Case Report: A Rare Case of Crimean–Congo Hemorrhagic Fever Associated with Epididymo-Orchitis

ABSTRACT

Crimean–Congo hemorrhagic fever (CCHF) is an acute infectious disease that affects multiple organ systems and is characterized by extensive ecchymosis, internal hemorrhage, and hepatic dysfunction. The reported case fatality rate varies between 8% and 80%. It is frequently transmitted by Hyalomma ticks, which are endemic in the Northeast Anatolia region of Turkey in spring and summer. Our patient presented from an endemic area with fever, malaise, joint pain, and scrotal pain following a tick bite, and real-time PCR analysis of venous blood was positive for CCHF. Based on Doppler ultrasound performed because of the patient’s scrotal pain, he was diagnosed as having epididymo-orchitis, which was considered secondary to CCHF after ruling out other etiologies and resolved with scrotal elevation and anti-inflammatory treatment. Being a very rare complication, this report aimed to document this case of CCHF-associated epididymo-orchitis in the literature.

INTRODUCTION

Crimean–Congo hemorrhagic fever (CCHF) is endemic in the Northeast Anatolia region of Turkey in spring and summer. It presents with sudden-onset fever, malaise, extensive myalgia and arthralgia, headache, and sore throat.¹ These symptoms are sometimes accompanied by nausea, vomiting, abdominal pain, and watery diarrhea.² Because CCHF causes endothelial damage, it may manifest with clinical signs and symptoms in highly vascularized organs.³ Here, we present a very rare case of epididymo-orchitis as a complication of CCHF.

CASE PRESENTATION

A 51-year-old man presented to our emergency department with fever, malaise, joint pain, and scrotal pain that developed after removing a tick from his leg 3 days earlier. He had worked in animal husbandry for 20 years and had no history of known diseases or regular medication. On physical examination, his body temperature was 38.5°C, and heart rate was rhythmic and 82 beats/minute, and he exhibited conjunctival hyperemia and extensive maculopapular rash on his body. In addition, his right scrotal area showed mild edema, sensitivity to touch, and a mild rash (Figure 1). His laboratory results (and limits of the normal range) were as follows: white blood cell count: 3,300 mm³/L (3,910–10,900 mm³/L), hemoglobin: 12.4 g/dL (14.1–17.8 g/dL), platelet count: 126,000 mm³/L (152,000–383,000 mm³/L), aspartate aminotransferase (AST): 44 U/L (13–40 U/L), alanine aminotransferase (ALT): 41 U/L (7–49 U/L), lactate dehydrogenase (LDH): 456 U/L (120–246 U/L), creatine phosphokinase: 70 U/L (46–171 U/L), active partial thromboplastin time: 32.3 seconds (24–36 seconds), erythrocyte sedimentation rate: 37 mm/hour, and amylase: 143 U/L (30–118 U/L). Because the patient had presented to our emergency department from a region endemic for CCHF and because of his history of tick exposure 3 days earlier, venous blood real-time PCR analysis was performed for CCHF, and the result was positive. On Doppler ultrasound performed because of his scrotal pain, his left and right testes were measured as 42 × 23 mm and 55 × 28 mm, respectively. There was a marked increase in blood flow in the right side of the scrotum compared with the left (Figure 1). On consultation by the urology clinic to determine the etiology of his epididymo-orchitis, it was determined that the patient had no suspicious sexual contact or medication history. Urine PCR tests for the common etiological factors Chlamydia, Neisseria gonorrhoeae, and Trichomonas vaginalis yielded negative results. Brucella agglutination test was negative, as were the venereal disease research laboratory test for syphilis and HIV antibody test. Interferon gamma release assay for tuberculosis was also negative. His mumps IgG test result was positive, whereas IgM was negative. Scrotal elevation and anti-inflammatory treatment were prescribed as treatment for epididymo-orchitis. On day 7 of follow-up, a CCHF IgM test result was positive. After ruling out the usual etiologies, epididymo-orchitis secondary to CCHF was suspected. Supportive treatment was provided, but ribavirin was not added. After the patient’s laboratory parameters normalized and clinical signs resolved, the symptoms of epididymo-orchitis also regressed, and the patient was discharged with follow-up.

Figure 1.

At presentation, the patient’s right scrotal area showed mild edema, sensitivity to touch, and a mild rash, and was increased in size compared with the left side, particularly at the right epididymal tail. On Doppler ultrasound, the right epididymis and testis showed a heterogeneous parenchyma structure with a significant increase in blood flow relative to the left side. This figure appears in color at www.ajtmh.org.

DISCUSSION

Crimean–Congo hemorrhagic fever manifests with sudden fever, weakness, diffuse myalgia and arthralgia, headache, and sore throat. These symptoms are sometimes accompanied by complaints of nausea, vomiting, abdominal pain, and watery diarrhea. Early signs may include hypotension, conjunctival hyperemia, and blanching macular rash.³ It can present with fever and hemorrhage and may lead to shock and death in severe cases. Coagulation and fibrinolysis in CCHF manifest clinically as petechiae, ecchymosis, mucosal bleeding, and uncontrollable hemorrhage at sites of venipuncture.⁴ Monocytes, endothelial cells, and hepatocytes are the main targets in CCHF. The resulting vascular damage induces clotting dysfunction and increased endothelial permeability, which lead to hemorrhagic diathesis. Inflammatory mediators play a major role in fatal cases.⁵

Infection with the CCHF virus has four different phases: incubation, pre-hemorrhagic, hemorrhagic, and convalescence. Incubation time varies between 2 and 9 days. After the incubation period, the pre-hemorrhagic phase is characterized by sudden-onset fever, influenza-like symptoms, and neuropsychiatric and cardiovascular changes. Our patient had a history of tick bite before the onset of fever, malaise, scrotal pain, and myalgia. Hepatomegaly and splenomegaly may also be observed.⁶ Thrombocytopenia is generally seen in CCHF. Patients have been reported to have leukopenia and high levels of AST, ALT, LDH, and creatine phosphokinase.⁷ The present case was considered consistent with CCHF because of the history of tick bite, thrombocytopenia, leukopenia, and high levels of creatinine phosphokinase and LDH. The patient also tested positive for CCHF virus IgM. Supportive care is the mainstay of treatment, and includes maintaining fluid and electrolyte balance and providing thrombocyte, fresh frozen plasma, and erythrocyte replacement. Ribavirin is the only antiviral drug used in CCHF.⁸ Our patient was followed up with supportive care alone, but ribavirin was not used.

Patients with acute epididymo-orchitis typically present with intense scrotal pain, swelling, tenderness, and fever. Viral orchitis is associated with sudden-onset scrotal pain and swelling and is initially unilateral. Our patient had unilateral scrotal pain and swelling on the third day after admission. Doppler US is an important diagnostic modality in epididymo-orchitis.⁹ Scrotal Doppler ultrasonography in our patient was consistent with epididymo-orchitis, and combined with physical examination, epididymo-orchitis was suspected. Our patient did not have any history of sexually transmitted disease. The results of bacterial and viral pathogen tests performed for the differential diagnosis of epididymo-orchitis were negative. There were no findings suggesting tuberculosis in the etiology, and the result of interferon gamma release assay was negative. No microorganisms other than CCHF virus were isolated during testing, and no drugs or diseases that cause epididymo-orchitis were detected.

The treatment of epididymo-orchitis includes bed rest, scrotal elevation, analgesics, anti-inflammatory drugs, and antibiotics if infection is suspected. Antibacterial drugs are not indicated for the treatment of viral orchitis, and the condition spontaneously improves after 3–10 days.¹⁰ In our patient, nonsteroidal anti-inflammatory medication, scrotal elevation, and bed rest were used as symptomatic treatment for epididymo-orchitis.

Crimean–Congo hemorrhagic fever shows more severe involvement of the bone marrow, spleen, lymph nodes, and liver, where the reticuloendothelial system is more active. The impact of bone marrow involvement on hematologic parameters, as well as the direct viral effect on the vascular endothelium, can result in a more severe clinical course. The lesser presence of the reticuloendothelial tissue in the testicles than that of the aforementioned organs may explain why epididymo-orchitis occurs infrequently with CCHF. However, the extensive vasculature of the epididymis combined with the high virulence of CCHF virus may make this tissue a potential target of infection.

Our search of the literature yielded only one previous case, which was also from the endemic Northeast Anatolia region of Turkey.¹¹ As in the earlier case, our patient responded well to symptomatic anti-inflammatory therapy and scrotal elevation, and his complaints resolved with regression of the other signs and symptoms of CCHF. We sought to contribute to the literature with this case, as epididymo-orchitis is an extremely rare complication of CCHF.