A rare case of a testicular lesion related to hand, foot, and mouth disease

Hand, foot, and mouth disease generally occurs in children. In rare cases, hand, foot, and mouth disease affects the testicles.


Introduction
HFMD is an infectious disease in which droplet, contact, or fecal-oral infection with CVA6, CVA10, and CVA16 or enterovirus 71 induces vesicular exanthema measuring 2 to 3 mm in diameter on distal parts of the extremities, such as the dorsal palms and soles and oral mucosa.We herein report a 29-year-old male with a testicular lesion related to HFMD who received symptomatic therapy and conducted a literature review.

Case presentation
A 29-year-old male developed right testicular pain several days after the onset of HFMD.He took an analgesic, which was ineffective.Therefore, he presented to the Emergency Outpatient Unit of our hospital the next day.His medical/family history was not contributory and there was no episode of trauma.A physical examination showed a body temperature was 36.5°C,right-dominant testicular pain, and an ambulatory status.Partial swelling of the right scrotum without induration was noted.
Ultrasonography showed no laterality in testis sizes (right: 47 9 21 9 22 mm, left: 42 9 24 9 24 mm) or blood flow disturbances.Several nodules with an unclear border were detected in the upper and lower poles of the right testis.Internal echo was slightly heterogeneous in the left testis and there were no nodules (Fig. 1).
The patient was orally administered cefuroxime for 7 days to reduce inflammation.Testicular pain recurred 13 days after the initial consultation and the patient consulted our hospital.Partial swelling of the right scrotum with induration was observed, but with a reduction in the hypoechoic area; therefore, an analgesic was prescribed.Thereafter, pain did not recur, and normal findings were observed in a 6-month follow-up.The course of ultrasonography findings is shown in Figure 2.

Discussion
Orchitis related to mumps virus infection accounts for 20% to 30% of cases of testicular pain in adult males.However, testicular pain and scrotal swelling have also been reported in some patients with CVA6, adenovirus, enterovirus, or COVID-19 infection. 1,2Di Lella et al., a lesional PCR swab was positive for coxsackievirus from the patient's papulovesicular rash on his palms, nose and feet. 2 Vuorinen et al. described a CVA6-infected patient who simultaneously developed HFMD and epididymitis and reported that antimicrobial administration attenuated these conditions. 3Epididymitis is characterized by swelling of the epididymis and increased blood flow on color Doppler ultrasonography. 4Tarantino et al., grayscale sonography of the scrotum can show 1 or more indicative features in patients with epididymo-orchitis of mumps virus infection: focal or diffuse enlargement of the epididymis with an anomalous echo texture, an enlarged dedimus with a heterogeneous echo texture, hydrocele, and scrotal skin thickening.The presence of hyperemia on color Doppler ultrasonography was the only sonographic sign of inflammation in 40% of cases of orchitis. 5Singh et al., 30%-50% of patients showed testis atrophy after mumps orchitis.Although testicular cancer is not casually associated with mumps epididymo-orchitis, it has been reported in men with testicular atrophy secondary to mumps. 6n the present case, the ultrasonography showed no laterality in testis sizes or blood flow disturbances in color Doppler, internal echo was slightly heterogeneous in the left testis.After 182 days of the first presentation, each testicular atrophy was not seen in ultrasonography.If ultrasonography reveals a tumorous lesion or nodule in the testis, it needs to be differentiated from a testicular tumor in adults.In these cases, early orchidectomy must be considered, assuming lesion metastasis or disease progression. 3In the present case, diseases to be differentiated initially included epididymitis, a testicular tumor, mumps orchitis, testicular torsion, and appendiceal torsion based on the age of the patient at the time of onset, symptoms, and physical findings.There was no finding to indicate urinary tract infection.The patient was negative for tumor markers and the lesion was painful; positive findings for the above diseases were insufficient.Since some infectious diseases induce a mild inflammatory response, we selected antibiotic administration and symptomatic therapy.Although a few case reports of testicular lesions related to HFMD have been published, this condition is extremely rare.Hurtt et al. described two patients with testicular pain after the onset of HFMD, including a 36year-old male who selected and underwent surgical extirpation, namely, orchidectomy, through sufficient counseling on the possibility of early progression or metastasis in the case of a malignant tumor or fertility loss after orchidectomy.In the two patients, pathological findings included inflammatory changes, fibrosis, and hemorrhagic changes.There was no tumor or solid component. 1The follow-up of testicular lesions is not recommended due to the possibility of a malignant tumor or the risk of metastasis.It is very difficult to tell the difference between malignant and benign conditions.If the symptomatic therapy is selected, both testicles should be monitored carefully.If viral infection is considered to be an etiological factor, follow-up by ultrasonography needs to be continued at short intervals to avoid patient anxiety or unnecessary surgical invasion through sufficient patient-shared decision-making. 7In the present case, ultrasonography was performed frequently; therefore, it was possible to serially evaluate the condition.Furthermore, the patient received symptomatic therapy, which ameliorated symptoms in the absence of excessive invasions, such as orchidectomy.

Conclusion
We encountered a patient in whom symptomatic therapy for testicular pain after the onset of HFMD resulted in amelioration.In the present case, diseases to be differentiated included a testicular tumor requiring early orchidectomy; however, the findings obtained were not typical for various diseases, and, thus, symptomatic therapy was selected.The careful selection of treatment options for young adult males with testicular pain/scrotal swelling, such as surgery and symptomatic therapy, based on an interview on their medical history or various examination findings, is important.

Editorial Comment
Editorial Comment to A rare case of a testicular lesion related to hand, foot, and mouth disease This case report demonstrated that coxsackievirus viral orchitis showed an intratesticular mass, resembling testicular cancer. 1 After ruling out testicular cancer, the authors selected a watchful waiting policy for this situation.However, it is very difficult to make a diagnosis correctly without a biopsy or excision.Although viral particles can invade the testis parenchyma through the blood-testis barrier, viral orchitis shows different findings on ultrasound in the testis, as opposed to bacterial epididymo-orchitis.While mumps orchitis showed a homogeneous and or diffused pattern on the ultrasound exam, coxsackievirus orchitis showed a heterogeneous mass in the affected testicles.It is very difficult to tell the difference between malignant and benign conditions.If the wait-and-see policy is selected, both testicles should be monitored carefully.The authors showed the changes in the ultrasound findings over some time.The intratesticular mass finally disappeared after half a year of observation.Additionally, symptomatic therapy such as cooling is essential to prevent testis atrophy.This case report is very important for the readers of the IJU case report.Urologists should know and keep in mind the ultrasound findings of viral orchitis when ruling out testicular neoplasm.Kazuyoshi Johnin MD, PhD Department of Urology, Shiga University of Medical Science, Otsu, Shiga, Japan johnin@belle.shiga-med.ac.jpDOI: 10.1002/iju5.12722

Fig. 1
Fig.1Ultrasonography image of the right testis on the first visit.Testis size was 47 9 21 9 22 mm.Several nodules with an unclear border were detected in the upper and lower poles.

Fig. 2
Fig. 2 The time-elapse ultrasonography images of the right testis.Nodules disappeared 6 months after the first visit.The left-side images of each line are transverse sections, and the right-side images are sagittal sections.(a,b) Day 1; (c,d) Day 5; (e,f) Day 13; (g,h) Day 182.