Unmasking immune reconstitution inflammatory syndrome: a report of tuberculous epididymo-orchitis mimicking a testicular tumour in a Caucasian AIDS patient

Introduction

Tuberculosis (TB) is a leading killer of people living with HIV causing one in three HIV deaths. ¹ Worldwide, it is estimated that 14.8% of all new TB cases in adults are attributable to HIV infection. ²

Genitourinary TB (GUTB) is not common and it is considered a severe form of extrapulmonary TB. ³ However, due to recent surge in the prevalence of TB worldwide linked to HIV pandemic has resulted in a concomitant increase in extrapulmonary TB of which GUTB accounts for up to 20% in endemic areas. ⁴ Many cases coexist with pulmonary TB or TB of other parts of lower genitourinary system including bladder, ureter, and prostate. ⁵ Isolated tuberculous epididymo-orchitis is rare.

Here, we report a Caucasian HIV seropositive patient with a clinical diagnosis of testicular tumour who underwent a right orchidectomy. The histopathology report revealed tuberculous epididymo-orchitis.

Case report

A 46-year-old heterosexual Caucasian man presented with a history of tiredness to our genitourinary clinic. He denied history of weight loss, night sweats, or testicular pain. He lived in Thailand for few years and had several female sexual partners whilst living there. He was offered a full sexually transmitted infections (STIs) screen including an urgent HIV test. The latter was positive. His nadir CD4 count was 84 cells/mm³ (5%) and HIV viral load 6.54 × 10⁵IU/ml. Laboratory data revealed a white blood cell count of 5.6 × 10⁹/l, haemoglobin concentration of 13.7 g/l, CRP 23 mg/l. The chest radiography was normal (Figure 1(a)). The patient was commenced on combination of Truvada (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg), darunavir 800 mg and ritonavir 100 mg once daily. OPEN IN VIEWER

A month later, he was admitted to a local hospital with symptoms of fever and diarrhoea. The laboratory data showed an elevated CRP of 191 mg/l, haemoglobin concentration of 10.8 g/l, a white blood cell count of 4.8 × 10⁹/l. Blood and stool cultures were negative for TB. A repeat chest radiograph revealed changes which could represent lymphadenopathy (Figure 1(b)). The latter was not evaluated any further and he was discharged home on oral antibiotics.

Twelve weeks after starting anti-retroviral therapy (ART), he presented with a right painful testicular lump to his general practitioner. A presumptive diagnosis of bacterial epididymo-orchitis was made and he was given oral antibiotics. An urgent scrotal ultrasound was arranged which reported a large right testicular hypoechoic mass consistent with a testicular tumour. He was urgently referred to urology team and he underwent a right orchidectomy. During this time, the patient did not seek any medical advice from our HIV team.

Histopathology results showed a florid granulomatous epididymo-orchitis associated with foci of more acute epididymitis and tubular rupture. Ziehl–Neelsen stain on tissue sections showed acid-fast bacilli (AFB) positivity (Figures (2) to (4)). OPEN IN VIEWER

Two weeks following surgery, he presented with enlarged left supraclavicular and anterior cervical lymph nodes. Ultrasound scan of the patient’s neck revealed multiple necrotic lymph nodes of varying sizes consistent with tuberculous lymphadenitis. Antiretroviral therapy was changed to Truvada (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg), efavirenz 600 mg daily and he was commenced on anti-tuberculous chemotherapy. OPEN IN VIEWER

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Figure 4.

Section of the epididymis showing granulomatous inflammation.

Discussion

TB is a bacterial infection caused by Mycobacterium tuberculosis. It is transmitted by coughed droplet and usually presents with respiratory symptoms. However, it can infect any organ and miliary TB is sometimes reported, these manifestations are less frequent in immunocompetent patients. Dissemination from the site of initial infection in the lung can take place at the time of primary infection or years later, when immunologic containment fails, immunosuppression particularly due to HIV infection increases the risk of reactivation and unusual presentations of TB as in our patient.^6,7

Few cases of tuberculous epididymo-orchitis in HIV patients have been reported.^8–11 All patients were from developing countries where TB is a common opportunistic infection. To the best of our knowledge, this is the first reported case of AIDS presenting as tuberculous epididymo-orchitis in a Caucasian patient.

Immune Reconstitution Inflammatory Syndrome (IRIS) may occur in response to many pathogens. IRIS commonly occurs in association with Mycobacterium tuberculosis, Mycobacterium avium complex (MAC), cytomegalovirus (CMV), and Cryptococcus, and it may occur with Pneumocystis, Toxoplasma, hepatitis B and C, human herpes virus 8 (HHV-8, which causes Kaposi sarcoma), and JC virus (which causes progressive multifocal leukoencephalopathy).

TB associated IRIS is a frequent early complication of ART which reflects an immunopathological reaction to mycobacterial antigens as a result of the recovering immune system. Unmasking TB-IRIS describes patients with unrecognized TB at ART initiation, who present with an exaggerated inflammatory presentation of TB during early ART. ¹² The minimum criteria required to diagnose IRIS are (a) temporal association between initiation of ART and subsequent development of symptoms (usually within three months), (b) evidence of immune restoration (decrease in plasma HIV RNA level by more than 1 log 10 copies/ml and an increase in CD4 count from baseline), and (c) clinical symptoms and signs consistent with an inflammatory process. ¹³ Our patient had advanced HIV disease with a viral load of 6.54 × 10⁵IU/ml and low CD4 count 84 (5%) at the initiation of ART. The paradoxical worsening and the presentation, with an opportunistic infection 12 weeks after the initiation of highly active anti-retroviral therapy, correlated with the drop in viral load to 155 IU/ml and the rise in CD4 count to 108 (7%). In this patient, all three criteria were met and hence it is IRIS.

Although this patient had fever and chest X-ray changes few weeks prior to developing epididymo-orchitis, and the fact he was known to be HIV-positive, TB epididymo-orchitis was not considered in the differential diagnosis of a scrotal swelling when he was evaluated by urology team, this is undoubtedly due to the rarity of this case.

In an AIDS patient presenting with a scrotal swelling, the clinical differential diagnosis should include: herpes simplex virus, varicella-zoster virus, and CMV infections; syphilis chancroid; deep fungal infections; TB; and atypical mycobacterial infections, as well as neoplastic causes such as squamous cell carcinoma, lymphoma, and Kaposi sarcoma.

We want to convey the message that in HIV-positive patients presenting with testicular swelling, with a history of living in an endemic area of TB, an infective aetiology should be considered. This will increase the possibility of early diagnosis, as well as proper and timely management.