Orofacial manifestations of mucocutaneous leishmaniasis: a case series from Brazil

Gleicy Gabriela Vitória Spinola Carneiro  Falcão; Liliane Lins-Kusterer; Patricia Miranda Leite-Ribeiro; Viviane Almeida Sarmento

doi:10.12688/f1000research.19056.2

Home Browse Orofacial manifestations of mucocutaneous leishmaniasis: a case series...

ALL Metrics

Views

Downloads

Get PDF

Get XML

Export

▬

✚

Clinical Practice Article

Revised

Orofacial manifestations of mucocutaneous leishmaniasis: a case series from Brazil

[version 2; peer review: 1 approved, 1 approved with reservations]

Gleicy Gabriela Vitória Spinola Carneiro Falcão¹, Liliane Lins-Kusterer¹, Patricia Miranda Leite-Ribeiro¹, Viviane Almeida Sarmento ¹

PUBLISHED 16 Apr 2020

Author details Author details

¹ Professor Edgard Santos Hospital, Federal University of Bahia, Salvador, BA, 40110060, Brazil

Gleicy Gabriela Vitória Spinola Carneiro Falcão
Roles: Investigation, Writing – Original Draft Preparation

Liliane Lins-Kusterer
Roles: Conceptualization, Writing – Review & Editing

Patricia Miranda Leite-Ribeiro
Roles: Investigation, Writing – Review & Editing

Viviane Almeida Sarmento
Roles: Conceptualization, Supervision, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

This article is included in the Neglected Tropical Diseases collection.

Abstract

The dental surgeon plays a fundamental role in the early diagnosis of oral leishmaniasis. Although these lesions are rare at oral mucosa, this is one of the manifestations sites of the disease This study reports seven clinical cases of orofacial mucocutaneous leishmaniasis. All had mucocutaneous leishmaniasis confirmed by laboratory tests, with orofacial involvement. Five out of the seven cases were males, and in four cases, patients had associated comorbidities. Late diagnosis was observed, resulting in treatment delay and increased hospitalization stay. One patient had severe psychological consequences due to facial deformity. The lack of differential diagnosis due the great variability of clinical presentation of the lesions and frequent unspecific histopathology represent a challenge for the dental surgeon. In two reported cases, there were unspecific biopsy results. This series of cases highlights the importance of a multidisciplinary approach in the diagnosis and treatment of oral and perioral leishmaniasis. Patients with atypical lesions, originating from or living in endemic regions, should be investigated for leishmaniasis. These procedures could avoid delays in diagnosis and decrease the risk of disease dissemination.

Keywords

Leishmaniasis, Mucocutaneous, Diagnosis, Oral, Dental Care

Corresponding author: Viviane Almeida Sarmento

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2020 Falcão GGVSC et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Falcão GGVSC, Lins-Kusterer L, Leite-Ribeiro PM and Sarmento VA. Orofacial manifestations of mucocutaneous leishmaniasis: a case series from Brazil [version 2; peer review: 1 approved, 1 approved with reservations]. F1000Research 2020, 8:756 (https://doi.org/10.12688/f1000research.19056.2) First published: 29 May 2019, 8:756 (https://doi.org/10.12688/f1000research.19056.1) Latest published: 24 Sep 2020, 8:756 (https://doi.org/10.12688/f1000research.19056.4)

Revised Amendments from Version 1

Abstract

We emphasize that although these lesions are rare in the oral mucosa, it cannot be ruled out as a differential diagnosis, considering mainly, when such lesions occur in endemic regions as all reported cases.
We emphasize the orofacial involvement in our case reports.
And so, the dentist becomes essential to the early diagnosis of these lesions, thus preventing the spread of the disease and need to be familiarized with this type of manifestations of this infectious disease related to their care practice.

Introduction

We have corrected typos

Case Reports

Pertinent information about the reported cases was added, such as the absence of infections or pre-existing comorbidities that could confuse the diagnosis.

Discussion
- We discuss included studies.
- We have added a paragraph in the discussion in which the literature was updated with the introduction of three new references, which discuss the treatment, mainly concerning the local treatment of the lesion, which is already used in some centers but has yet to be proven effective.

Conclusions:
- We restructured and shortened the conclusion, to allow for greater understandability.

References:

We have added three new updates references.

See the authors' detailed response to the review by Braulio Valencia

Introduction

Leishmaniasis is a parasitic disease caused by several species of the protozoan genus Leishmania¹. It is a widely dispersed disease, being endemic in 98 countries, including Brazil. Leishmaniasis classification encompasses different clinical forms²; mucocutaneous leishmaniasis is a chronic form of infection³ that may manifest in the mucosa after months or years of latency⁴.

The mucosal involvement of leishmaniasis is uncommon, mainly in immunocompetent individuals⁵. The lymphatic or hematogenous dissemination of amastigotes may occur from the skin to the nasal, oropharyngeal, laryngeal and/or tracheal mucosa. Delayed diagnosis^3,6 and development of primary lesion in the oral mucosa and in the head and neck region can cause dysphagia, dysphonia and dyspnoea³.

The diagnosis of mucocutaneous leishmaniasis can be difficult⁷. In older lesions, few parasites are usually detected by microscopy or culture and the clinical aspect may resemble neoplasia^1,8. Orofacial symptoms depend on the localization of the lesions and may include nasal obstruction, difficulties in swallowing, mucosal bleeding and/or hoarseness⁸. Destructive lesions of the mucosa contain few parasites, with high levels of tumor necrosis factor (TNF) suggesting an unmodulated immune response with increased production of proinflammatory cytokines responsible for tissue damage⁹.

In this study we report seven clinical cases of orofacial mucocutaneous leishmaniasis from Brazil.

Case reports

This study included seven patients admitted to Edgard Santos University Hospital, Federal University of Bahia, Brazil. All patients had a confirmed diagnosis of mucocutaneous leishmaniasis with oropharyngeal involvement and no visceral involvement, confirmed by laboratory tests. This study was approved by the Ethics and Research Committee of Edgard Santos University Hospital, CAAE 93381518.7.000.0049. All patients (or parents/guardians) provided written informed consent for the publication of their medical data and images.

Case 1

Male, 24-years-old, Caucasian, unemployed, from Tancredo Neves, State of Bahia, Brazil, was admitted to the University Hospital, in January 2012, presenting diffuse bullous lesions on the body, osteoarthritis of the distal interphalangeal joints and proteinuria 399 mg/day (reference value >150mg/day). He was diagnosed with systemic lupus erythematosus (SLE) and treated with mycophenolate mofetil (MMF). The starting dose for MMF was 0.5 g per day and it was increased up to 1 g per day intravenously. In 2014, two years after SLE diagnosis, he was hospitalized, presenting with ulcerated-painless-skin lesions on the face, upper lip, scalp, neck, upper and lower limbs. Oral examination evidenced crusty upper lip lesions, poor oral health status and amelogenesis imperfecta (Figure 1a and 1b). He developed secondary infection associated with fever, and antibiotic therapy with cephalexin was initiated (1g/day) and a maintenance dose of prednisone (5 mg/day intravenously). On the third day, biopsies were performed on the left nasal mucosa and on the right lower limb lesions. The diagnosis of disseminated leishmaniasis was confirmed (positive PCR and Montenegro intradermal test). Liposomal amphotericin B was introduced on the fourth day of hospitalization at a dose of 150 mg/day up to a maximum dose of 2,400 mg. The patient treatment was followed-up for six months, and lesions were observed to have healed. One month later, during the follow-up for SLE, we observed new development of ulcerated skin lesions on the face and on the upper and lower right limbs. Blisters and fever were absent and the recurrence of disseminated leishmaniasis was confirmed. Few weeks later, the patient was admitted for treatment of new lesions, presenting with erythema, diffuse facial edema, lymphadenopathy and ulcerated and pustular lesions. Patient was treated with liposomal amphotericin B at a cumulative dose of 3,050 mg and followed-up until complete remission of the lesions. Currently, patient is under maintenance treatment for SLE.

Figure 1.

Oral examination evincing poor oral health status and amelogenesis imperfecta reported at Case-1 (a and b); Infiltrative lesion on hard, soft palate and uvula reported at Case-2 (c); Ulcerated lesions in the lower lip frenulum, reported at Case-3 (d).

Case 2

In July 2013, 53-year-old male, Caucasian, unemployed, from Mundo Novo, State of Bahia, Brazil, attended to the Stomatology Clinic at University Hospital, presenting with pain, nasal obstruction, and complaints of odynophagia and dysphagia. Physical examination showed painful, hyperemic and friable lesion in the right nasal cavity, associated with infiltrative lesion on the hard and soft palate, and uvula (Figure 1c). We observed ulcerated lesion on the left eyebrow and right eye with seropurulent secretion, a small ulcer on the lower eyelid, on the lobe of the right ear and a lesion in the malar region. The patient was admitted for diagnosis and treatment of disseminated skin lesions. A biopsy of the palate lesions revealed a non-specific erosive chronic inflammatory process. The patient was HIV negative and positive for Montenegro reaction. Treatment with amphotericin B was initiated at a dose of 150 mg/d up to a maximum dose of 2,410 mg. Lesions regressed after drug treatment and oral treatment was initiated during hospitalization. We removed dental foci without any intercurrence. One month later, the patient was discharged. However, in August 2013, in outpatient medical consultation, the lesions were observed in nasal mucosa and palate. He was followed up in the outpatient clinic and treatment with glucantime 20 mg/kg/day was prescribed for one month. The follow-up period was eight months, and the result was negative.

Case 3

Female, 31 years old, Caucasian, unemployed, from Salvador, State of Bahia, was diagnosed (Montenegro positive test) with American Tegumentary Leishmaniasis in October, 2011. The patient was treated with Glucantime, 20 mg/kg/day for 30 days. A lesion in her back region was partially healed. In 2012, two episodes of recurrence occurred and restarted treatment with Glucantime in January and May. In a third recurrence episode (August, 2012), due to the maintenance of the lesion, a lesion biopsy was performed and Leishmania braziliensis was diagnosed. Treatment with amphotericin B was initiated at a dose of 250 mg/d up to a maximum dose of 2,400 mg, resulting in wound healing. In 2013, the patient was admitted with submandibular lymphadenopathy and ulcerated lesions in the lower lip frenulum (Figure 1d), gingiva, nasal septum and in the back region. She was hospitalized for diagnosis and treatment of lesions with liposomal amphotericin B. Due to persistence of the lesions, HIV serology was performed. The patient was HIV positive and antiretroviral therapy was started (efavirenz 600mg, tenofovir 300mg, lamivudine 300mg, per day, one tablet containing the three drugs). Excisional biopsies of oral lesions were performed with unspecific result. Microbiological analysis for fungi was negative. Two months later, the patient was discharged and a maintenance dose of liposomal amphotericin B (150 mg/day) was prescribed.

Case 4

In 2017, an eight year-old Caucasian male from Salvador, Bahia, Brazil, presented with a hyperemic and pruritic lesion on the upper lip which had persisted for six months. Patient was treated with acyclovir cream, 5%, 5 times/day and cefadroxil (50 mg/kg/day) for seven days, with no response. He presented worsening of the lesion and Montenegro intradermal examination was performed (Figure 2a). The patient was positive for American Tegumentary Leishmaniasis. Treatment with glucantime (10 mg/day) for 20 days was initiated. After three days of treatment, the patient developed vomiting episodes, intermittent fever, diarrhea, hypoglycemia, dark urine, and began developing a reaction of cardiotoxicity and hepatoxicity. Treatment with liposomal amphotericin B was initiated (3 mg/kg/day for 5 days, followed by 3 mg/kg). One month later, patient was discharged with remission of the lesion (Figure 2b). Two months later, the patient was admitted at University Hospital with a new, erythematous and ulcerated lesion on the upper lip lesion, lymphadenopathy, and facial edema. Therapy with amoxicillin 250 mg (1g/day) and amphotericin B (100 mg/day) for 10 days was started. Patient is currently in psychological follow-up due to trauma caused by facial disfiguration and difficulty in returning to social life. Patient maintained outpatient follow-up and did not present with recurrence of the lesion.

Figure 2.

Hyperemic and pruritic lesion on the upper lip, reported at Case-4 (a); Aspect of the upper lip one month later, evidenced remission of lesion (b).

Case 5

In 2008, a male, 30 years old, Caucasian, unemployed, HIV – negative, with no other concomitant infections, presented with an isolated nodulation in the right leg and he was diagnosed with Tegumentary leishmaniasis. The patient was treated with Glucantime (10 mg/kg/day for 20 days), achieving complete healing of the lesions. In 2014 the patient presented a papule in the inferior eyelid of the right eye. Patient was PCR positive for Leishmania brasiliensis. Lesions progressively appeared in different body surfaces such as the chest, abdomen, back, feet, and mouth. Ulcerated oral lesions were present in the hard palate, as well as the left and right jugal mucosa (Figure 3a).

Figure 3.

Ulcerated oral lesions in hard palate reported at Case-5 (a). Leishmaniasis lesion in the left malar region reported at Case-6 (b).

Progression of disease was associate with fever, headache and weight loss. Treatment with glucantime (20 mg/day) for 30 days followed by treatment with amphotericin B at a cumulative dose of 1.5 to 2 g, 50 mg/day. Patient developed acute renal failure secondary to the use of amphotericin B. Treatment was replaced by the liposomal form at a dose of 100 mg/day and patient was discharge one month later with complete remission of lesions.

Case 6

Female, 59 years old, Caucasian, unemployed, with diabetes, hypertension, congestive heart failure, chronic renal disease and paraparesis secondary to Human T-cell leukemia virus type 1 (HTLV-1) infection. In June 2012, patient presented with a papule lesion in the left malar region with late ulceration and increasing in size (Figure 3b). After 15 days, another lesion developed in the right knee. Patient was positive for Montenegro intradermal test and diagnosed with mucocutaneous leishmaniasis and was admitted in the University Hospital in September 2012. Patient developed hyperkalemia and, after stabilization of renal function, treatment with liposomal amphotericin B (100 mg/day) was introduced. One day after, the patient developed another episode of renal dysfunction and therapy was discontinued. Five days later, therapy was reintroduced, alternating with dialysis. The culture examination of the malleolar lesion was performed, being positive for Proteus vulgaris and hemoculture was positive for Staphylococcus aureus. In October 2012, patient was transferred to intensive care unit and developed multiple organ failure, dying two weeks later.

Case 7

Male, 59 years old, mixed ethnicity, unemployed, previously healthy, reported the appearance of an erythematous-crusty lesions in the mental protuberance region, evolving in two months to other parts of the body such as frontal and occipital regions, nasal septum, ears, hands, and lower limbs. Oral cavity clinic-examination showed scattered ulcers on the face, lower labial mucosa, and on the left lip commissure, pseudomembrane on the marginal gingiva, and an exophytic nodule in the left labial mucosa (Figure 4). Patient was Montenegro intradermal test positive and was admitted at the University Hospital in December 2018. After admission, we observed enlarged lymph nodes of hard consistency in the left inguinal region, and an extensive melanocytic lesion in the left plantar region. The lesion was irregular, presenting an area of hyperkeratosis with a grey-bluish center. The patient was biopsied and the diagnostic hypothesis of melanoma was confirmed. We requested laboratory and imaging tests for melanoma staging. After seven days, we accessed the PCR laboratory test and initiated therapy with intravenous liposomal amphotericin B 50 mg at the dose of 200 mg/kg/day for 15 days (Figure 4). Diagnostic confirmation of melanoma resulted in the excision of the melanocytic lesion with left inguinal lymphadenectomy. Patient was referred to an oncology center. The patient has not yet returned for evaluation as they are receiving antineoplastic treatment outside our hospital.

Figure 4.

Ulcerated lesions in face, marginal gingiva, palate, and labial mucosa, before (a) and after treatment with liposomal amphotericin B (b) reported at Case-7.

Discussion

Five out of the seven cases were males from Brazil’s endemic regions. Four cases had associated comorbidities (SLE, HIV, HTLV infection and melanoma). A multicenter case series study¹ with seven patients presenting oral leishmaniasis reported higher frequency of oral lesions in males (86%), tongue (57%) with predominance of exophytic lesions (85%). In our case series, patients were predominantly males with ulcerated lesions in the lips.

The Montenegro reaction is a diagnosis test of high sensitivity, low cost and minimally invasive. Serological tests, such as immunoenzymatic assays and indirect immunofluorescence, show variation in their results depending on the applied technique and disease classification¹⁰. In our series of cases, late diagnosis was observed resulting in treatment delay and extension of hospitalization stay.

Facial involvement of leishmaniasis is a serious complication, since it can lead to disfiguration and be potentially fatal^11,12. In one case reported, the patient had severe psychological consequences due to facial deformity, reinforcing the importance of early diagnosis and appropriate therapy.

Mucosal leishmaniasis is generally associated with visceral leishmaniasis or immunocompromised individuals^13–16. In immunocompetent patients, primary and exclusive mucosal involvement in the head and neck region is uncommon; lesions affecting the buccal mucosa exclusively are even rarer^1,15–19. In our series of cases, four cases (57.1%) presented some level of immunological deficiency.

Leishmaniasis is difficult to treat, and may present with spontaneous reactivation²⁰ or be transmitted by a transplanted organ²¹. Control of cutaneous leishmaniasis depends on case management, early detection and appropriate treatment²². We observed cases of adverse drug reactions during treatment and protocol changes were necessary during the course of treatment. We also observed frequent recurrence of lesions, probably associated with immunossupression and therapeutic failure with inadequate treatment suspension or suboptimal doses.

Oral lesions of leishmaniasis are rare; however, oral mucosa may be one of the manifestations sites of the disease. In this context, the dental surgeon plays a fundamental role in the early diagnosis of oral lesions of leishmaniasis³. The great variability of clinical presentation of the lesions and frequent unspecific histopathology represent a challenge in regard to differential diagnoses. The dental surgeon can contribute to early diagnosis of mucosal lesions, since oral mucosa may be the primary site of the disease manifestation.

Although histopathological techniques describe the inflammatory infiltrate associated to leishmaniasis, they present low diagnostic specificity. The granulomatous aspect of lesions in later stages of cutaneous infection of leishmaniasis hampers histopathological analysis, since few parasites can be found in these lesions^1,7,23. In our reported cases, we had two unspecific biopsy results.

Differential diagnosis of mucosal lesions should include mucosal leishmaniasis. The variation in the clinical presentation of leishmaniasis and its ability to mimic different diseases represent a challenge for disease diagnosis. Due to the granulomatous ulcerated aspect of leishmaniasis lesions, squamous cell carcinoma and deep fungal infections, such as paracoccidioidomycosis and histoplasmosis, are differential diagnoses. In the reported cases, negative biopsies and cultures for these mycoses, and the absence of malignant neoplasia in histological sections, followed by the cure of lesions treated with amphotericin, in patients with confirmed skin leishmaniasis lesions by Montenegro reaction or PCR, confirmed that the all described lesions were oral manifestations of leishmaniasis.

There is no specific standardization for mucocutaneous leishmaniasis therapy^17,22. The cases we reported were submitted to different therapeutic plans, adjusted to each patient. In our case series, all patients received systemic treatment for mucocutaneous leishmaniasis, because of this disease well-known resistance. Alternative topical treatment includes use of ointment, cryotherapy, and intralesional injection with antimonials. Multiple and large lesions compromising the face are less suitable for local therapy. The treatment of mucosal leishmaniasis are still based on case reports⁹.

Cutaneous leishmaniasis is not life-threatening; however, its treatment may cause serious adverse effects and sometimes lead to death. Recently, safer local treatments have been included among acceptable therapies for New World leishmaniasis cases. The use of intralesional meglumine antimoniate (IL-MA) is recommended for patients with single skin lesions, <3 cm in diameter, in any region of the body, except in the head and periarticular sites; the volume of injected MA should not exceed 5 mL²⁴. Intralesional infiltration of pentavalent antimonial derivatives has emerged as potentially effective as intravenous therapy; however, there is a lack of robust safety data²⁵, obtained by controlled clinical trials to test drug efficacy and safety²⁶.

In our cases, all patients were treated with systemic medication. We presented a case with primary and exclusive lesion on the lip. Local treatment was not administered, and the patient is under follow-up.

Our findings present some limitation. First, the few cases reported are not a representative population sample, limiting any possible inference. Due to socioeconomic reasons, patients living far from Salvador are not accessible for a close follow-up and dental care. Diagnosis based on oral biopsies are very limited and the dental surgeon must be aware of the diverse clinical forms of leishmaniasis. Cases of orofacial mucosa leishmaniasis are rare, but we should be aware of them during oral examination. We agree that our report may contribute to a better dental evaluation and early diagnosis of cases of oral leishmaniasis.

Conclusions

The present study highlights the importance of a multidisciplinary approach in the diagnosis and treatment of orofacial leishmaniasis. Patients that travelled or live in endemic regions and presenting atypical lesions should be investigated for leishmaniasis. This could avoid delays in diagnosis and decrease the risk of the disease dissemination.

Data availability

Underlying data

All data underlying the results are available as part of the article and no additional source data are required.

Faculty Opinions recommended

References

1. Mignogna MD, Celentano A, Leuci S, et al.: Mucosal leishmaniasis with primary oral involvement: a case series and a review of the literature. Oral Dis. 2015; 21(1): e70–8. PubMed Abstract | Publisher Full Text
2. World Health Organization: Control of the leishmaniases. World Health Organ Tech Rep Ser. 2010; (949): xii–xiii, 1–186, back cover. PubMed Abstract
3. Pellicioli AC, Martins MA, Sant'ana Filho M, et al.: Leishmaniasis with oral mucosa involvement. Gerodontology. 2012; 29(2): e1168–71. PubMed Abstract | Publisher Full Text
4. Crovetto-Martínez R, Aguirre-Urizar JM, Orte-Aldea C, et al.: Mucocutaneous leishmaniasis must be included in the differential diagnosis of midline destructive disease: two case reports. Oral Surg Oral Med Oral Pathol Oral Radiol. Elsevier Inc.; 2015; 119(1): e20–6. PubMed Abstract | Publisher Full Text
5. Celentano A, Ruoppo E, Mansueto G, et al.: Primary oral leishmaniasis mimicking oral cancer: a case report. Br J Oral Maxillofac Surg. British Association of Oral and Maxillofacial Surgeons; 2015; 53(4): 396–8. PubMed Abstract | Publisher Full Text
6. Cruz AF, Resende RG, Albuquerque DR, et al.: Mucosal leishmaniasis in Brazilian patients: two case reports with similar clinical presentation and different approaches. Oral Surg Oral Med Oral Pathol Oral Radiol. Elsevier Ltd; 2016; 122(6): e199–203. PubMed Abstract | Publisher Full Text
7. Okumura Y, Yamauchi A, Nagano I, et al.: A case of mucocutaneous leishmaniasis diagnosed by serology. J Dermatol. 2014; 41(8): 739–42. PubMed Abstract | Publisher Full Text
8. Cobo F, Rodríguez-Granger J, Gómez-Camarasa C, et al.: Localized mucosal leishmaniasis caused by Leishmania infantum mimicking cancer in the rhinolaryngeal region. Int J Infect Dis. 2016; 50: 54–6. PubMed Abstract | Publisher Full Text
9. Blum J, Lockwood DNJ, Visser L, et al.: Local or systemic treatment for New World cutaneous leishmaniasis? Re-evaluating the evidence for the risk of mucosal leishmaniasis. Int Health. Royal Society of Tropical Medicine and Hygiene; 2012; 4(3): 153–63. PubMed Abstract | Publisher Full Text
10. Gomes CM, Paula NA, Morais OO, et al.: Complementary exams in the diagnosis of American tegumentary leishmaniasis. An Bras Dermatol. 2014; 89(5): 701–9. PubMed Abstract | Publisher Full Text | Free Full Text
11. Almeida TF, da Silveira EM, Dos Santos CR, et al.: Exclusive Primary Lesion of Oral Leishmaniasis with Immunohistochemical Diagnosis. Head Neck Pathol. 2016; 10(4): 533–7. PubMed Abstract | Publisher Full Text | Free Full Text
12. Passi D, Sharma S, Dutta S, et al.: Localised leishmaniasis of oral mucosa: report of an unusual clinicopathological entity. Case Rep Dent. Hindawi Publishing Corporation; 2014; 2014: 753149. PubMed Abstract | Publisher Full Text | Free Full Text
13. Cobo F, Aliaga L, Talavera P, et al.: The histological spectrum of non-granulomatous localized mucosal leishmaniasis caused by Leishmania infantum. Ann Trop Med Parasitol. 2007; 101(8): 689–94. PubMed Abstract | Publisher Full Text
14. Ramos A, Múñez E, García-Domínguez J, et al.: Mucosal leishmaniasis mimicking squamous cell carcinoma in a liver transplant recipient. Transpl Infect Dis. 2015; 17(3): 488–92. PubMed Abstract | Publisher Full Text
15. Rathnayake D, Ranawake RR, Sirimanna G, et al.: Co-infection of mucosal leishmaniasis and extra pulmonary tuberculosis in a patient with inherent immune deficiency. Int J Dermatol. 2010; 49(5): 549–51. PubMed Abstract | Publisher Full Text
16. Torrico F, Parrado R, Castro R, et al.: Co-Infection of Leishmania (Viannia) braziliensis and HIV: report of a case of mucosal leishmaniasis in Cochabamba, Bolivia. Am J Trop Med Hyg. 2009; 81(4): 555–8. PubMed Abstract | Publisher Full Text
17. Lee GL, Woods KL, Clark L, et al.: Short communication: mucocutaneous leishmaniasis in HIV-related immune reconstitution syndrome. AIDS Res Hum Retroviruses. 2015; 31(9): 889–92. PubMed Abstract | Publisher Full Text
18. Gois L, Badaró R, Schooley R, et al.: Immune response to Leishmania antigens in an AIDS patient with mucocutaneous leishmaniasis as a manifestation of immune reconstitution inflammatory syndrome (IRIS): a case report. BMC Infect Dis. 2015; 15(1): 38. PubMed Abstract | Publisher Full Text | Free Full Text
19. Madeddu G, Fiori ML, Ena P, et al.: Mucocutaneous leishmaniasis as presentation of HIV infection in Sardinia, insular Italy. Parasitol Int. Elsevier Ireland Ltd; 2014; 63(1): 35–6. PubMed Abstract | Publisher Full Text
20. Nadler C, Enk CD, Leon GT, et al.: Diagnosis and management of oral leishmaniasis--case series and literature review. J Oral Maxillofac Surg. American Association of Oral and Maxillofacial Surgeons; 2014; 72(5): 927–34. PubMed Abstract | Publisher Full Text
21. Baglieri F, Scuderi G: A case of mucosal leishmaniasis of the tongue in a kidney transplant recipient. Int J Dermatol. 2012; 51(5): 597–600. PubMed Abstract | Publisher Full Text
22. González U, Pinart M, Rengifo-Pardo M, et al.: Interventions for American cutaneous and mucocutaneous leishmaniasis. Cochrane Database Syst Rev. 2009; (2): CD004834. PubMed Abstract | Publisher Full Text
23. Palmeiro MR, Rosalino CM, Quintella LP, et al.: Gingival leishmaniasis in an HIV-negative patient. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007; 104(6): e12–6. PubMed Abstract | Publisher Full Text
24. de Oliveira Duque MC, Quintão Silva JJ, Soares PAO, et al.: Comparison between systemic and intralesional meglumine antimoniate therapy in a primary health care unit. Acta Trop. 2019; 193: 176–182. PubMed Abstract | Publisher Full Text
25. Fernandes HJ, da Silva RE, Ramalho DB, et al.: Safety profile of meglumine antimoniate intralesional infiltration for cutaneous leishmaniasis. Expert Rev Anti Infect Ther. 2020; 18(4): 381–387. PubMed Abstract | Publisher Full Text
26. Arboleda M, Barrantes S, Úsuga LY, et al.: Successful treatment of cutaneous leishmaniasis with intralesional meglumine antimoniate: A case series. Rev Soc Bras Med Trop. 2019; 52: e20180211. PubMed Abstract | Publisher Full Text

Comments on this article Comments (0)

Version 4

VERSION 4 PUBLISHED 29 May 2019

Author details Author details

¹ Professor Edgard Santos Hospital, Federal University of Bahia, Salvador, BA, 40110060, Brazil

Gleicy Gabriela Vitória Spinola Carneiro Falcão
Roles: Investigation, Writing – Original Draft Preparation

Liliane Lins-Kusterer
Roles: Conceptualization, Writing – Review & Editing

Patricia Miranda Leite-Ribeiro
Roles: Investigation, Writing – Review & Editing

Viviane Almeida Sarmento
Roles: Conceptualization, Supervision, Writing – Review & Editing

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

Article Versions (4)

version 4

Revised

Published: 24 Sep 2020, 8:756

https://doi.org/10.12688/f1000research.19056.4

version 3

Revised

Published: 19 Jun 2020, 8:756

https://doi.org/10.12688/f1000research.19056.3

version 2

Revised

Published: 16 Apr 2020, 8:756

https://doi.org/10.12688/f1000research.19056.2

version 1

Published: 29 May 2019, 8:756

https://doi.org/10.12688/f1000research.19056.1

© 2020 Falcão GGVSC et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download

Export To

metrics

	Views	Downloads
F1000Research	-	-
PubMed Central Data from PMC are received and updated monthly.	-	-

Citations

SEE MORE DETAILS

CITE

how to cite this article

Falcão GGVSC, Lins-Kusterer L, Leite-Ribeiro PM and Sarmento VA. Orofacial manifestations of mucocutaneous leishmaniasis: a case series from Brazil [version 2; peer review: 1 approved, 1 approved with reservations]. F1000Research 2020, 8:756 (https://doi.org/10.12688/f1000research.19056.2)

NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.

track

receive updates on this article

Track an article to receive email alerts on any updates to this article.

Open Peer Review

Version 2

VERSION 2

PUBLISHED 16 Apr 2020

Revised

Views

Reviewer Report 11 May 2020

Elismauro Francisco Mendonça, Department of Oral Medicine (Oral Pathology), Dental School, Federal University of Goiás, Goiânia, Brazil

Approved

https://doi.org/10.5256/f1000research.25383.r62518

This paper is very interesting. It is well written and with scientific evidences. This lesion has clinical diagnosis very complex and the criteria used by the authors was well discussed in the paper.

Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Yes, the authors have showed for each case presented the investigation methods including diagnostic tests, as well as, the treatment. Although in some cases there was recurrence the lesion after protocol treatment, we believe that economic condition of the patients might contribute to unsuccessful treatment. Other point is the access to public health system in the country nor always favorable. In addition, the authors have discussed this aspect and limitations.

Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

The discussion section was well presented , however would be interesting the authors to include which is the best scientific evidence for treatment in the actual moment? For example, glucantinme or anphotericin ? Or other?

Is the case presented with sufficient detail to be useful for other practitioners?

Yes, but in my opinion in the discussion section the authors should emphasize the high index of recurrence associated to treatment protocol used and comorbidities. Maybe the protocol treatment was not followed by the patient as prescribed by medical team.

Is the background of the case’s history and progression described in sufficient detail?

Yes, the cases are well presented and clinical history can be easily followed by the reader.
----------------------------------------------------------------------------------------------------------------------------------------------------------

Is the background of the cases’ history and progression described in sufficient detail?

Yes
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Yes
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Yes
Is the conclusion balanced and justified on the basis of the findings?

Yes

Competing Interests: No competing interests were disclosed.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

CITE

Report a concern

Respond or Comment

Views

Reviewer Report 21 Apr 2020

Braulio Valencia, Viral Immunology Systems Program (VISP), Kirby Institute, Universidad Peruana Cayetano Heredia, Kensington, Australia

Approved with Reservations

https://doi.org/10.5256/f1000research.25383.r62403

The following observations have not been addressed:

Case 6: This is purely a DisL case. Due to the lack of oral involvement, this case is eminently of the dermatology or infectious diseases fields.

The following observations have not been addressed:

Case 6: This is purely a DisL case. Due to the lack of oral involvement, this case is eminently of the dermatology or infectious diseases fields.
Case 7: as in case 6, no substantial evidence was provided to assume oral involvement. Authors described "we accessed the PCR laboratory test", but it's not clear where was this sample obtained. Partial improvement of the oral lesion after AMB is not conclusive to assume the parasitic etiology.
Paragraph 4: there is no reasonable evidence suggesting MCL is generally associated with VL or immunosuppression. All references supporting this statement (11-19) are case reports informing unusual clinical presentations. It's highly recommended to authors review https://doi.org/10.1016/B978-0-323-55512-8.00104-6 for a better understanding of the pathobiology and risk factors of MCL.
Paragraph 8 and 9: authors must review the therapeutic section of https://doi.org/10.1016/B978-0-323-55512-8.00104-6 to understand how differently pure mucosal lesions and cutaneous lesions are treated. In the context of oral leishmaniasis, the suggestion of topical therapy for mucosal lesions is unacceptable.

These are significant imprecisions which, if not addressed, are going to generate a deficient review.

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Infectious and Tropical Diseases, Neglected Tropical Diseases, New-World Leishmaniases.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

CITE

Report a concern

Author Response 21 May 2020

Viviane Sarmento, Professor Edgard Santos Hospital, Federal University of Bahia, Salvador, 40110060, Brazil

21 May 2020

Author Response

Dear reviewer,

Thank you for your considerations about the paper entitled “Orofacial manifestations of mucocutaneous leishmaniasis: a case series from Brazil”. Each point will be discussed below:

Case 6: This is purely ... Continue reading Dear reviewer,

Thank you for your considerations about the paper entitled “Orofacial manifestations of mucocutaneous leishmaniasis: a case series from Brazil”. Each point will be discussed below:

Case 6: This is purely a DisL case. Due to the lack of oral involvement, this case is eminently of the dermatology or infectious diseases fields.

We appreciate your considerations. However, we would like to highlight that we have proposed to report, not only cases with oral involvement, but also mucocutaneous leishmaniasis on the face, because the dentist also evaluates this area. Therefore, case 6 fits the pre-established criteria.

2. Case 7: as in case 6, no substantial evidence was provided to assume oral involvement. Authors described "we accessed the PCR laboratory test", but it's not clear where was this sample obtained. Partial improvement of the oral lesion after AMB is not conclusive to assume the parasitic etiology.

Thank you for your comments. Case 7 was first diagnosed with mucocutaneous leishmaniasis by the Monte Negro test, performed in the patient's city of origin. The patient was referred to the hospital for treatment. However, the treatment with amphotericin was only initiated after PCR confirmation.

3. Paragraph 4: there is no reasonable evidence suggesting MCL is generally associated with VL or immunosuppression. All references supporting this statement (11-19) are case reports informing unusual clinical presentations. It's highly recommended to authors review https://doi.org/10.1016/B978-0-323-55512-8.00104-6 for a better understanding of the pathobiology and risk factors of MCL.

There are reports of cases of leishmaniasis with the involvement of the oral mucosa in patients with immunosuppression (HIV, transplant patients), but this does not associate the disease with such risk factors. We decided to change in the text to the following sentence: Leishmaniasis should be considered in immunocompromised patients.

4. Paragraph 8 and 9: authors must review the therapeutic section of https://doi.org/10.1016/B978-0-323-55512-8.00104-6 to understand how differently pure mucosal lesions and cutaneous lesions are treated. In the context of oral leishmaniasis, the suggestion of topical therapy for mucosal lesions is unacceptable.

Thanks for your comments. However, according to the cited reference concerning local therapy, the "experience with local therapy for New World CL is limited, as local therapy was long considered unsuitable, especially in those patients infected with L. (V.) Braziliensis or L. (V. ) panamensis because of the potential risk of ML and the expectation that systemic treatment could prevent metastasis and mucosal involvement. However, systemic treatment does not guarantee the prevention of later ML. World CL."
Dear reviewer,

Thank you for your considerations about the paper entitled “Orofacial manifestations of mucocutaneous leishmaniasis: a case series from Brazil”. Each point will be discussed below:

Case 6: This is purely a DisL case. Due to the lack of oral involvement, this case is eminently of the dermatology or infectious diseases fields.

We appreciate your considerations. However, we would like to highlight that we have proposed to report, not only cases with oral involvement, but also mucocutaneous leishmaniasis on the face, because the dentist also evaluates this area. Therefore, case 6 fits the pre-established criteria.

2. Case 7: as in case 6, no substantial evidence was provided to assume oral involvement. Authors described "we accessed the PCR laboratory test", but it's not clear where was this sample obtained. Partial improvement of the oral lesion after AMB is not conclusive to assume the parasitic etiology.

Thank you for your comments. Case 7 was first diagnosed with mucocutaneous leishmaniasis by the Monte Negro test, performed in the patient's city of origin. The patient was referred to the hospital for treatment. However, the treatment with amphotericin was only initiated after PCR confirmation.

3. Paragraph 4: there is no reasonable evidence suggesting MCL is generally associated with VL or immunosuppression. All references supporting this statement (11-19) are case reports informing unusual clinical presentations. It's highly recommended to authors review https://doi.org/10.1016/B978-0-323-55512-8.00104-6 for a better understanding of the pathobiology and risk factors of MCL.

There are reports of cases of leishmaniasis with the involvement of the oral mucosa in patients with immunosuppression (HIV, transplant patients), but this does not associate the disease with such risk factors. We decided to change in the text to the following sentence: Leishmaniasis should be considered in immunocompromised patients.

4. Paragraph 8 and 9: authors must review the therapeutic section of https://doi.org/10.1016/B978-0-323-55512-8.00104-6 to understand how differently pure mucosal lesions and cutaneous lesions are treated. In the context of oral leishmaniasis, the suggestion of topical therapy for mucosal lesions is unacceptable.

Thanks for your comments. However, according to the cited reference concerning local therapy, the "experience with local therapy for New World CL is limited, as local therapy was long considered unsuitable, especially in those patients infected with L. (V.) Braziliensis or L. (V. ) panamensis because of the potential risk of ML and the expectation that systemic treatment could prevent metastasis and mucosal involvement. However, systemic treatment does not guarantee the prevention of later ML. World CL."
Competing Interests: No competing interests were disclosed. Close
Report a concern
Respond or Comment

COMMENTS ON THIS REPORT

Author Response 21 May 2020

Viviane Sarmento, Professor Edgard Santos Hospital, Federal University of Bahia, Salvador, 40110060, Brazil

21 May 2020

Author Response

Dear reviewer,

Thank you for your considerations about the paper entitled “Orofacial manifestations of mucocutaneous leishmaniasis: a case series from Brazil”. Each point will be discussed below:

Case 6: This is purely ... Continue reading Dear reviewer,

Thank you for your considerations about the paper entitled “Orofacial manifestations of mucocutaneous leishmaniasis: a case series from Brazil”. Each point will be discussed below:

Case 6: This is purely a DisL case. Due to the lack of oral involvement, this case is eminently of the dermatology or infectious diseases fields.

We appreciate your considerations. However, we would like to highlight that we have proposed to report, not only cases with oral involvement, but also mucocutaneous leishmaniasis on the face, because the dentist also evaluates this area. Therefore, case 6 fits the pre-established criteria.

2. Case 7: as in case 6, no substantial evidence was provided to assume oral involvement. Authors described "we accessed the PCR laboratory test", but it's not clear where was this sample obtained. Partial improvement of the oral lesion after AMB is not conclusive to assume the parasitic etiology.

Thank you for your comments. Case 7 was first diagnosed with mucocutaneous leishmaniasis by the Monte Negro test, performed in the patient's city of origin. The patient was referred to the hospital for treatment. However, the treatment with amphotericin was only initiated after PCR confirmation.

3. Paragraph 4: there is no reasonable evidence suggesting MCL is generally associated with VL or immunosuppression. All references supporting this statement (11-19) are case reports informing unusual clinical presentations. It's highly recommended to authors review https://doi.org/10.1016/B978-0-323-55512-8.00104-6 for a better understanding of the pathobiology and risk factors of MCL.

There are reports of cases of leishmaniasis with the involvement of the oral mucosa in patients with immunosuppression (HIV, transplant patients), but this does not associate the disease with such risk factors. We decided to change in the text to the following sentence: Leishmaniasis should be considered in immunocompromised patients.

4. Paragraph 8 and 9: authors must review the therapeutic section of https://doi.org/10.1016/B978-0-323-55512-8.00104-6 to understand how differently pure mucosal lesions and cutaneous lesions are treated. In the context of oral leishmaniasis, the suggestion of topical therapy for mucosal lesions is unacceptable.

Thanks for your comments. However, according to the cited reference concerning local therapy, the "experience with local therapy for New World CL is limited, as local therapy was long considered unsuitable, especially in those patients infected with L. (V.) Braziliensis or L. (V. ) panamensis because of the potential risk of ML and the expectation that systemic treatment could prevent metastasis and mucosal involvement. However, systemic treatment does not guarantee the prevention of later ML. World CL."
Dear reviewer,

Thank you for your considerations about the paper entitled “Orofacial manifestations of mucocutaneous leishmaniasis: a case series from Brazil”. Each point will be discussed below:

Case 6: This is purely a DisL case. Due to the lack of oral involvement, this case is eminently of the dermatology or infectious diseases fields.

We appreciate your considerations. However, we would like to highlight that we have proposed to report, not only cases with oral involvement, but also mucocutaneous leishmaniasis on the face, because the dentist also evaluates this area. Therefore, case 6 fits the pre-established criteria.

2. Case 7: as in case 6, no substantial evidence was provided to assume oral involvement. Authors described "we accessed the PCR laboratory test", but it's not clear where was this sample obtained. Partial improvement of the oral lesion after AMB is not conclusive to assume the parasitic etiology.

Thank you for your comments. Case 7 was first diagnosed with mucocutaneous leishmaniasis by the Monte Negro test, performed in the patient's city of origin. The patient was referred to the hospital for treatment. However, the treatment with amphotericin was only initiated after PCR confirmation.

3. Paragraph 4: there is no reasonable evidence suggesting MCL is generally associated with VL or immunosuppression. All references supporting this statement (11-19) are case reports informing unusual clinical presentations. It's highly recommended to authors review https://doi.org/10.1016/B978-0-323-55512-8.00104-6 for a better understanding of the pathobiology and risk factors of MCL.

There are reports of cases of leishmaniasis with the involvement of the oral mucosa in patients with immunosuppression (HIV, transplant patients), but this does not associate the disease with such risk factors. We decided to change in the text to the following sentence: Leishmaniasis should be considered in immunocompromised patients.

4. Paragraph 8 and 9: authors must review the therapeutic section of https://doi.org/10.1016/B978-0-323-55512-8.00104-6 to understand how differently pure mucosal lesions and cutaneous lesions are treated. In the context of oral leishmaniasis, the suggestion of topical therapy for mucosal lesions is unacceptable.

Thanks for your comments. However, according to the cited reference concerning local therapy, the "experience with local therapy for New World CL is limited, as local therapy was long considered unsuitable, especially in those patients infected with L. (V.) Braziliensis or L. (V. ) panamensis because of the potential risk of ML and the expectation that systemic treatment could prevent metastasis and mucosal involvement. However, systemic treatment does not guarantee the prevention of later ML. World CL."
Competing Interests: No competing interests were disclosed. Close
Report a concern

Version 1

VERSION 1

PUBLISHED 29 May 2019

Views

Reviewer Report 04 Nov 2019

Braulio Valencia, Viral Immunology Systems Program (VISP), Kirby Institute, Universidad Peruana Cayetano Heredia, Kensington, Australia

Not Approved

https://doi.org/10.5256/f1000research.20884.r55589

The scope of this article is to provide essential clues about orofacial manifestations of mucocutaneous leishmaniasis. Considering the target readers are Dental Surgeons, this manuscript has several imprecision's and inaccurate messages which need to be corrected.

Abstract section: ... Continue reading

The affirmation that "oral mucosa may be the primary site of the disease manifestation" is contradictory with the discussion and findings of this report as well as the existent and well-characterised clinical description of MCL. Almost all cases (except case 4) were manifested as disseminated Leishmaniasis with a significant and predominant cutaneous involvement. In the discussion section, paragraph four, line 5, authors state that primary and exclusive oral mucosa involvement is exceptionally uncommon. Then, what is described in the abstract is contradictory.
Regarding that "All had mucocutaneous leishmaniasis with oropharyngeal involvement" is also incorrect. Due to the lack of detail in cases 5-7, it is not possible to accept these cases are definitively MCL. Case 6 is not a case of MCL; then, it needs to be removed from this article.

Introduction section:

Paragraph 2, line 1-2: It's not clear if authors suggest that MCL is particularly frequent in immunosuppressed individuals. This affirmation is highly dependent on the prevalence of immunosuppressive comorbidities (as HIV). Considering that immunosuppressive conditions are not highly prevalent in endemic areas (except some African or Asian regions), this affirmation is inaccurate. Mucosal involvement in new-world Leishmaniases ranges from 5-20%¹. Then, in any case, this affirmation is not correct or requires clarification.
Paragraph 2, line 5-6: development of primary lesions in oral mucosa is very infrequent and mainly described in old-world Leishmaniasis² OR in individuals with immunosuppressive conditions (4/7 cases in this report). For this reason, authors must consider changing the scope (title as well?) of this review from orofacial manifestations of MCL to atypical manifestations of leishmaniasis among immunosuppressed individuals.

Case reports:

Case 1: more than MCL, this is a case of disseminated leishmaniasis (DisL) in an immunosuppressed individual. Here the predominant mucosal involvement appears to be nasal (no details are provided regarding the degree of nasal involvement), and the oral involvement is confined to the upper lip involvement. This is unusual even in immunosuppressed individuals, considering that lips, gums, tongue, and hard palate are extremely infrequent in new-world MCL³.
Case 2: again, this is a case of DisL in an immunocompetent individual. Here the mucosal involvement is more typical, but an HIV seronegative status is not enough to classify the patient as immunocompetent. A better characterisation of this individual is required.
Case 3: again, another case of DisL in an immunocompromised patient. It's recommended to improve the quality of picture 1d. As mentioned before gums are unusual in new-world MCL. MCL is not commonly associated with lymphadenopathy. Both findings, and in the absence of parasitologic or histologic characterisation of the oral lesion makes it essential to consider other infectious diseases, importantly in an HIV-seropositive individual.
Case 4: this case is MCL, but the pathophysiology is different from the prior cases. Here, more than a lymphatic/hematologic dissemination, what generated the MCL was a direct inoculation on the lip or a skin inoculation close to a mucosal structure. This case is clearly, utterly different from the rest and hard to classify as an unusual manifestation or among immunosuppressed individuals.
Case 5: again, another DisL in an apparently immunocompetent patient. No details were provided here regarding the HIV serologic status or other potential sources of immunosuppression.
Case 6: again, another DisL in an immunosuppressed individual. In this case, there is not any oral or mucosal involvement (only cutaneous lesions are described). Then, this case must be removed from the report.
Case 7: there is a lack of evidence to catalogue this case as MCL. Besides the facial cutaneous lesions (only localised cutaneous leishmaniasis?), lesions described in the oral mucosa are unusually located, and an alternative explanation must be considered (metastatic melanoma?). It's not clear where the sample for PCR was obtained. With this unclear clinical and parasitological description, it's inaccurate to define the case as MCL.

Discussion:

Paragraph 3, lines 1-2: MCL is potentially fatal, mainly when larynx or trachea are affected. From that scenario, it's incorrect to describe them as a facial involvement.
Paragraph 4, lines 1-2: as suggested in the first observation of the introduction section, authors are suggesting MCL is generally associated with VL or immunosuppression. That is probably acceptable in the context of Sudanese MCL; however, this is not the epidemiological context of the study. Regarding immunosuppression, as discussed in the same observation, due to the lack of coexistence between Leishmaniasis and immunosuppressive conditions, there is not any evidence supporting this affirmation. The references used to support this statement are case reports which were not designed to measure the prevalence of MCL among immunosuppressed individuals.
Paragraph 5, lines 6-7: the high rate of recurrences observed in these cases are not necessarily related to therapeutic issues. Immunosuppression is probably the primary determinant of therapeutic failure.
Paragraph 6, lines 6-8: again, this affirmation is contradictory with the findings of this report. Only one case was purely a "primary" MCL, in the rest, the predominant manifestation was the development of disseminated cutaneous lesions.
Paragraph 8, lines 5-6: the reason why systemic therapy was administered in all these cases is that systemic treatment is the only standard therapeutic regimen for MCL (not due to resistance issues). For a better understanding of current therapeutic recommendations, authors must review citation four⁴ and update reference 9.
Paragraph 9: no local therapy is currently recommended for MCL. This information must be improved or removed.

Conclusions:

Paragraph 2: what other infections must be considered as a differential diagnosis among oral lesions?

Is the background of the cases’ history and progression described in sufficient detail?

Partly
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Partly
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Partly
Is the conclusion balanced and justified on the basis of the findings?

Partly

References

1. Parrado R, Rojas E, Reithinger R, Delgado R, et al.: Leishmaniases in Bolivia: Comprehensive Review and Current Status. The American Journal of Tropical Medicine and Hygiene. 2009; 80 (5): 704-711 Publisher Full Text
2. El-Hassan A, Zijlstra E: 2. Mucosal leishmaniasis. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2001; 95: S19-S26 Publisher Full Text
3. Aronson N, Herwaldt BL, Libman M, Pearson R, et al.: Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH).Am J Trop Med Hyg. 2017; 96 (1): 24-45 PubMed Abstract | Publisher Full Text
4. Magill A: Leishmaniasis. 2013. 739-760 Publisher Full Text

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Infectious and Tropical Diseases, Neglected Tropical Diseases, New-World Leishmaniases.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

CITE

Report a concern

Respond or Comment

Comments on this article Comments (0)

Version 4

VERSION 4 PUBLISHED 29 May 2019

Open Peer Review

Reviewer Status

Reviewer Reports

	Invited Reviewers
	1	2
Version 4 (revision) 24 Sep 20	read
Version 3 (revision) 19 Jun 20	read
Version 2 (revision) 16 Apr 20	read	read
Version 1 29 May 19	read

Braulio Valencia, Universidad Peruana Cayetano Heredia, Kensington, Australia
Elismauro Francisco Mendonça, Federal University of Goiás, Goiânia, Brazil

Comments on this article

All Comments(0)

Add a comment

Browse by related subjects

Back to all reports

Reviewer Report

4 Views

30 Sep 2020 | for Version 4

Braulio Valencia, Viral Immunology Systems Program (VISP), Kirby Institute, Universidad Peruana Cayetano Heredia, Kensington, Australia

4 Views Cite this report Responses(0)

Approved

Nothing to comment.

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Infectious and Tropical Diseases, Neglected Tropical Diseases, New-World Leishmaniases.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Respond to this report

Responses (0)

Back to all reports

Reviewer Report

11 Views

22 Jun 2020 | for Version 3

Braulio Valencia, Viral Immunology Systems Program (VISP), Kirby Institute, Universidad Peruana Cayetano Heredia, Kensington, Australia

11 Views Cite this report Responses(1)

Approved With Reservations

Observation case 6: it's up to the editors consider if this case is suitable to be incorporated or not in the field of dentistry or oral health. In the lack of oral involvement, there is no rationale to include this case.

Observation case 7: if a confirmatory PCR was performed, authors must clearly state this PCR was based on a sampling obtained from the oral lesion. Due to this is a DisL case, PCR sample could be obtained from any of the more accessible samples.

Observation paragraph 4: the sentence "Leishmaniasis should be considered in immunocompromised patients" is unclear (it is assuming any Leishmaniasis, even localised cutaneous Leishmaniasis should be ....). "Unusual manifestations as DisL or purely oral Leishmaniasis should be considered in immunocompromised patients" is probably more accurate and supported by their findings.

Observation regarding therapy: again, references 17 and 21 are case reports. The authors must familiarise with evidence-based recommendations as the one provided in the prior review. Local treatment is exclusively recommended to localised cutaneous leishmaniasis. It's a wrong and dangerous recommendation to suggest local therapies are suitable for the treatment of mucosal leishmaniasis.

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Infectious and Tropical Diseases, Neglected Tropical Diseases, New-World Leishmaniases.

Respond to this report

Responses (1)

Author Response

02 Sep 2020

Viviane Sarmento, Professor Edgard Santos Hospital, Federal University of Bahia, Salvador, 40110060, Brazil

Dear Reviewer,

We appreciate your comments and made some changes to the manuscript. In case 7, the PCR analysis was performed in a laboratory outside the hospital. Unfortunately, it was not possible to identify exactly where the sample was collected for PCR analysis. We added this information.

In relation to paragraph 4, we have changed the phrase “Leishmaniasis should be considered in immunocompromised patients” by the phrase “Unusual manifestations as DisL or purely oral leishmaniasis should be considered in immunocompromised patients”.

Regarding therapeutics, we chose to exclude the references and the paragraph from the discussion about the controversial findings in the literature regarding the local treatment of leishmaniasis.

Thank you very much.
The authors

View more View less

Competing Interests

No competing interests were disclosed.

Back to all reports

Reviewer Report

5 Views

11 May 2020 | for Version 2

Elismauro Francisco Mendonça, Department of Oral Medicine (Oral Pathology), Dental School, Federal University of Goiás, Goiânia, Brazil

5 Views Cite this report Responses(0)

Approved

Is the background of the cases’ history and progression described in sufficient detail?

Yes
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Yes
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Yes
Is the conclusion balanced and justified on the basis of the findings?

Yes

Competing Interests

No competing interests were disclosed.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Respond to this report

Responses (0)

Back to all reports

Reviewer Report

14 Views

21 Apr 2020 | for Version 2

Braulio Valencia, Viral Immunology Systems Program (VISP), Kirby Institute, Universidad Peruana Cayetano Heredia, Kensington, Australia

14 Views Cite this report Responses(1)

Approved With Reservations

The following observations have not been addressed:

Case 6: This is purely a DisL case. Due to the lack of oral involvement, this case is eminently of the dermatology or infectious diseases fields.
Case 7: as in case 6, no substantial evidence was provided to assume oral involvement. Authors described "we accessed the PCR laboratory test", but it's not clear where was this sample obtained. Partial improvement of the oral lesion after AMB is not conclusive to assume the parasitic etiology.
Paragraph 4: there is no reasonable evidence suggesting MCL is generally associated with VL or immunosuppression. All references supporting this statement (11-19) are case reports informing unusual clinical presentations. It's highly recommended to authors review https://doi.org/10.1016/B978-0-323-55512-8.00104-6 for a better understanding of the pathobiology and risk factors of MCL.
Paragraph 8 and 9: authors must review the therapeutic section of https://doi.org/10.1016/B978-0-323-55512-8.00104-6 to understand how differently pure mucosal lesions and cutaneous lesions are treated. In the context of oral leishmaniasis, the suggestion of topical therapy for mucosal lesions is unacceptable.

These are significant imprecisions which, if not addressed, are going to generate a deficient review.

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Infectious and Tropical Diseases, Neglected Tropical Diseases, New-World Leishmaniases.

Respond to this report

Responses (1)

Author Response

21 May 2020

Viviane Sarmento, Professor Edgard Santos Hospital, Federal University of Bahia, Salvador, 40110060, Brazil

Dear reviewer,

Thank you for your considerations about the paper entitled “Orofacial manifestations of mucocutaneous leishmaniasis: a case series from Brazil”. Each point will be discussed below:

Case 6: This is purely a DisL case. Due to the lack of oral involvement, this case is eminently of the dermatology or infectious diseases fields.

We appreciate your considerations. However, we would like to highlight that we have proposed to report, not only cases with oral involvement, but also mucocutaneous leishmaniasis on the face, because the dentist also evaluates this area. Therefore, case 6 fits the pre-established criteria.

2. Case 7: as in case 6, no substantial evidence was provided to assume oral involvement. Authors described "we accessed the PCR laboratory test", but it's not clear where was this sample obtained. Partial improvement of the oral lesion after AMB is not conclusive to assume the parasitic etiology.

Thank you for your comments. Case 7 was first diagnosed with mucocutaneous leishmaniasis by the Monte Negro test, performed in the patient's city of origin. The patient was referred to the hospital for treatment. However, the treatment with amphotericin was only initiated after PCR confirmation.

3. Paragraph 4: there is no reasonable evidence suggesting MCL is generally associated with VL or immunosuppression. All references supporting this statement (11-19) are case reports informing unusual clinical presentations. It's highly recommended to authors review https://doi.org/10.1016/B978-0-323-55512-8.00104-6 for a better understanding of the pathobiology and risk factors of MCL.

There are reports of cases of leishmaniasis with the involvement of the oral mucosa in patients with immunosuppression (HIV, transplant patients), but this does not associate the disease with such risk factors. We decided to change in the text to the following sentence: Leishmaniasis should be considered in immunocompromised patients.

4. Paragraph 8 and 9: authors must review the therapeutic section of https://doi.org/10.1016/B978-0-323-55512-8.00104-6 to understand how differently pure mucosal lesions and cutaneous lesions are treated. In the context of oral leishmaniasis, the suggestion of topical therapy for mucosal lesions is unacceptable.

Thanks for your comments. However, according to the cited reference concerning local therapy, the "experience with local therapy for New World CL is limited, as local therapy was long considered unsuitable, especially in those patients infected with L. (V.) Braziliensis or L. (V. ) panamensis because of the potential risk of ML and the expectation that systemic treatment could prevent metastasis and mucosal involvement. However, systemic treatment does not guarantee the prevention of later ML. World CL."

View more View less

Competing Interests

No competing interests were disclosed.

Back to all reports

Reviewer Report

12 Views

04 Nov 2019 | for Version 1

Braulio Valencia, Viral Immunology Systems Program (VISP), Kirby Institute, Universidad Peruana Cayetano Heredia, Kensington, Australia

12 Views Cite this report Responses(0)

Not Approved

The affirmation that "oral mucosa may be the primary site of the disease manifestation" is contradictory with the discussion and findings of this report as well as the existent and well-characterised clinical description of MCL. Almost all cases (except case 4) were manifested as disseminated Leishmaniasis with a significant and predominant cutaneous involvement. In the discussion section, paragraph four, line 5, authors state that primary and exclusive oral mucosa involvement is exceptionally uncommon. Then, what is described in the abstract is contradictory.
Regarding that "All had mucocutaneous leishmaniasis with oropharyngeal involvement" is also incorrect. Due to the lack of detail in cases 5-7, it is not possible to accept these cases are definitively MCL. Case 6 is not a case of MCL; then, it needs to be removed from this article.

Introduction section:

Paragraph 2, line 1-2: It's not clear if authors suggest that MCL is particularly frequent in immunosuppressed individuals. This affirmation is highly dependent on the prevalence of immunosuppressive comorbidities (as HIV). Considering that immunosuppressive conditions are not highly prevalent in endemic areas (except some African or Asian regions), this affirmation is inaccurate. Mucosal involvement in new-world Leishmaniases ranges from 5-20%¹. Then, in any case, this affirmation is not correct or requires clarification.
Paragraph 2, line 5-6: development of primary lesions in oral mucosa is very infrequent and mainly described in old-world Leishmaniasis² OR in individuals with immunosuppressive conditions (4/7 cases in this report). For this reason, authors must consider changing the scope (title as well?) of this review from orofacial manifestations of MCL to atypical manifestations of leishmaniasis among immunosuppressed individuals.

Case reports:

Case 1: more than MCL, this is a case of disseminated leishmaniasis (DisL) in an immunosuppressed individual. Here the predominant mucosal involvement appears to be nasal (no details are provided regarding the degree of nasal involvement), and the oral involvement is confined to the upper lip involvement. This is unusual even in immunosuppressed individuals, considering that lips, gums, tongue, and hard palate are extremely infrequent in new-world MCL³.
Case 2: again, this is a case of DisL in an immunocompetent individual. Here the mucosal involvement is more typical, but an HIV seronegative status is not enough to classify the patient as immunocompetent. A better characterisation of this individual is required.
Case 3: again, another case of DisL in an immunocompromised patient. It's recommended to improve the quality of picture 1d. As mentioned before gums are unusual in new-world MCL. MCL is not commonly associated with lymphadenopathy. Both findings, and in the absence of parasitologic or histologic characterisation of the oral lesion makes it essential to consider other infectious diseases, importantly in an HIV-seropositive individual.
Case 4: this case is MCL, but the pathophysiology is different from the prior cases. Here, more than a lymphatic/hematologic dissemination, what generated the MCL was a direct inoculation on the lip or a skin inoculation close to a mucosal structure. This case is clearly, utterly different from the rest and hard to classify as an unusual manifestation or among immunosuppressed individuals.
Case 5: again, another DisL in an apparently immunocompetent patient. No details were provided here regarding the HIV serologic status or other potential sources of immunosuppression.
Case 6: again, another DisL in an immunosuppressed individual. In this case, there is not any oral or mucosal involvement (only cutaneous lesions are described). Then, this case must be removed from the report.
Case 7: there is a lack of evidence to catalogue this case as MCL. Besides the facial cutaneous lesions (only localised cutaneous leishmaniasis?), lesions described in the oral mucosa are unusually located, and an alternative explanation must be considered (metastatic melanoma?). It's not clear where the sample for PCR was obtained. With this unclear clinical and parasitological description, it's inaccurate to define the case as MCL.

Discussion:

Paragraph 3, lines 1-2: MCL is potentially fatal, mainly when larynx or trachea are affected. From that scenario, it's incorrect to describe them as a facial involvement.
Paragraph 4, lines 1-2: as suggested in the first observation of the introduction section, authors are suggesting MCL is generally associated with VL or immunosuppression. That is probably acceptable in the context of Sudanese MCL; however, this is not the epidemiological context of the study. Regarding immunosuppression, as discussed in the same observation, due to the lack of coexistence between Leishmaniasis and immunosuppressive conditions, there is not any evidence supporting this affirmation. The references used to support this statement are case reports which were not designed to measure the prevalence of MCL among immunosuppressed individuals.
Paragraph 5, lines 6-7: the high rate of recurrences observed in these cases are not necessarily related to therapeutic issues. Immunosuppression is probably the primary determinant of therapeutic failure.
Paragraph 6, lines 6-8: again, this affirmation is contradictory with the findings of this report. Only one case was purely a "primary" MCL, in the rest, the predominant manifestation was the development of disseminated cutaneous lesions.
Paragraph 8, lines 5-6: the reason why systemic therapy was administered in all these cases is that systemic treatment is the only standard therapeutic regimen for MCL (not due to resistance issues). For a better understanding of current therapeutic recommendations, authors must review citation four⁴ and update reference 9.
Paragraph 9: no local therapy is currently recommended for MCL. This information must be improved or removed.

Conclusions:

Paragraph 2: what other infections must be considered as a differential diagnosis among oral lesions?

Is the background of the cases’ history and progression described in sufficient detail?

Partly
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Partly
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Partly
Is the conclusion balanced and justified on the basis of the findings?

Partly

References

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Infectious and Tropical Diseases, Neglected Tropical Diseases, New-World Leishmaniases.

Respond to this report

Responses (0)

Alongside their report, reviewers assign a status to the article:

Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested

Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.

Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions

[1] 1. Mignogna MD, Celentano A, Leuci S, et al.: Mucosal leishmaniasis with primary oral involvement: a case series and a review of the literature. Oral Dis. 2015; 21(1): e70–8. PubMed Abstract | Publisher Full Text

[2] 2. World Health Organization: Control of the leishmaniases. World Health Organ Tech Rep Ser. 2010; (949): xii–xiii, 1–186, back cover. PubMed Abstract

[3] 3. Pellicioli AC, Martins MA, Sant'ana Filho M, et al.: Leishmaniasis with oral mucosa involvement. Gerodontology. 2012; 29(2): e1168–71. PubMed Abstract | Publisher Full Text

[4] 4. Crovetto-Martínez R, Aguirre-Urizar JM, Orte-Aldea C, et al.: Mucocutaneous leishmaniasis must be included in the differential diagnosis of midline destructive disease: two case reports. Oral Surg Oral Med Oral Pathol Oral Radiol. Elsevier Inc.; 2015; 119(1): e20–6. PubMed Abstract | Publisher Full Text

[5] 5. Celentano A, Ruoppo E, Mansueto G, et al.: Primary oral leishmaniasis mimicking oral cancer: a case report. Br J Oral Maxillofac Surg. British Association of Oral and Maxillofacial Surgeons; 2015; 53(4): 396–8. PubMed Abstract | Publisher Full Text

[6] 6. Cruz AF, Resende RG, Albuquerque DR, et al.: Mucosal leishmaniasis in Brazilian patients: two case reports with similar clinical presentation and different approaches. Oral Surg Oral Med Oral Pathol Oral Radiol. Elsevier Ltd; 2016; 122(6): e199–203. PubMed Abstract | Publisher Full Text

[7] 7. Okumura Y, Yamauchi A, Nagano I, et al.: A case of mucocutaneous leishmaniasis diagnosed by serology. J Dermatol. 2014; 41(8): 739–42. PubMed Abstract | Publisher Full Text

[8] 8. Cobo F, Rodríguez-Granger J, Gómez-Camarasa C, et al.: Localized mucosal leishmaniasis caused by Leishmania infantum mimicking cancer in the rhinolaryngeal region. Int J Infect Dis. 2016; 50: 54–6. PubMed Abstract | Publisher Full Text

[9] 9. Blum J, Lockwood DNJ, Visser L, et al.: Local or systemic treatment for New World cutaneous leishmaniasis? Re-evaluating the evidence for the risk of mucosal leishmaniasis. Int Health. Royal Society of Tropical Medicine and Hygiene; 2012; 4(3): 153–63. PubMed Abstract | Publisher Full Text

[10] 10. Gomes CM, Paula NA, Morais OO, et al.: Complementary exams in the diagnosis of American tegumentary leishmaniasis. An Bras Dermatol. 2014; 89(5): 701–9. PubMed Abstract | Publisher Full Text | Free Full Text

[11] 11. Almeida TF, da Silveira EM, Dos Santos CR, et al.: Exclusive Primary Lesion of Oral Leishmaniasis with Immunohistochemical Diagnosis. Head Neck Pathol. 2016; 10(4): 533–7. PubMed Abstract | Publisher Full Text | Free Full Text

[12] 12. Passi D, Sharma S, Dutta S, et al.: Localised leishmaniasis of oral mucosa: report of an unusual clinicopathological entity. Case Rep Dent. Hindawi Publishing Corporation; 2014; 2014: 753149. PubMed Abstract | Publisher Full Text | Free Full Text

[13] 13. Cobo F, Aliaga L, Talavera P, et al.: The histological spectrum of non-granulomatous localized mucosal leishmaniasis caused by Leishmania infantum. Ann Trop Med Parasitol. 2007; 101(8): 689–94. PubMed Abstract | Publisher Full Text

[14] 14. Ramos A, Múñez E, García-Domínguez J, et al.: Mucosal leishmaniasis mimicking squamous cell carcinoma in a liver transplant recipient. Transpl Infect Dis. 2015; 17(3): 488–92. PubMed Abstract | Publisher Full Text

[15] 15. Rathnayake D, Ranawake RR, Sirimanna G, et al.: Co-infection of mucosal leishmaniasis and extra pulmonary tuberculosis in a patient with inherent immune deficiency. Int J Dermatol. 2010; 49(5): 549–51. PubMed Abstract | Publisher Full Text

[16] 16. Torrico F, Parrado R, Castro R, et al.: Co-Infection of Leishmania (Viannia) braziliensis and HIV: report of a case of mucosal leishmaniasis in Cochabamba, Bolivia. Am J Trop Med Hyg. 2009; 81(4): 555–8. PubMed Abstract | Publisher Full Text

[17] 17. Lee GL, Woods KL, Clark L, et al.: Short communication: mucocutaneous leishmaniasis in HIV-related immune reconstitution syndrome. AIDS Res Hum Retroviruses. 2015; 31(9): 889–92. PubMed Abstract | Publisher Full Text

[18] 18. Gois L, Badaró R, Schooley R, et al.: Immune response to Leishmania antigens in an AIDS patient with mucocutaneous leishmaniasis as a manifestation of immune reconstitution inflammatory syndrome (IRIS): a case report. BMC Infect Dis. 2015; 15(1): 38. PubMed Abstract | Publisher Full Text | Free Full Text

[19] 19. Madeddu G, Fiori ML, Ena P, et al.: Mucocutaneous leishmaniasis as presentation of HIV infection in Sardinia, insular Italy. Parasitol Int. Elsevier Ireland Ltd; 2014; 63(1): 35–6. PubMed Abstract | Publisher Full Text

[20] 20. Nadler C, Enk CD, Leon GT, et al.: Diagnosis and management of oral leishmaniasis--case series and literature review. J Oral Maxillofac Surg. American Association of Oral and Maxillofacial Surgeons; 2014; 72(5): 927–34. PubMed Abstract | Publisher Full Text

[21] 21. Baglieri F, Scuderi G: A case of mucosal leishmaniasis of the tongue in a kidney transplant recipient. Int J Dermatol. 2012; 51(5): 597–600. PubMed Abstract | Publisher Full Text

[22] 22. González U, Pinart M, Rengifo-Pardo M, et al.: Interventions for American cutaneous and mucocutaneous leishmaniasis. Cochrane Database Syst Rev. 2009; (2): CD004834. PubMed Abstract | Publisher Full Text

[23] 23. Palmeiro MR, Rosalino CM, Quintella LP, et al.: Gingival leishmaniasis in an HIV-negative patient. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007; 104(6): e12–6. PubMed Abstract | Publisher Full Text

[24] 24. de Oliveira Duque MC, Quintão Silva JJ, Soares PAO, et al.: Comparison between systemic and intralesional meglumine antimoniate therapy in a primary health care unit. Acta Trop. 2019; 193: 176–182. PubMed Abstract | Publisher Full Text

[25] 25. Fernandes HJ, da Silva RE, Ramalho DB, et al.: Safety profile of meglumine antimoniate intralesional infiltration for cutaneous leishmaniasis. Expert Rev Anti Infect Ther. 2020; 18(4): 381–387. PubMed Abstract | Publisher Full Text

[26] 26. Arboleda M, Barrantes S, Úsuga LY, et al.: Successful treatment of cutaneous leishmaniasis with intralesional meglumine antimoniate: A case series. Rev Soc Bras Med Trop. 2019; 52: e20180211. PubMed Abstract | Publisher Full Text

Orofacial manifestations of mucocutaneous leishmaniasis: a case series from Brazil

Abstract

Keywords

Revised Amendments from Version 1

Introduction

Case reports

Case 1

Figure 1.

Case 2

Case 3

Case 4

Figure 2.

Case 5

Figure 3.

Case 6

Case 7

Figure 4.

Discussion

Conclusions

Data availability

Underlying data

References

Comments on this article Comments (0)

Open Peer Review

Comments on this article Comments (0)

Open Peer Review

Reviewer Status

Reviewer Reports

Comments on this article

Browse by related subjects

Competing Interests Policy

Stay Updated