An unusual location of hand, foot and mouth disease.

Hand, foot, and mouth disease (HFMD) is a childhood febrile disease. Oral lesions and papulovesicular lesions on the hands and feet are the clinical signs of the disease. In our case, a 17-year-old boy presented to the emergency department, where he was diagnosed with HFMD. After 6 days, he felt intense pain in his right testicle, and therefore an ultrasound (US) examination was performed. US detected a hypoechoic mass-like area in the right testis. Viral etiology was suspected, and no therapy was prescribed. After a little more than 3 months, US examination showed a reduced lesion size. Viral epididymo-orchitis should be suspected in young men with a recent history of HFMD and testicular pain.

Background

Hand, foot, and mouth disease (HFMD) is a childhood febrile disease first described by Robinson et al. in Toronto in 1957 [1]. It is caused mainly by coxsackievirus A16, enterovirus 71, coxsackievirus A6, and coxsackievirus A10 [1-3]. HFMD usually occurs in spring and summer [4] and most often in children from 0 to 5 years of age [5, 6] and immunocompromised adults [7], as they may be especially vulnerable to enterovirus 71 and coxsackievirus A16 [8] infections. However, HFMD can also occur in immunocompetent adults [6, 7]. The main routes of transmission are through oropharyngeal secretions or by direct contact with cutaneous lesions, faeces [9], and contaminated objects. The incubation period is short, ranging from 2 to 7 days. Oral lesions are the first clinical signs of the disease, and they are sometimes the only signs, as they appear before the lesions on the extremities [9]. Cutaneous manifestations include multiple papulovesicular lesions on the hands and feet. In most cases, the prognosis is good, with spontaneous healing in 7–10 days without sequelae. Treatment is only symptomatic, also because a virus-specific therapy is not available [10].

Case report

A 17-year-old boy presented to the emergency department with a 4-day history of pharyngitis, general discomfort, and a progressive papulovesicular rash that had started on his palms and subsequently involved his nose and feet. He was diagnosed with HFMD. He underwent chest X-ray, blood tests, and an electrocardiogram; a lesional polymerase chain reaction (PCR) swab was positive for coxsackievirus. No specific therapy was administered. After 6 days, he felt intense pain in his right testicle. He had a mild fever and a swelling on the right side of the scrotum, and there was tenderness on palpation. Testicular torsion was suspected, and an ultrasound (US) examination was therefore performed. US revealed a hypo-isoechoic mass-like area on the right side, with a maximum longitudinal diameter of 19.3 mm, but no signs of vascularization were found at a color Doppler US examination (Fig. 1). With the exception of the hypo-isoechoic area, the testis appeared only slightly increased in size and showed regular vascularization on color Doppler. Nevertheless, orchitis was suspected. No therapy was administered. After 2 weeks, US was repeated, showing that the hypoechoic area was reduced; in particular, the longitudinal diameter was reduced from 19.3 to 17.8 mm (Fig. 2). Viral etiology was suspected. A little more than 3 months later, US examination showed a further reduction in lesion size, from 17 to 7.5 mm. Moreover, the lesion appeared more isoechoic (Fig. 3).

Fig. 1

First US examination: a hypoechoic mass-like area in the right testis, with a maximum longitudinal diameter of 19.3 mm and no signs of vascularization at color Doppler US

Fig. 2

Second US examination: the hypoechoic area is reduced from 19.3 to 17.8 mm

Fig. 3

Third US examination: the lesion size is further reduced from 17.8 to 7.5 mm. The lesion appeared more isoechoic

Discussion

Viral infection is a potential cause of orchitis independently of age [11]. The mumps virus is most commonly involved, but other viruses, such as adenovirus and enterovirus, are also seen [11, 12]. Coxsackievirus, known for causing HFMD, is a type of enterovirus that has been documented as a cause of orchitis. In a case report by Vuorinen et al. [13], a 17-year-old male patient with a diagnosis of HFMD developed epididymo-orchitis caused by coxsackievirus A6 (CV-A6), which is a member of human enterovirus species A in the genus Enterovirus in the family Picornaviridae. In 2008, CV-A6 became known as a cause of HFMD [14]. The characteristics of CV-A6 HFMD are atypical and more severe than those seen in the classic disease, and adults have also been affected [14-17].

La Marca et al. [18] recently reported a case of a young man presenting heavy testicular pain as the first symptom of a COVID-19 infection. Fernandino et al. [19] presented a case similar to ours: a 41-year-old patient with bilateral scrotal masses and a recent previous diagnosis of HFMD. As in our case, the patient underwent only US follow-up, which demonstrated the benignity of the lesion. Tumor markers (alpha fetoprotein, beta-human chorionic gonadotropin) were detected and were within normal limits.

In our case, we first ruled out that it was testicular torsion. We did not find it necessary to detect tumor markers because the lesion on US was not highly suggestive of a malignant lesion [20, 21]; it had no signs of vascularization at color Doppler US as we would expect in a solid mass, and it was reduced in size after 2 weeks.

Moreover, the clinical history did not provide a suspicion of a malignant lesion: the onset of the testicular lesion right after the onset of common HFMD symptoms, and its spontaneous regression, without any therapy, was highly suggestive of a testicular location of HFMD, so no histological analysis was performed. However, the US examination did not show the typical signs of orchitis: increased size of the testis and increased vascularization at color Doppler [22]. The hypo-isoechoic mass-like area we found could have been caused by inflammation, fibrosis, or hematoma with infarcted seminiferous tubules.

Hurtt et al. [12] recently presented two similar cases of unilateral viral-induced testis masses. Both patients underwent orchiectomies because of a high level of anxiety over potential malignancy. Fortunately, both cases were negative for malignancy.

In order to avoid unnecessary invasive procedures, anamnesis should include recent upper respiratory or gastrointestinal infections.

Some authors claim that serological studies are not indicated routinely in epididymo-orchitis as they are unlikely to influence the management; whether radiological investigations are necessary is controversial [23]. Some authors recommend renal ultrasonography and cystography in every prepubertal case of acute epididymo-orchitis [24]: renal/bladder ultrasonography and cystourethrography for young boys (< 5 years) with epididymitis; and uroflowmetry, ultrasonography, and detailed questioning of voiding symptoms for older children (> 10 years).

Conclusion

HFMD is a typical childhood disease, but it may also occur in adults, which should be kept in mind because of the possibility of outbreaks. Viral epididymo-orchitis should be suspected in young men with a recent history of HFMD who present with testicular pain. It is important to recognize this unusual clinical presentation to avoid unnecessary invasive procedures or inappropriate antibiotic treatments.