i łagodzenie objawów:¹

Antybiotyki – typowe leczenie obejmuje antybiotyki, takie jak doksycyklina i ceftriakson, podawane przez 4 do 6 tygodni w przypadku pacjentów z przewlekłym zapaleniem najądrza. Lekarz prawdopodobnie będzie leczył pacjenta antybiotykami podawanymi dożylnie, w zastrzyku lub doustnie (przez 10 dni lub dłużej). Często leczenie zależy od identyfikacji zakażających bakterii; wielu lekarzy decyduje się na leczenie co najmniej dwoma różnymi antybiotykami, ponieważ pacjenci czasami są zakażeni więcej niż jednym organizmem.¹
Operacja – jest inną opcją, jeśli żadne inne leczenie nie przyniosło efektów. Polega na usunięciu całości lub części najądrza. Interwencje chirurgiczne mogą być również konieczne w celu skorygowania wszelkich anomalii fizycznych, które mogą powodować zapalenie najądrza. W niektórych przypadkach konieczne może być drenowanie ropni.¹²

Długoterminowe konsekwencje i zapobieganie

Długoterminowe problemy wynikające z zapalenia najądrza u pacjentów są bardzo prawdopodobnie związane z nieodwracalnym rozwojem niedrożności przewodów i przebudową tkanki włóknistej, która występuje pomimo leczenia antybiotykami i eliminacji bakterii.¹²

Niepłodność i niedobór hormonów mogą być trwałym uszkodzeniem spowodowanym przedłużającym się zapaleniem najądrza i zapaleniem jąder.¹
Szczególnie niebezpiecznym powikłaniem zapalenia najądrza i zapalenia jąder jest miejscowe gromadzenie się ropy, znane jako tworzenie się ropnia.¹
Istotność terapii wspomagających, które zapobiegają transformacji architektury tkanki i zachowują płodność.¹

Jeśli zapalenie najądrza jest odpowiednio leczone antybiotykami, powinno zostać wyleczone, a pacjent będzie miał doskonałe rokowanie.¹ Jednak należy zawsze jak najszybciej skonsultować się z lekarzem w przypadku zapalenia jąder i najądrza, aby uniknąć nieodwracalnych uszkodzeń.¹

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Materiały źródłowe

#1 Epididymitis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK430814/
Epididymitis most often occurs as a result of a bacterial infection. In the case of a sexually transmitted disease, bacteria are introduced during sexual intercourse and migrate through the genitourinary tract to the epididymis. […] In cases of infection due to urinary tract infection, retrograde flow of urine or stagnation of urine along the genitourinary tract results in infection of the epididymis. […] When epididymitis is caused by repetitive movements, the mobility of the scrotum and its contents can result in inflammation of the testes or the epididymis. Certain viruses, namely mumps virus, have a predisposition to infect the testis.
#1 Epididymitis – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/epididymitis/symptoms-causes/syc-20363853
Epididymitis is most often caused by a bacterial infection, including sexually transmitted infections (STIs), such as gonorrhea or chlamydia. […] Causes of epididymitis include: […] STIs. Gonorrhea and chlamydia are the most common causes of epididymitis in young, sexually active males. […] Other infections. Bacteria from a urinary tract or prostate infection might spread from the infected site to the epididymis. Also, viral infections, such as the mumps virus, can result in epididymitis. […] Urine in the epididymis. This condition occurs when urine flows backward into the epididymis, causing chemical irritation. It may be the result of heavy lifting or straining. […] Trauma. A groin injury can cause epididymitis. […] Tuberculosis. Rarely, epididymitis can be caused by tuberculosis infection.
#1 Epididymitis and Orchitis: An Overview | AAFP
https://www.aafp.org/pubs/afp/issues/2009/0401/p583.html/1000
Epididymitis is the most common cause of intrascrotal inflammation, and retrograde ascent of pathogens is the usual route of infection. […] Although epididymitis was historically thought to be caused by chemical irritation from urine reflux, a study published in 1979 showed that bacteria were responsible for most cases. […] In men 14 to 35 years of age, epididymitis is most commonly caused by sexually transmitted Neisseria gonorrhoeae or Chlamydia trachomatis infection. […] Nonspecific bacterial epididymitis is caused by various aerobic bacteria and is often associated with anatomic abnormalities. […] In those younger than 14 years or older than 35 years, epididymitis is generally caused by infection with common urinary tract pathogens, such as Escherichia coli. […] In men who practice insertive anal intercourse, coliform bacteria (e.g., E. coli) are common causative pathogens, although Haemophilus influenzae infection has also been linked.
#1 Epididymitis – Clinical Features – Management – TeachMeSurgery
https://teachmesurgery.com/urology/genital-tract/epididymitis/
Epididymo-orchitis is usually caused by local extension of infection from the lower urinary tract (bladder and urethra), either via enteric (i.e. classic UTI) or non-enteric (i.e. sexually transmitted) organisms. […] In males aged 35 years old, the most likely mechanism is sexual transmission, therefore the most common organisms* are N. gonorrhoeae and C. trachomatis. […] In males aged 35 years old, an enteric organism from a urinary tract infection is the more likely mechanism of the disease**. Therefore, the most common pathogens are E. coli, Proteus spp., Klebsiella pneumoniae, and Pseudomonas aeruginosa. […] This is often secondary to a bladder outflow obstruction from prostatic enlargement, leading to retrograde ascent of the pathogen.
#1 Epididymitis: Practice Essentials, Anatomy, Etiology
https://emedicine.medscape.com/article/436154-overview
The exact etiology of acute epididymitis is unclear; however, it is believed to be caused by the retrograde passage of urine from the prostatic urethra to the epididymis via the ejaculatory ducts and vas deferens. Obstruction of the prostate or urethra and congenital anomalies create a predisposition for reflux. Normally, the oblique angle of the ejaculatory ducts through the dense prostatic tissue prevents reflux. Fifty-six percent of men older than 60 years who have epididymitis exhibit concurrent bladder outlet obstruction (BOO), such as a urethral stricture or benign prostatic hyperplasia (BPH). […] Reflux may also be induced by Valsalva maneuvers or strenuous exertion. This can be seen in athletes such as weight lifters. Epididymitis is commonly found to develop during strenuous exertion in conjunction with a full bladder.
#1 Epididymitis: An Overview | AAFP
https://www.aafp.org/pubs/afp/issues/2016/1101/p723.html
Inflammation of the epididymis, or epididymitis, is commonly seen in the outpatient setting. […] Although the etiology is largely unknown, reflux of urine into the ejaculatory ducts is considered the most common cause of epididymitis in children younger than 14 years. […] In boys younger than 14 years, the cause is largely unknown but may be related to anatomic abnormalities causing reflux of infected or sterile urine into the ejaculatory ducts. […] In those older than 35 years, acute epididymitis is most commonly caused by the retrograde flow of infected urine (bacteriuria) into the ejaculatory duct in the setting of bladder outlet obstruction, usually secondary to prostatic hypertrophy. […] Noninfectious acute epididymitis may be an adverse reaction to a medication or caused by reflux of sterile urine into the vas deferens because of bladder outlet obstruction or an underlying systemic disease (e.g., sarcoidosis, Behet syndrome).
#1 Epididymitis and Epididymo-orchitis – Men’s Health Issues – Merck Manual Consumer Version
https://www.merckmanuals.com/home/men-s-health-issues/penile-and-testicular-disorders/epididymitis-and-epididymo-orchitis
Epididymitis i epididymo-orchitis sÄ zazwyczaj spowodowane infekcjÄ bakteryjnÄ. […] Czasami nie ma Å¼adnej infekcji. W takich przypadkach lekarze uwaÅ¼ajÄ, Å¼e najÄ siÄ zapalenie najÄdrza przez odwrotny przepÅyw moczu do najÄdrza, byÄ moÅ¼e z powodu wysiÅku (gdy mÄÅ¼czyÅºni podnoszÄ coÅ bardzo ciÄÅ¼kiego).
#1 Epididymitis and Orchitis | Concise Medical Knowledge
https://www.lecturio.com/concepts/epididymitis-and-orchitis/
Amiodarone Amiodarone An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting potassium channels and voltage-gated sodium channels. There is a resulting decrease in heart rate and in vascular resistance. Pulmonary Fibrosis: Secondary to high drug concentrations at the head of the epididymis Epididymis The convoluted cordlike structure attached to the posterior of the testis. Epididymis consists of the head (caput), the body (corpus), and the tail (cauda). A network of ducts leaving the testis joins into a common epididymal tubule proper which provides the transport, storage, and maturation of spermatozoa. Testicles: Anatomy.
#1 Epididymitis | Altru Health System
https://www.altru.org/health-library/conditions/epididymitis
Epididymitis is most often caused by a bacterial infection, including sexually transmitted infections (STIs), such as gonorrhea or chlamydia. […] Causes of epididymitis include: STIs. Gonorrhea and chlamydia are the most common causes of epididymitis in young, sexually active males. […] Other infections. Bacteria from a urinary tract or prostate infection might spread from the infected site to the epididymis. Also, viral infections, such as the mumps virus, can result in epididymitis. […] Urine in the epididymis. This condition occurs when urine flows backward into the epididymis, causing chemical irritation. It may be the result of heavy lifting or straining. […] Trauma. A groin injury can cause epididymitis. […] Tuberculosis. Rarely, epididymitis can be caused by tuberculosis infection.
#1 Epididymitis: revelations at the convergence of clinical and basic sciences
https://pmc.ncbi.nlm.nih.gov/articles/PMC4577585/
Acute epididymitis represents a common medical condition in the urological outpatient clinic. Mostly, epididymitis is caused by bacterial ascent through the urogenital tract, with pathogens originating either from sexually transmitted diseases or urinary tract infections. […] Accumulated data provide evidence of a differential expression of immune cells, immunoregulatory genes and pathogen-sensing molecules along the length of the epididymal duct. The evidence suggests that a tolerogenic environment exists in the caput epididymidis, but that inflammatory responses are most intense toward the cauda epididymidis. […] However, severe inflammatory responses, particularly in the cauda, may lead to collateral damage to the structure and function of the epididymis. […] In summary, there is evidence that the differential expression of immunoregulatory genes, including IDO and activin A, and pathogen detection mechanisms, such as the TLRs, along the length of the epididymal duct leads to an environment where tolerogenic responses are more favored in the regions proximal to the testis, while antigen-specific immunity and inflammation responses are most vigorous in the cauda. […] Long-term problems resulting from epididymitis in patients are very likely linked to the irreversible development of ductal obstruction and fibrotic tissue remodeling that occurs despite antibiotic treatment and eradication of bacteria.
#1
https://journals.lww.com/10.4103/1008-682X.155770
In summary, there is evidence that the differential expression of immunoregulatory genes, including IDO and activin A, and pathogen detection mechanisms, such as the TLRs, along the length of the epididymal duct leads to an environment where tolerogenic responses are more favored in the regions proximal to the testis, while antigen-specific immunity and inflammation responses are most vigorous in the cauda. This would be consistent with the need to protect sperm emerging from the testis, without compromising the ability to respond to ascending infections. […] Long-term problems resulting from epididymitis in patients are very likely linked to the irreversible development of ductal obstruction and fibrotic tissue remodeling that occurs despite antibiotic treatment and eradication of bacteria. This highlights the importance of adjuvant therapies, which prevent the transformation of the tissue architecture and preserve fertility.
#1 Epididymitis and Orchitis: An Overview | AAFP
https://www.aafp.org/pubs/afp/issues/2009/0401/p583.html/1000
Other pathogens that are less commonly associated with epididymitis include Ureaplasma urealyticum, Proteus mirabilis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. […] Epididymitis secondary to Mycobacterium tuberculosis infection is rare but must be considered among those at high risk. […] Noninfectious etiologies of epididymitis have been identified in numerous groups. […] One study found that the annual incidence of epididymitis in boys two to 13 years of age is 1.2 per 1,000, and that the condition in this age group is primarily a postinfectious inflammatory reaction to pathogens (e.g., Mycoplasma pneumoniae, enteroviruses, adenoviruses) that follows a benign course. […] Other noninfectious causes of epididymitis include vasculitides and certain medications, such as amiodarone (Cardarone).
#1 Epididymitis/orchitis | 5-Minute Emergency Consult
https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307739/all/Epididymitis_orchitis
Epididymitis: Pathogenesis: Initial stages: Cellular inflammation begins in vas deferens, descends to epididymis […] Acute phase: Epididymis is swollen and indurated in upper and lower poles […] Testis may become edematous owing to passive congestion or inflammation […] Resolution: May be complete without sequelae […] Peritubular fibrosis may develop, occluding ductules.
#1 Epididymitis Explained: Causes, Symptoms, and How It’s Treated
https://progenesisivf.com/blog/epididymitis-explained/
Bacterial infection is the leading cause of acute epididymitis. […] The most prevalent cause of epididymitis in people under the age of 35 is sexually transmitted infections (STIs), such as gonorrhea or chlamydia. […] If you are over 35, the most common cause of epididymitis is the backflow of infected urine down the ejaculatory tube to the epididymis. The most prevalent bacteria associated with this is E. coli. […] Epididymitis can also be caused by infections such as the mumps virus or, in rare cases, tuberculosis. […] Chronic epididymitis: Inflammation can remain even if there is no bacterial infection. […] Testicular tissue death: This can occur when the testicle does not receive enough blood flow. […] Infertility: In rare circumstances, epididymitis can induce infertility. […] Epididymo-orchitis: It occurs when an infection travels from the epididymis to the testicle.
#1 Case report on secondary testicular necrosis due to fulminant epididymitis: ultrasonographic evaluation and diagnosis | BMC Urology | Full Text
https://bmcurol.biomedcentral.com/articles/10.1186/s12894-020-00655-w
Testicular necrosis is a rare presentation of epididymitis in the emergency department, with an estimated incidence of 12% of all epididymitis cases. […] Our case highlights the benefit of ultrasonography of the testis. This case initially showed clear hyperperfusion with a rapid change to hypoperfusion. The latter being strongly associated with testicular necrosis. […] Testicular necrosis is caused by venous occlusion from the testes. The mechanism of this para-infectious thrombosis is not entirely clear. Suggested mechanisms contributing to this testicular necrosis could be venous compression by oedema of the epididymis, swelling of the funiculus in case of funiculitis or edema at the external inguinal ring. Besides this, bacterial toxins may damage endothelial cells with induction of vascular thrombosis.
#1 Case report on secondary testicular necrosis due to fulminant epididymitis: ultrasonographic evaluation and diagnosis | BMC Urology | Full Text
https://bmcurol.biomedcentral.com/articles/10.1186/s12894-020-00655-w
In rodents infected with E Coli, necrosis is found to be the primary cell death mechanism. This effect is primarily seen in Sertoli cells in infected testis with impaired spermatogenesis due to the lack of supporting germ cells. This lowering of spermatogenesis after infectious necrosis is also seen in human testis. […] To our knowledge, this is the first case that proved funiculitis to co-exist in loss of colour doppler on pathological evaluation.
#1
https://www.scielo.br/j/ibju/a/MMTRhnDcL9frD9MrFCS7NQD/?lang=en
Epididymitis in patients with anorectal malformation (ARM) represents a unique problem because unlike the general population, an underlying urinary tract problem is frequently identified. […] The pathophysiology of voiding dysfunction can lead to external urethral sphincter dyssynergia during voiding resulting in elevated urethral pressure and subsequent retrograde urethral-vasal reflux with inflammation and pain. […] The combination of epididymitis and ARM can be an indicator of significant renal and bladder dysfunction. […] Therefore we strongly advocate for a comprehensive urologic evaluation to elucidate the etiology behind the epididymitis in the ARM patient population. […] A significant proportion of patients in our series also had evidence of renal injury or neurogenic bladder.
#1 Epididymo-orchitis risk factors in traumatic spinal cord injured patients | Spinal Cord
https://www.nature.com/articles/3101491
The pathophysiology of epididymitis remains unclear. […] In a study of 22 men with Escherichia coli or idiopathic acute epididymitis, and nine controls, urethrovasal reflux secondary to high voiding pressures was suggested as the mechanism of E-O. […] The main finding from our study was that patients with muscular spasm are at a decreased risk of E-O. Muscular spasm includes detrusor, external urethral sphincter, and lower limbs muscular spasm. […] The mechanism for spasm protecting against E-O could be explained by patients with flaccid bladders having asymptomatic, prolonged UTI.
#1 Epididymitis: Practice Essentials, Anatomy, Etiology
https://emedicine.medscape.com/article/436154-overview
Instrumentation and indwelling catheters are common risk factors for acute epididymitis. […] Epididymitis may be accompanied by urethritis or prostatitis. […] The etiology of chronic epididymitis includes the following: Inadequate treatment of acute epididymitis, Recurrent epididymitis, Association with a granulomatous reaction (most commonly Mycobacterium tuberculosis), Association with a chronic disease process such as Behet syndrome.
#1 Epididymitis | Better Health Channel
https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/epididymitis
Epididymitis is inflammation of the epididymis, usually caused by an infection. […] Most cases of epididymitis are caused by bacterial infection from a urinary tract infection (UTI) or a sexually transmissible infection (STI) such as gonorrhoea or chlamydia. […] Epididymitis is usually a secondary bacterial infection that can be triggered by a range of conditions such as an urinary tract infection (UTI) or a sexually transmissible infection (STI). […] The bacteria in the urethra (the tube carrying urine and sperm from the penis) move through the urinary and reproductive structures to the epididymis. […] Some people develop chronic epididymitis which is inflammation even when there is no infection. […] Chronic epididymitis is difficult to treat. Antibiotics should not be used, as there is no infection.
#1 Epididymitis and orchitis Guide: Causes, Symptoms and Treatment Options
https://www.drugs.com/health-guide/epididymitis-and-orchitis.html
Some men have a history of UTIs or prostate infections. For them, epididymitis usually is caused by intestinal bacteria that have spread from the infected site. […] Epididymitis may develop after surgery or a diagnostic test that involves the bladder or urethra. Or it may occur after a catheter has been inserted to collect urine. […] Rarely, epididymitis can occur when a systemic (whole body) infection spreads through the bloodstream and moves to the epididymis. […] A noninfectious form of this condition can occur. Often the exact cause remains unknown. It sometimes develops in men who take amiodarone (Cordarone, Pacerone). This is a heart medication that seems to build up in the epididymis. […] Some cases have been blamed on intense exercise, especially heavy lifting. The strain of heavy lifting may force urine from the bladder into the epididymis. There, it can cause a form of chemical irritation that triggers epididymitis.
#1 Epididymitis Information | Mount Sinai – New York
https://www.mountsinai.org/health-library/diseases-conditions/epididymitis
Epididymitis is swelling (inflammation) of the tube that connects the testicle with the vas deferens. The tube is called the epididymis. […] Epididymitis is most often caused by a bacterial infection. Infection often begins in the urethra, the prostate, or the bladder. Gonorrhea and chlamydia infections are most often the cause of the problem in young heterosexual men. In children and older men, it is more commonly caused by E coli and similar bacteria. This is also true in men who have sex with men. […] Mycobacterium tuberculosis (TB) can cause epididymitis. Other bacteria (such as Ureaplasma) may also cause the condition. […] Amiodarone is a medicine which prevents abnormal heart rhythms. This medicine can also cause epididymitis. […] The following increase the risk for epididymitis: Recent surgery, Past structural problems in the urinary tract, Regular use of a urethral catheter, Sexual intercourse with more than one partner and not using condoms, Enlarged prostate.
#1 Epididymitis: Symptoms, Causes, Treatment, and More
https://www.healthline.com/health/epididymitis
However, a nonsexually transmitted infection, such as a UTI or prostate infection, can also cause epididymitis. […] Chronic epididymitis, on the other hand, lasts 6 weeks or more. […] Treatment for epididymitis involves treating the underlying infection and easing symptoms. […] Common treatments include antibiotics like doxycycline and ceftriaxone, which a healthcare professional administers for 4 to 6 weeks for people with chronic epididymitis. […] Surgery is another option if no other treatments have been successful. This involves removing all or part of the epididymis. Surgical interventions may also be necessary to correct any physical anomalies that may be causing epididymitis.
#1 Epididymitis (Testicle Infection) Diagnosis, Causes, Treatment
https://www.emedicinehealth.com/testicle_infection_epididymitis/article_em.htm
The health care practitioner likely will treat the individual with antibiotics through an IV, a shot, or pills orally (to be taken for 10 days or longer). Often the treatment depends on the identity of the infecting bacteria; many physicians elect to treat with at least two different antibiotics because individuals are occasionally infected with more than one organism. […] If treated appropriately with antibiotics, epididymitis should be cured and the individual will have an excellent prognosis (outlook).
#1 Epididymitis: Causes, Symptoms, and Treatments
https://www.webmd.com/men/what-is-epididymitis
You may need surgery to drain any pus-filled tissue (abscesses). In some cases, your doctor may need to take out all or part of your epididymis (epididymectomy). If you have urinary tract abnormalities, surgery may be able to fix the problem thats causing epididymitis. […] Bacterial infections are behind most cases of epididymitis. This commonly includes sexually transmitted infections such as gonorrhea and chlamydia, but also germs that cause urinary tract, bladder, or prostate infections. Some viruses can also trigger inflammation in your epididymis.
#1 Epididymitis and inflammation of the testicles – USZ
https://www.usz.ch/en/disease/epididymitis-and-inflammation-of-the-testicles/
However, if the therapy is not fully effective or has not been treated for long enough, epididymitis can become chronic. […] This increases the risk of infertility. […] Inadequately treated testicular inflammation also carries the risk that testosterone is no longer produced in line with age. […] Infertility and hormone deficiency can therefore be the permanent damage caused by protracted epididymitis and testicular inflammation. […] A particularly dangerous complication of epididymitis and testicular inflammation is the local accumulation of pus, known as abscess formation. […] You should therefore always have inflammation of the testicles and epididymis checked by a doctor as soon as possible in order to avoid irreversible consequential damage.
#2
https://www.advocatehealth.com/health-services/urology/epididymitis
Epididymitis is the inflammation of the epididymis, a small, coiled tube responsible for storing and transporting sperm. This inflammatory condition may cause orchitis, which is the inflammation of one or both testicles. […] Several factors may contribute to the development of epididymitis, such as bacterial infections, sexually transmitted infections (STIs) or urinary tract infections (UTIs). […] Epididymitis can stem from several causes. However, the spread of bacterial infection is the most common cause of epididymitis. Sexually transmitted infections such as chlamydia and gonorrhea are often the cause of epididymitis in younger men.
#2 Epididymitis: revelations at the convergence of clinical and basic sciences
https://pmc.ncbi.nlm.nih.gov/articles/PMC4577585/
Acute epididymitis represents a common medical condition in the urological outpatient clinic. Mostly, epididymitis is caused by bacterial ascent through the urogenital tract, with pathogens originating either from sexually transmitted diseases or urinary tract infections. […] Accumulated data provide evidence of a differential expression of immune cells, immunoregulatory genes and pathogen-sensing molecules along the length of the epididymal duct. The evidence suggests that a tolerogenic environment exists in the caput epididymidis, but that inflammatory responses are most intense toward the cauda epididymidis. […] However, severe inflammatory responses, particularly in the cauda, may lead to collateral damage to the structure and function of the epididymis. […] In summary, there is evidence that the differential expression of immunoregulatory genes, including IDO and activin A, and pathogen detection mechanisms, such as the TLRs, along the length of the epididymal duct leads to an environment where tolerogenic responses are more favored in the regions proximal to the testis, while antigen-specific immunity and inflammation responses are most vigorous in the cauda. […] Long-term problems resulting from epididymitis in patients are very likely linked to the irreversible development of ductal obstruction and fibrotic tissue remodeling that occurs despite antibiotic treatment and eradication of bacteria.
#2 Epididymitis and orchitis Guide: Causes, Symptoms and Treatment Options
https://www.drugs.com/health-guide/epididymitis-and-orchitis.html
Epididymitis is an inflammation of the epididymis. The epididymis is the coiled tube at the back of the testicle. In most cases, an infection causes this inflammation. […] Infections that cause epididymitis usually are related to age, medical history and sexual activity. […] The most common cause of epididymitis is a sexually transmitted disease (STD). The STD is usually chlamydia, gonorrhea or both. […] The initial site of infection is the urethra. This is the tube-like passageway that carries urine and semen out of the penis. Eventually, bacteria spread backward through the reproductive tract to attack the epididymis. […] Among men who have anal intercourse, epididymitis can be caused by intestinal bacteria from the anus. These bacteria enter the urethra through the penis. They then travel backward through the reproductive tract.
#2 Epididymitis: Practice Essentials, Anatomy, Etiology
https://emedicine.medscape.com/article/436154-overview
The exact etiology of acute epididymitis is unclear; however, it is believed to be caused by the retrograde passage of urine from the prostatic urethra to the epididymis via the ejaculatory ducts and vas deferens. Obstruction of the prostate or urethra and congenital anomalies create a predisposition for reflux. Normally, the oblique angle of the ejaculatory ducts through the dense prostatic tissue prevents reflux. Fifty-six percent of men older than 60 years who have epididymitis exhibit concurrent bladder outlet obstruction (BOO), such as a urethral stricture or benign prostatic hyperplasia (BPH). […] Reflux may also be induced by Valsalva maneuvers or strenuous exertion. This can be seen in athletes such as weight lifters. Epididymitis is commonly found to develop during strenuous exertion in conjunction with a full bladder.
#2 A Really Big Pain: Acute Epididymitis
https://www.patientcareonline.com/view/really-big-pain-acute-epididymitis
A 24-year-old man with a history of HIV infection (CD4+ cell count, 746/L [32%]; HIV RNA level, 980 copies/mL; nadir CD4+ cell count, 482/L [29%]), secondary syphilis, major depression, and intermittent crystal methamphetamine use presented to the emergency department with a 1-week history of gradually increasing pain and swelling in the left side of his scrotum, 2 days of fever (temperature to 38.6C [101.5F]), and chills. […] The cause of acute epididymitis can be infectious or noninfectious; most cases are infectious in origin. Although the pathophysiology is still unproven, the most commonly accepted hypothesis is retrograde flow of infected urine into the ejaculatory duct. […] For men 35 years or younger, the most frequent cause of infectious epididymitis is C trachomatis or N gonorrhoeae. Coliforms are the most common causes of epididymitis in men older than 35 years, with Escherichiacoli being the most frequently found organism.
#2 Epididymitis: Causes, Symptoms, and Treatments
https://www.webmd.com/men/what-is-epididymitis
Epididymitis is inflammation of the epididymis a long, coiled tube at the back of the testes. Its usually caused by bacteria, like the kind that cause sexually transmitted infections, but you can get epididymitis for other reasons. […] People usually get epididymitis because of a bacterial infection. This commonly includes germs that cause sexually transmitted infections, such as gonorrhea and chlamydia. But the most likely cause of epididymitis largely depends on your age. […] Other causes of epididymitis include: Urinary tract or bladder infections. Bacteria can spread from your urinary system to your testicles. This is the most common cause of epididymitis in people who have a penis who are older than 35. […] Reverse urine flow. Chemicals in your pee can be irritating if they reach your epididymis. This may happen if something blocks urine from leaving your urethra or your pee flows backward for another reason like you lift something heavy and put strain on your urinary system.
#2 Epididymitis | Better Health Channel
https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/epididymitis
Epididymitis is inflammation of the epididymis, usually caused by an infection. […] Most cases of epididymitis are caused by bacterial infection from a urinary tract infection (UTI) or a sexually transmissible infection (STI) such as gonorrhoea or chlamydia. […] Epididymitis is usually a secondary bacterial infection that can be triggered by a range of conditions such as an urinary tract infection (UTI) or a sexually transmissible infection (STI). […] The bacteria in the urethra (the tube carrying urine and sperm from the penis) move through the urinary and reproductive structures to the epididymis. […] Some people develop chronic epididymitis which is inflammation even when there is no infection. […] Chronic epididymitis is difficult to treat. Antibiotics should not be used, as there is no infection.
#2 Epididymitis Information | Mount Sinai – New York
https://www.mountsinai.org/health-library/diseases-conditions/epididymitis
Epididymitis is swelling (inflammation) of the tube that connects the testicle with the vas deferens. The tube is called the epididymis. […] Epididymitis is most often caused by a bacterial infection. Infection often begins in the urethra, the prostate, or the bladder. Gonorrhea and chlamydia infections are most often the cause of the problem in young heterosexual men. In children and older men, it is more commonly caused by E coli and similar bacteria. This is also true in men who have sex with men. […] Mycobacterium tuberculosis (TB) can cause epididymitis. Other bacteria (such as Ureaplasma) may also cause the condition. […] Amiodarone is a medicine which prevents abnormal heart rhythms. This medicine can also cause epididymitis. […] The following increase the risk for epididymitis: Recent surgery, Past structural problems in the urinary tract, Regular use of a urethral catheter, Sexual intercourse with more than one partner and not using condoms, Enlarged prostate.
#2 A Really Big Pain: Acute Epididymitis
https://www.patientcareonline.com/view/really-big-pain-acute-epididymitis
However, these enteric organisms are also a common cause of sexually transmitted epididymitis among men who engage in insertive anal intercourse. Other, rarer causative organisms include Brucella species, Salmonella species, Mycobacterium tuberculosis, Candida species, and Cytomegalovirus. The latter 3 organisms are more common in immunosuppressed HIV-positive patients. […] Even rarer are the noninfectious causes of epididymitis. These include sarcoidosis, vasculitic diseases (eg, Behet disease), and use of amiodarone.
#2 Epididymitis and Orchitis: An Overview | AAFP
https://www.aafp.org/pubs/afp/issues/2009/0401/p583.html/1000
Other pathogens that are less commonly associated with epididymitis include Ureaplasma urealyticum, Proteus mirabilis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. […] Epididymitis secondary to Mycobacterium tuberculosis infection is rare but must be considered among those at high risk. […] Noninfectious etiologies of epididymitis have been identified in numerous groups. […] One study found that the annual incidence of epididymitis in boys two to 13 years of age is 1.2 per 1,000, and that the condition in this age group is primarily a postinfectious inflammatory reaction to pathogens (e.g., Mycoplasma pneumoniae, enteroviruses, adenoviruses) that follows a benign course. […] Other noninfectious causes of epididymitis include vasculitides and certain medications, such as amiodarone (Cardarone).
#2 Epididymitis – Genitourinary Disorders – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/genitourinary-disorders/penile-and-scrotal-disorders/epididymitis
Most epididymitis (and epididymo-orchitis) is caused by bacteria. […] In men 35 years, most cases are due to a sexually transmitted pathogen, especially Neisseria gonorrhoeae or Chlamydia trachomatis. Infection may begin as urethritis. […] In men 35 years, most cases are due to gram-negative coliform bacilli and typically occur in patients with urologic abnormalities, indwelling catheters, or recent urologic procedures. […] Epididymitis and epididymo-orchitis of noninfectious etiology may be due to chemical irritation secondary to a retrograde flow of urine into the epididymis, which may occur with Valsalva maneuver (eg, with heavy lifting) or after local trauma. […] Urethritis suggests that the cause of epididymitis is a sexually transmitted pathogen, and a urethral swab is sent for gonococcus and chlamydia nucleic acid amplification testing (NAAT) or culture. […] Treatment of nonbacterial epididymitis includes the above general measures, but antimicrobial therapy is not warranted.
#2
https://journals.lww.com/10.4103/1008-682X.155770
Acute epididymitis represents a common medical condition in the urological outpatient clinic. Mostly, epididymitis is caused by bacterial ascent through the urogenital tract, with pathogens originating either from sexually transmitted diseases or urinary tract infections. […] Animal models of epididymitis are created to delineate the underlying reasons for this observation and the additional impairment of sperm function that is often associated with the disease. Accumulated data provide evidence of a differential expression of immune cells, immunoregulatory genes and pathogen-sensing molecules along the length of the epididymal duct. […] The evidence suggests that a tolerogenic environment exists in the caput epididymidis, but that inflammatory responses are most intense toward the cauda epididymidis. This is consistent with the need to provide protection for the neo-antigens of spermatozoa emerging from the testis, without compromising the ability to respond to ascending infections. However, severe inflammatory responses, particularly in the cauda, may lead to collateral damage to the structure and function of the epididymis.
#2 Epididymitis and inflammation of the testicles – USZ
https://www.usz.ch/en/disease/epididymitis-and-inflammation-of-the-testicles/
Inflammation of the epididymis (epididymitis) is common and is sometimes accompanied by simultaneous inflammation of the testicles (orchitis). […] In epididymitis, pathogens such as viruses, bacteria and, in rare cases, fungi infect the epididymis. […] The main causes of epididymitis and testicular inflammation are intestinal bacteria such as Escherichia coli, Klebsiella and enterococci. Staphylococci also play a role, rarely also fungi/yeasts. […] Testicular torsion, i.e. twisting of the testicle, can also lead to epididymitis/orchitis. […] However, bacteria and viruses are by far the most common cause. These ascend via the urethra and the seminal ducts into the epididymis, in such cases this is medically referred to as an ascending infection. […] A severe case of mumps can cause a reduction in fertility or even lead to infertility.
#2 Epididymitis and inflammation of the testicles – USZ
https://www.usz.ch/en/disease/epididymitis-and-inflammation-of-the-testicles/
However, if the therapy is not fully effective or has not been treated for long enough, epididymitis can become chronic. […] This increases the risk of infertility. […] Inadequately treated testicular inflammation also carries the risk that testosterone is no longer produced in line with age. […] Infertility and hormone deficiency can therefore be the permanent damage caused by protracted epididymitis and testicular inflammation. […] A particularly dangerous complication of epididymitis and testicular inflammation is the local accumulation of pus, known as abscess formation. […] You should therefore always have inflammation of the testicles and epididymis checked by a doctor as soon as possible in order to avoid irreversible consequential damage.
#2
https://journals.lww.com/10.4103/1008-682X.155770
In summary, there is evidence that the differential expression of immunoregulatory genes, including IDO and activin A, and pathogen detection mechanisms, such as the TLRs, along the length of the epididymal duct leads to an environment where tolerogenic responses are more favored in the regions proximal to the testis, while antigen-specific immunity and inflammation responses are most vigorous in the cauda. This would be consistent with the need to protect sperm emerging from the testis, without compromising the ability to respond to ascending infections. […] Long-term problems resulting from epididymitis in patients are very likely linked to the irreversible development of ductal obstruction and fibrotic tissue remodeling that occurs despite antibiotic treatment and eradication of bacteria. This highlights the importance of adjuvant therapies, which prevent the transformation of the tissue architecture and preserve fertility.
#2 Case report on secondary testicular necrosis due to fulminant epididymitis: ultrasonographic evaluation and diagnosis | BMC Urology | Full Text
https://bmcurol.biomedcentral.com/articles/10.1186/s12894-020-00655-w
Testicular necrosis is a rare presentation of epididymitis in the emergency department, with an estimated incidence of 12% of all epididymitis cases. […] Our case highlights the benefit of ultrasonography of the testis. This case initially showed clear hyperperfusion with a rapid change to hypoperfusion. The latter being strongly associated with testicular necrosis. […] Testicular necrosis is caused by venous occlusion from the testes. The mechanism of this para-infectious thrombosis is not entirely clear. Suggested mechanisms contributing to this testicular necrosis could be venous compression by oedema of the epididymis, swelling of the funiculus in case of funiculitis or edema at the external inguinal ring. Besides this, bacterial toxins may damage endothelial cells with induction of vascular thrombosis.
#2 Epididymitis: Symptoms, Causes, Treatment, and More
https://www.healthline.com/health/epididymitis
However, a nonsexually transmitted infection, such as a UTI or prostate infection, can also cause epididymitis. […] Chronic epididymitis, on the other hand, lasts 6 weeks or more. […] Treatment for epididymitis involves treating the underlying infection and easing symptoms. […] Common treatments include antibiotics like doxycycline and ceftriaxone, which a healthcare professional administers for 4 to 6 weeks for people with chronic epididymitis. […] Surgery is another option if no other treatments have been successful. This involves removing all or part of the epididymis. Surgical interventions may also be necessary to correct any physical anomalies that may be causing epididymitis.