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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 9  |  Issue : 3  |  Page : 322-324

Isolated testicular tuberculosis with ethambutol cutaneous toxicity: A combination of two rare entities


1 Department of Internal Medicine, Centro Hospitalar do Baixo Vouga, Aveiro, Portugal
2 Department of Pulmonology, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal

Date of Submission26-Jun-2020
Date of Decision01-Jul-2020
Date of Acceptance03-Jul-2020
Date of Web Publication28-Aug-2020

Correspondence Address:
Flávio Godinho Pereira
Internal Medicine Department, Centro Hospitalar do Baixo Vouga, AAvenida Doutor Artur Ravara, 3810 193 Aveiro
Portugal
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmy.ijmy_114_20

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  Abstract 


Tuberculosis (TB) is an infection that can affect any organ, affecting mainly the lungs. Isolated testicular TB is very rare. Six months of a multiple drug scheme is the mainstay of TB treatment. Adverse reaction to anti-TB chemotherapy is frequent and affects the course of the therapy, leading sometimes to discontinuation of drugs. Ethambutol optic nerve toxicity is frequent. However, severe cutaneous and anaphylactic reactions associated to ethambutol are very rare. We present the case of an immunocompetent patient presenting with isolated testicular TB that exhibited a severe cutaneous and anaphylactic reaction to ethambutol during the consolidation treatment phase. This led to exhaustive etiologic study and treatment modification.

Keywords: Cutaneous toxicity, ethambutol, extrapulmonary tuberculosis, testicular tuberculosis


How to cite this article:
Pereira FG, Leal Md, Cavadas S, Ladeira I. Isolated testicular tuberculosis with ethambutol cutaneous toxicity: A combination of two rare entities. Int J Mycobacteriol 2020;9:322-4

How to cite this URL:
Pereira FG, Leal Md, Cavadas S, Ladeira I. Isolated testicular tuberculosis with ethambutol cutaneous toxicity: A combination of two rare entities. Int J Mycobacteriol [serial online] 2020 [cited 2020 Oct 26];9:322-4. Available from: https://www.ijmyco.org/text.asp?2020/9/3/322/293539




  Introduction Top


Extrapulmonary tuberculosis (EPTB) accounts for around 10%–15% of total cases of tuberculosis (TB). Genitourinary TB (GUTB) is the second most common form of EPTB, accounting for 8%–15% of EPTB.[1],[2],[3] Testicular TB is rare, accounting for only 3% of GUTB.[4],[5]

The treatment of GUTB comprises the standard anti-TB treatment scheme.[4] Ethambutol's optic nerve toxicity has been extensively studied. However, cutaneous toxicity is rare, and only a few cases of severe cutaneous reactions leading to its discontinuation have been described.[6],[7]

We report the case of an immunocompetent adult with isolated testicular TB, who exhibited a severe cutaneous reaction due to ethambutol.


  Case Report Top


We describe the case of a 48-year-old South African male that presented with painful, right-sided testicular swelling for 2 months. There was no history of local inflammatory signs, respiratory, urinary, or constitutional symptoms. He was living in Portugal for the past 30 years, but he had been in South Africa for 2 weeks, 2 years before presentation. His past medical history was unremarkable. On physical examination, a right nontender testicular mass was palpable. Ultrasonography of the testicles revealed a solid, vascularized lesion adjacent to the right epididymis. The patient underwent surgical resection of the lesion.

Anatomopathological examination revealed inflammatory cell infiltrate and multiple epithelioid granulomas with central necrosis (the piece was not sent for mycobacterial culture). Both Ziehl–Neelsen staining and GeneXpert Mycobacterium TB (MTB)/Realtime polymerase chain reaction (RIF PCR) assay were negative in the piece. Additional investigation for mycobacteria (sputum and urine sample culture) and HIV testing were negative. Thoracic computed tomography was normal.

Probable testicular TB was assumed. The patient started anti-TB scheme with rifampin, isoniazid, pyrazinamide, and ethambutol. He underwent intensive treatment for 2 months without any side effects. Consolidation treatment included rifampicin, isoniazid, and ethambutol. One month after the beginning of the consolidation phase, the patient developed a diffuse, prickly, maculopapular rash, initially limited to the abdomen, inguinal region, and upper limbs. Despite treatment with antihistamine drugs, the rash became generalized, sparing only the head. He also developed swelling of both legs and tongue. The rash evolved to desquamative lesions. The patient never revealed bullous lesions or gastrointestinal symptoms. Drug hypersensibility was suspected. The patient was sent for an immunoallergology evaluation, and all anti-TB drugs were suspended. Following suspension, all symptoms improve 3 days later. He underwent provocation tests to rifampicin and isoniazid, which were normal and restarted these drugs. One week later, he restarted ethambutol, and 1 h after taking it, he developed a generalized rash, conjunctival hyperemia, pharyngeal constriction, dysphagia, and dysphonia. He presented to the emergency room and an anaphylactic reaction with cutaneous reaction was diagnosed. Both reactions were attributed to ethambutol.

The patient continued rifampicin and isoniazid. Ethambutol was replaced with levofloxacin for the next 6 months. No further complications were reported.


  Discussion Top


Clinical presentation of testicular TB is very unspecific, ranging from scrotal pain or skin ulceration to palpable untender mass. Clinical manifestations often present with long latent period from the primary infection, ranging from 5 to 40 years.[2] Testicular infection can happen due to two mechanisms: hematogenous spreading of lung infection or transurethral reflux.[1],[3],[8],[9] There is multiple differential diagnosis, including bacterial epididymitis, epididymal sperm granuloma, or tumor.[3],[8]

The gold standard for diagnosing TB is isolation of MTB in patient's tissues or fluids. However, this is not always possible, especially in EPTB. Anatomopathological examination can help diagnosing when the findings are epithelioid granulomas with central necrosis (suggestive of TB), such as presented in our case.[8],[9] Isolation of MTB is hard when the surgical piece is not sent for mycobacterial culture. Molecular testing has improved the diagnostic yield, but it is not 100% sensitive nor specific. Definite diagnosis is not always possible, and treatment can be started when the diagnosis is deemed probable.

Over 60% of patients with testicular TB undergo surgery due to delay in the diagnosis and neoplastic disease possibility, like it happened in our case.[1],[2],[5],[8] An earlier diagnosis and initiation of chemotherapy could had avoided such surgery. Nonetheless, surgery is important when the anamnesis is not suggestive of TB and a neoplastic etiology cannot be ruled out. Six months of chemotherapy is standard duration in most EPTB. Given that we were unable to isolate the bacilli and obtain an anti-TB drug sensitivity test, we decided to prolong the ethambutol treatment into the consolidation phase, to ensure a minimum risk of treatment failure.[2]

Cutaneous rashes are very frequent in patients taking anti-TB drugs, with an incidence of over 8%. However, ethambutol rarely causes rash, occurring in only 0.5% of patients.[10],[11] This kind of reaction is more frequently associated with isoniazid or rifampicin.[10] This kind of reaction is more frequently associated with isoniazid or rifampicin.

In our case, we highlight that all lesions disappeared after the drugs were suspended. After the sequential reintroduction of isoniazid and rifampicin, the patient remained asymptomatic. Finally, after only 1 h of restarting ethambutol, the patient developed a severe cutaneous and anaphylactic reaction. These findings support our conclusion that the initial skin reaction was associated with ethambutol. Cutaneous toxicity has been very rarely associated with ethambutol, making this case one of the few cases described in literature. To our knowledge, there are two described cases: (1) a 39-year-old woman who presented with a pruritic, eczematous exanthema on the trunk and forearms and a drug reaction with eosinophilia and systemic symptoms syndrome due to ethambutol was diagnosed; (2) a 30-year-old woman presenting with diffuse maculopapular pruritic rash on the trunk and extremities, where drug-induced hypersensitivity syndrome due to ethambutol was assumed.[6],[7]

GUTB should be a differential diagnosis in patients with testicular masses that are from high incidence countries, even if they have not been there for more than 20 years, due to the long latent period. Molecular biology testing has improved the accuracy of this diagnosis, but clinical suspicion continues to be important to make the diagnosis.[9] Early diagnosis and start of anti-TB drugs can avoid surgical excision and the appearance of late complications. Anti-TB chemotherapy may have several toxicities. Patients need to be closely monitored in order to diagnose them early, identify the offending agent, and discontinue it. This latter step is not always linear due to the multidrug scheme necessary in TB.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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2.
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Ramos JM, Isea-Peña MC, Tesfamariam A, Balcha S, Reyes F, Górgolas M. Mammary, testicular and adnexal tuberculosis diagnosed by histology in a rural hospital in Southern Ethiopia. Int J Mycobacteriol 2012;1:212-4.  Back to cited text no. 3
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Bedi N, Rahimi MNC, Menzies S, Kalsi J. Atypical testicular pain. BMJ Case Rep 2019;12:e226697. doi:10.1136/bcr-2018-226697.  Back to cited text no. 5
    
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Yoshioka Y, Hanafusa T, Namiki T, Nojima K, Amano M, Tokoro S, et al. Drug-induced hypersensitivity syndrome by ethambutol: A case report. J Dermatol 2016;43:971-2.  Back to cited text no. 6
    
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Gest N, Ingen-Housz-Oro S, Gener G, Bellanger M, Henn A, Gallien S, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome due to ethambutol. Med Mal Infect 2018;48:302-5.  Back to cited text no. 7
    
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Man J, Cao L, Dong Z, Tian J, Wang Z, Yang L. Diagnosis and treatment of epididymal tuberculosis: A review of 47 cases. PeerJ 2020;8:e8291.  Back to cited text no. 8
    
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Kapoor R, Ansari MS, Mandhani A, Gulia A. Clinical presentation and diagnostic approach in cases of genitourinary tuberculosis. Indian J Urol 2008;24:401-5.  Back to cited text no. 9
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Castro AT, Mendes M, Freitas S, Roxo PC. Incidence and risk factors of major toxicity associated to first-line antituberculosis drugs for latent and active tuberculosis during a period of 10 years. Rev Port Pneumol (2006) 2015;21:144-50.  Back to cited text no. 10
    
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Cernadas JR, Santos N, Pinto C, Mota PC, Castells M. Hypersensitivity reaction and tolerance induction to ethambutol. Case Rep Med 2013;2013:208797.  Back to cited text no. 11
    




 

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