Table of Contents  

Jabbr, Jaffar, Kassouma, and Salman: Localized leishmaniasis of the pharyngeal mucosa in the United Arab Emirates

Background

In most cases, mucosal leishmaniasis occurs as a consequence of cutaneous leishmaniasis. Here we present a case of leishmaniasis exclusively involving the pharyngeal mucosa but with possible paranasal sinus involvement, which is very rare. It was diagnosed in the United Arab Emirates (UAE), which is a non-endemic country, in an immunocompetent patient from Somalia, which is an endemic country for visceral leishmaniasis. We discuss the clinical presentation, diagnostic process and treatment for this patient.

Case presentation

A 51-year-old Somali man presented with the chief complaint of progressive dysphagia and a 2-year history of voice change but no known comorbidities. His medical history included chronic abdominal pain 1 month previously and gradual weight loss over the previous 6 months. His personal history revealed that he was neither a smoker nor an alcoholic; he denied any extramarital sexual relations or intravenous drug use, he had lived in Dubai for 20 years with no recent history of travel and was a driver by profession.

General examination revealed enlarged, tender right cervical lymph nodes, poor oral hygiene and no lesions/scars on the skin of his face, trunks or extremities, nor was there any history of a cutaneous lesion. His abdomen was soft with a palpable spleen. Flexible nasopharyngolaryngoscopy showed a nasopharyngeal mass extending to the orohypopharynx and saliva pooling in the pyriform fossa (Figures 1 and 2).

FIGURE 1

Flexible nasopharyngolaryngoscopy showing a nasopharyngeal mass. M, mass; SP, soft palate; TT, torus tubarius.

HMJ-641-fig1.jpg
FIGURE 2

Flexible nasopharyngolaryngoscopy showing an orohypopharyngeal mass and saliva pooling in the bilateral pyriform fossa and post-cricoid area. E, epiglottis; M, mass.

HMJ-641-fig2.jpg

The patient’s routine blood investigations revealed a normal full blood count, and elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR); viral markers, that is, human immunodeficiency virus (HIV), hepatitis B virus serum antigen and hepatitis C virus, were non-reactive. Computerized tomography (CT) of the naso-oropharynx showed a soft tissue mass involving the naso- and oropharynx, enlarged cervical lymph nodes, diffuse soft tissue filling the right maxillary sinus and bone erosion in its inferior wall (Figures 36). CT of the chest showed enlarged mediastinal and hilar lymph nodes, and bilateral apical fibronodular infiltrates; CT of the abdomen showed splenomegaly. Panendoscopy was performed and showed a soft tissue mass in the nasopharynx extending through the lateral pharyngeal walls to the oro- and hypopharynx; the vocal cords and oesophagus were normal.

FIGURE 3

CT image of the pharynx and paranasal sinuses (axial view).

HMJ-641-fig3.jpg
FIGURE 4

CT image of the pharynx (coronal view).

HMJ-641-fig4.jpg
FIGURE 5

CT image of the paranasal sinuses (coronal view).

HMJ-641-fig5.jpg
FIGURE 6

CT image of neck (axial view).

HMJ-641-fig6.jpg

Biopsies were taken from suspicious areas. A histology report revealed chronic inflammation with fibrosis and epithelial hyperplasia, but no evidence of an invasive malignancy. The patient was treated with oral antibiotics and discharged after his symptoms improved. Seven months later the patient returned complaining of the same symptoms of dysphagia and hoarseness. Examination revealed the same findings – a mass in the nasopharynx extending to the oropharynx and hypopharynx. Panendoscopy was performed and biopsies were taken from suspicious areas. Histology revealed chronic inflammation caused by predominantly lymphohistiocytic granulomas; no vasculitis, necrosis, fungi, parasites or micro-organisms were identified, and there was no definite evidence of malignancy. No specific pathological diagnosis was recognized as the symptoms were non-specific. The patient was again treated with intravenous antibiotics and was discharged following good improvement.

The patient was admitted to our department 8 months later with poor oral intake as a result of worsening dysphagia; examination showed the same mass in the nasopharynx extending to oropharynx and hypopharynx. The results of blood investigations revealed:

  • anaemia (haemoglobin 8 g/dl)

  • white blood cell count 2000 cells/ml3 (leucopenia)

  • platelets 65 000 cells/ml

  • ESR 53 mm/h

  • CRP 83 mg/dl

  • the presence of meticillin-resistant Staphylococcus aureus

  • normal liver function tests, urea and electrolytes, and thyroid function tests

  • cytomegalovirus DNA polymerase chain reaction (PCR) and the Treponema pallidum haemagglutination assay were negative

  • non-reactive VDRL (Venereal Disease Research Laboratory) test

  • non-reactive T-spot tuberculosis test

  • the absence of any pathogen in an acid-fast bacilli smear and culture.

Computerized tomography of the pharynx showed that the mass had increased in volume, extending from the nasopharynx to the hypopharynx with the same findings in the right maxillary sinus. Biopsies were taken from the suspicious areas by panendoscopy. The overall histomorphological features of the biopsies were suggestive of leishmaniasis, with the presence of Donovan bodies and Giemsa stains showing numerous Leishmania amastigotes with eccentric kinetoplasts filling the cytoplasm of the macrophages/histiocytes (Figure 7). We could not confirm the right maxillary sinus involvement by leishmaniasis disease because the patient refused further sinonasal endoscopy and biopsy. He was referred to an infectious diseases unit and was treated for pharyngeal leishmaniasis with amphotericin B, piperacillin/tazobactam and linezolid with good improvement, a decrease in the size of the mass and patent airways.

FIGURE 7

Microscopic examination (Giemsa stain × 400) showed numerous positive Leishmania amastigotes.

HMJ-641-fig7.jpg

However, flexible nasolaryngoscopy showed a new involvement of the vocal cords, predominantly on the left side, and possible disease involvement in the left sinus of Morgagni (Figure 8). Further CT of the chest, abdomen and pelvis showed possible diffuse splenomegaly and lung changes suggesting granulomatous disease. Abdomen ultrasound revealed a coarse liver with an irregular outline (suggesting underlying chronic liver disease), a bulky spleen and increased echo texture of both kidneys. The Leishmania antibodies titre was positive at 1 : 256. The patient refused further investigations despite hepatosplenomegaly and the pulmonary changes seen on the most recent CT scan, either because of a shortage of money or because he felt better after his initial therapy; however, the possibility of leishmaniasis in other sites could not be ruled out, especially after the positive Leishmania antibodies titre, which is primarily supportive of the presence of visceral leishmaniasis. He was discharged at his request after completion of treatment with significant improvement and given follow-up appointment with the infectious diseases clinic for laboratory investigations and abdomen ultrasound, an appointment with the ear, nose and throat clinic to reassess the new findings in the vocal cords and an appointment with the maxillofacial clinic for a paranasal sinus CT scan.

FIGURE 8

Flexible nasolaryngoscopy showed new involvement (arrows) of the vocal cords, predominantly on the left side, and possible disease involvement in the left sinus of Morgagni (star). E, epiglottis; LVC, left vocal cord; RVC, right vocal cord.

HMJ-641-fig8.jpg

Discussion

Leishmaniasis is caused by a Leishmania, a protozoan parasite of which there are more than 20 species, and which is transmitted to humans by the bite of infected female Phlebotominae sandflies.1,2 According to recent reports and Global Health Observatory data,3 leishmaniasis is endemic to more than 98 countries and territories. It is estimated that approximately 1.3 million new cases and 20 000–30 000 deaths occur annually.35 Leishmaniasis causes significant morbidity and mortality worldwide and its incidence has increased in recent years because of the growing number of patients with immune depression secondary to chronic illness, neoplasm, transplants and HIV infection, thereby constituting a public health problem.

In humans, there are three possible clinical forms of leishmaniasis: cutaneous, mucosal and visceral.6 However, mucosal and skin lesions may be noted concomitantly, which is known as mucocutaneous leishmaniasis. The term mucosal leishmaniasis traditionally refers to the metastatic sequelae of American cutaneous leishmaniasis, which results from the dissemination of parasites from the skin to mucous membranes of the upper respiratory tract, with lesions mainly in the nasal and oral mucosa and occasionally in the pharyngeal and laryngeal tissue, weeks or decades after the appearance of primary skin lesions. Some patients may also have subclinical skin lesions.2,7

Our patient reported no previous cutaneous lesions or immunosuppression. Thus, a diagnosis of localized leishmaniasis of the pharyngeal mucosa was established. However, mucosal involvement may be the first and only documentable pathological condition due to Leishmania.810 As a result of its heterogeneous presentation, mucosal leishmaniasis is often misdiagnosed and underestimated by clinicians and scientists, especially in the UAE, which is considered by the World Health Organization a non-endemic country as no any case of any type of leishmaniasis had been reported in the UAE up to the end of 2013.11

Diagnosis of leishmaniasis is based on endemicity, clinical symptoms and laboratory test results.12 In isolated pharyngeal leishmaniasis, the symptoms and pharyngeal lesions are not specific; in fact, they may mimic many inflammatory and neoplastic diseases. Diagnosis is usually further complicated by the absence of any documented history of cutaneous leishmaniasis, as in our case. Furthermore, considering the low incidence of this atypical localization, pharyngeal leishmaniasis is rarely suggested in differential diagnoses by physicians.13 Confirmation of suspected leishmaniasis requires laboratory tests. Histological evaluation of biopsies is usually able to confirm diagnosis, although it sometimes fails, as in our case, to detect Leishmania amastigotes. For this reason, physicians should inform the pathologist performing the histological examination about their suspicion so that samples can be stained with Giemsa’s stain; the presence of Leishman–Donovan bodies provides histological confirmation of the diagnosis.1416 Other examinations (e.g. leishmanin skin tests and the detection of anti-Leishmania antibodies) can only support diagnosis but PCR is a highly sensitive and specific molecular method of detecting the presence of Leishmania DNA and identifying the species.

The treatment approach for leishmaniasis depends, in part, on host and parasite factors. Some approaches and regimens are effective only against certain Leishmania species/strains and only in particular geographic regions. Pentavalent antimonial (Sbv) compounds such as sodium stibogluconate (Pentostam®, GlaxoSmithKline, London, UK) are the traditional mainstays in the treatment of leishmaniasis. Liposomal amphotericin B and miltefosine are also approved by the US Food and Drug Administration.17

Why did our patient exhibit isolated mucosal manifestations of leishmaniasis? Might this in fact represent secondary localization of the disease as a result of parasites in a dormant site elsewhere? The answer to these questions would be useful in reference to our patient, in whom the most recent CT demonstrated hepatosplenomegaly and pulmonary changes, which might be manifestations of visceral leishmaniasis, and who was positive for Leishmania antibodies. This is important because our patient is from Somalia, a country where, according to the World Health Organization, visceral leishmaniasis is endemic, so further investigations should be performed.18 Furthermore, a significant number of cases of visceral leishmaniasis have been reported among travellers in recent years.19,20 Camargo et al.21 discuss the clinical and CT features of 26 patients with mucosal leishmaniasis with involvement of the paranasal sinuses. The involvement of the maxillary sinus is often secondary to involvement of the lateral wall of the nose, which leads to blockage of the ostiomeatal complex. The soft-tissue thickening in the region of the right inferior and middle turbinates, and blockage of the middle meatal region seen on CT in our patient, might also point towards the likelihood of a similar pathogenesis.21

Conclusion

Leishmaniasis is rare in our country, and this is possibly the first case of its kind. It shows that physicians, when encountering a patient with the unusual presentation seen in our case, especially someone who has recently arrived from an endemic country, should have a high index of suspicion for leishmaniasis despite it being a rare disease. Ear, nose and throat doctors should remember this rare disease in the differential diagnosis of mucosal lesions to avoid an incorrect diagnosis and prevent inappropriate treatment. More research is needed to discover the mechanisms behind immunity to Leishmania in order to explain how pharyngeal leishmaniasis may occur, even in the absence of immune-compromising risk factors.

References

1. 

David CV, Craft N. Cutaneous and mucocutaneous leishmaniasis. Dermatol Ther 2009; 22:491–502. http://dx.doi.org/10.1111/j.1529-8019.2009.01272.x

2. 

Strazzulla A, Cocuzza S, Pinzone MR, et al. Mucosal leishmaniasis: an underestimated presentation of a neglected disease. BMC Res Int 2013; 1–7.

3. 

World Health Organization. Global Health Observatory Data Repository: Leishmaniasis. 2014. URL: http://apps.who.int/gho/data/node.main.NTDLEISH?lang=en (accessed 15 May 2014).

4. 

Salam N, Al-Shaqha WM, Azzi A. Leishmaniasis in the Middle East: incidence and epidemiology. PLOS Negl Trop Dis 2014; 8:e3208. http://dx.doi.org/10.1371/journal.pntd.0003208

5. 

lvar J, Velez ID, Bern C, et al. Leishmaniasis worldwide and global estimates of its incidence. PLOS ONE 2012; 7:e35671.

6. 

Francesca M, Maria CC, Vincenzo V. Ear, nose and throat manifestations of mucocutaneous leishmaniasis: a literature review. Acta Biomed 2014; 85:3–7.

7. 

World Health Organization. World Health Organization Working to Overcome the Global Impact of Neglected Tropical Disease. First WHO Report on Neglected Disease. Geneva: World Health Organization; 2010.

8. 

Aliaga L, Cobo F, Mediavilla JD, et al. Localized mucosal leishmaniasis due to Leishmania infantum clinical and microbiologic findings in 31 patients. Medicine 2003; 82:147–58. http://dx.doi.org/10.1097/01.md.0000076009.64510.b8

9. 

Berman JD. Human leishmaniasis: clinical, diagnostic, and chemotherapeutic developments in the last 10 years. Clin Infect Dis 1997; 4:684–703. http://dx.doi.org/10.1093/clind/24.4.684

10. 

Ngure P, Kimutai A, Tonui W, Ng’ang’a Z. A review of leishmaniasis in eastern Africa. Journal of Nanjing Medical University 2009; 23:79–86.

11. 

World Health Organization. Status of Endemicity of Cutaneous Leishmaniasis Data by Country. 2014. URL: http://apps.who.int/gho/data/node.main.NTDLEISHCEND?lang=en (accessed 15 May 2014).

12. 

Reithinger R, Dujardin JC. Molecular diagnosis of leishmaniasis: current status and future applications. J Clin Microbiol 2007; 45:21–5. http://dx.doi.org/10.1128/JCM.02029-06

13. 

Lessa MM, Lessa HA, Castro TW, et al. Mucosal leishmaniasis: epidemiological and clinical aspects. Rev Bras Otorrinolaringol 2007; 73:843–7. http://dx.doi.org/10.1590/S0034-72992007000600016

14. 

Singh S. New developments in diagnosis of leishmaniasis. Indian J Med Res 2006; 123:311–30.

15. 

Cocuzza S, Strazzulla A, Pinzone MR, et al. Isolated laryngeal leishmaniasis in immunocompetent patients: an underdiagnosed disease. Case Rep Infect Dis 2013; 2013:1–7.

16. 

World Health Organization. Report of a Meeting of the WHO Expert Committee on the Control of Leishmaniasis. Geneva, Switzerland: World Health Organization; 2010.

17. 

Nashan D. Leishmaniasis. J German Soc Dermatol 2015; 13:191–201.

18. 

World Health Organization. Status of Endemicity of Visceral Leishmaniasis Data by Country. 2014. URL: http://apps.who.int/gho/data/node.main.NTDLEISHVEND?lang=en (accessed 15 May 2014).

19. 

Mansueto P, Seidita A, Vitale G, Cascio A. Leishmaniasis in travelers: a literature review. Travel Med Infect Dis 2014; 12:563–81. http://dx.doi.org/10.1016/j.tmaid.2014.09.007

20. 

Perez-Ayala A, Norman F, Perez-Molina JA, Herrero JM, Monge B, Lopez-Velez R. Imported leishmaniasis: a heterogeneous group of diseases. J Travel Med 2009; 16:395–401. http://dx.doi.org/10.1111/j.1708-8305.2009.00341.x

21. 

Camargo RA, Tuon FF, Sumi DV, et al. Mucosal leishmaniasis and abnormalities on computed tomographic scans of paranasal sinuses. Am J Trop Med Hyg 2010; 83:515–18. http://dx.doi.org/10.4269/ajtmh.2010.10-0081




Add comment 





Home  Editorial Board  Search  Current Issue  Archive Issues  Announcements  Aims & Scope  About the Journal  How to Submit  Contact Us
Find out how to become a part of the HMJ  |   CLICK HERE >>
© Copyright 2012 - 2013 HMJ - HAMDAN Medical Journal. All Rights Reserved         Website Developed By Cedar Solutions INDIA