|Year : 2017 | Volume
| Issue : 2 | Page : 87-91
Post-Kala-Azar Dermal Leishmaniasis Associated With Oral Lesions: A Rare Case Report
Akansha Misra1, Deepankar Misra2, Shalu Rai2, Mansi Khatri2
1 Department of Oral Pathology, Institute of Dental Studies and Technologies, Modinagar, U.P., India
2 Department of Oral Medicine and Radiology, Institute of Dental Studies and Technologies, Modinagar, U.P., India
|Date of Web Publication||28-Jun-2017|
Senior Lecturer, Institute of Dental Studies and Technologies, Modinagar - 201 201, U.P.
Source of Support: None, Conflict of Interest: None
Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis that usually occurs after visceral leishmaniasis (VL) caused by Leishmania donovani and characterized by macular, maculopapular, and nodular skin lesions on the whole body surface. It is a late cutaneous manifestation of VL in untreated or inadequately treated patients, first described by Brahmachari in 1922. In India, PKDL occurs in 6–20% of the cases of VL, 6 months to 5 years after the apparently successful treatment of VL. The diagnosis of PKDL presents a challenge due to low parasite burden in the lesions. We report a case of PKDL that presented with polymorphic skin lesions along with the involvement of the oral cavity including an insight into the recent advances in diagnosis, pathogenesis, and case management.
Keywords: Diagnosis, oral lesions, post-kala-azar dermal leishmaniasis
|How to cite this article:|
Misra A, Misra D, Rai S, Khatri M. Post-Kala-Azar Dermal Leishmaniasis Associated With Oral Lesions: A Rare Case Report. MAMC J Med Sci 2017;3:87-91
|How to cite this URL:|
Misra A, Misra D, Rai S, Khatri M. Post-Kala-Azar Dermal Leishmaniasis Associated With Oral Lesions: A Rare Case Report. MAMC J Med Sci [serial online] 2017 [cited 2019 Nov 11];3:87-91. Available from: http://www.mamcjms.in/text.asp?2017/3/2/87/209012
| Introduction|| |
Post-kala-azar dermal leishmaniasis (PKDL), first described in India by Brahmachari in 1922, is a dermatologic manifestation that usually occurs months to years after the resolution of visceral leishmaniasis (VL) caused by Leishmania donovani. It is restricted to certain endemic areas such as India, Bangladesh, Nepal, and Sudan, and the incidence of PKDL after VL varies from 5% to 10% in the Indian subcontinent. PKDL is reported to occur in 5–10% of the patients treated for kala-azar and occasionally in individuals with no history of kala-azar. Among the mucosal lesions, the oral mucosa is affected, presenting with granulomatous nodules at the angles of the mouth, over the dorsum of the tongue, the buccal mucosa, or the soft palate.
Cytokines, drugs, and ultraviolet light have been attributed as possible factors involved in the pathogenesis., The pathology is well documented and is characterized by hyperkeratosis, parakeratosis, acanthosis, follicular plugging, and liquefaction degeneration of the basal layer of the epidermis. The dermis presents with varying intensities of inflammation with scanty parasites associated with an infiltrate composed of lymphocytes, macrophages, and epithelioid cells.
| Case Report|| |
A 40-year-old female patient reported to the Department of Oral Medicine and Radiology with the chief complaint of pain and bleeding from the left cheek region of the mouth since 1 year.
Two years before reporting to us, the patient had developed fever, and on consulting a local physician, she was treated with corticosteroids.
On general examination/dermatological examination, the patient presented with multiple purplish red papular lesions varying in size from 0.5 to 1 cm in greatest diameter over the flexor and the extensor surface of the forearm, the arm bilaterally, and the neck [Figure 1]. The papular lesions were interspersed with areas of vasculitis. On palpation, the lesions were nontender and nonulcerative. White scaly lesions were visible over the trunk [Figure 2].
|Figure 1: Purplish red papular lesions on the flexor and the extensor surface of the forearm|
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Extraoral examination revealed an erythematous rash extending over the nasal bridge and malar prominence bilaterally suggestive of butterfly/malar rash [Figure 3]. Diffuse erythematous papules were also present over the forehead, superior palpebral sulcus bilaterally (upper eyelid), and lower third of the face.
|Figure 3: Malar rash extending over the nasal bridge and the nasal prominence|
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Intraoral examination revealed a solitary growth on the left retrocommissural region measuring about 1.5 cm in greatest dimensions. The overlying mucosa was erythematous and ulcerated in the center. On palpation, the growth was sessile, tender, and bled on provocation [Figure 4]. Fine, white radiating striae interspersed with the areas of melanin pigmentation were seen on the right buccal vestibule and the buccal mucosa extending from 44 to 48 region [Figure 5]. Similar lesions were also present on the palate. The tongue was atrophic and fissured. An incisional biopsy of the growth was performed and was sent for histopathological examination. Histopathology revealed connective tissue stroma, which was delicately fibrillar with dense, chronic inflammatory cell infiltrate suggestive of chronic granulomatous infection [Figure 6].
|Figure 6: Photomicrograph showing the connective tissue stroma fibrillar with dense chronic inflammatory cell infiltrate (hematoxylin and eosin, ×400)|
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On the basis of history, examination, and histopathologic findings, systemic lupus erythmatosus (SLE) was diagnosed, and rheumatoid arthritis, dermatomyositis, vasculitis, and rhupus (overlap of SLE and rheumatoid arthritis) were differentially diagnosed. For the confirmation of SLE, the patient was subjected to the following investigations: complete blood picture, urine analysis for protein estimation, immunologic investigations such as Rh factor, antinuclear antibodies (ANA), and Anti double stranded DNA (anti-dsDNA). The blood picture revealed features of anemia along with reticulocytosis. Hemolytic anemia was confirmed after biochemical examination, which revealed increased unconjugated bilirubin, increased lactate dehydrogenase, and decreased haptoglobin levels. Proteinuria (600 mg/24 h) was found on urine analysis, and the patient was Rh positive. The above findings were indicative of SLE. However, other serologic investigations, that is, ANA and anti-dsDNA, were negative. Hence, the diagnosis of SLE was ruled out.
On further questioning, the patient, reported a previous history of hospitalization 3 years back due to high-grade fever and skin lesions (on the face to start with and then spread to the entire body) after her return from Bangladesh. She was diagnosed of kala-azar and was treated using high-dosage corticosteroids. The skin lesions subsided for a year and reappeared with more intensity. Considering this pertinent history and after taking an opinion from a dermatologist, a provisional diagnosis of PKDL was made, and the differential diagnoses of leprosy, sarcoidosis, and actinic dermatitis were considered. The patient was subjected to the following investigations: fresh skin biopsy of the lesion (papule) for parasite isolation and rK39 rapid diagnostic Enzyme linked Immunosorbent Assay (ELISA). On histopathology, the epithelium appeared stretched with flat epithelial connective tissue interface, with grenz zone just beneath the epithelium and dense lymphocytic infiltration along with multiple Leishman–Donovan bodies [Figure 7] and [Figure 8]. rK39 Test was performed using nitrocellulose dipstick and was found to be positive. The patient was referred to a higher center for other confirmatory investigations such as polymerase chain reaction (PCR) and detection of parasitic Deoxyribonucleic Acid (DNA) in the tissue samples, but was lost to follow-up.
|Figure 7: Photomicrograph showing the stretched epithelium with flat epithelial connective tissue interface, dense lymphocytic infiltration along with Leishman–Donovan bodies (black arrow) (hematoxylin and eosin, ×100)|
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|Figure 8: Photomicrograph showing Leishman–Donovan bodies (hematoxylin and eosin, ×400)|
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| Discussion|| |
Leishmaniasis is a group of diseases caused by various species of the protozoan parasites of the genus Leishmania. PKDL is a dermal complication caused as a sequel to VL. The prevalence of PKDL in India among the general population has been estimated to be around 5–15% of the VL cases after months or several years of remission from infection. The interval between VL and PKDL is short, with all cases occurring 0–13 months after treatment, usually within the first 6 months.,
In our case, despite initial suspicions of SLE due to the presence of characteristic malar/butterfly rash, the diagnosis of PKDL was confirmed through histopathological and serological tests (rK39 Test).
Various rare morphological forms of PKDL, including mucosal, xanthomatous, verrucous, papillomatous, hypertrophic, fibroid, atrophic, and extensive hypopigmentation, have been documented. Jha et al. in 2012 reported a case PKDL in Bihar, India, presenting as an ulcerated chronic paronychia such as the lesion on the digit of the patient. The diagnosis of PKDL in their patient was confirmed due to the presence of juicy lesions around the mouth with pre-existing hypopigmented lesions. They described three common morphological forms of PKDL found in India, of which one or two may predominate in a patient and occur as erythema and induration on the butterfly area of the face; multiple symmetrical hypopigmented macules that may coalesce each other; and the combinations of papules, nodules, and plaques. The lesions may affect the oral mucosa and present as granulomatous nodules at the commissural area, the dorsum of the tongue, the buccal mucosa, or the soft palate. The oral or perioral mucosal involvements resemble the dermal/mucosal manifestations of conditions such as drug reactions, secondary syphilitic lesions, oral lichen planus, lupus erythematosus, or pemphigus vulgaris. However, for each of these conditions, the typical descriptions of the skin and/or the mucosal lesions are demonstrable, along with a suggestive history. Our case reported with a similar solitary nodular growth on the left retrocommissural region.
The distribution of PKDL may present as three clinical grades of severity. Grade 1 is associated with a scattered maculopapular or nodular rash on the face with or without some lesions on the upper chest and the arms. Grade 2 presents as a dense maculopapular or nodular rash covering most of the face and extending to the chest, the back, the upper arms, and the legs, gradually becoming less distally, with only the scattered lesions on the forearms and the legs. Grade 3 is defined as a maculopapular or nodular rash covering most parts of the body, including the hands and the feet. In grade 3, crusting, ulceration, sloughing, scaling, and spreading to the mucosa of the lip (cheilitis) and the palate may occur. The case had grade 2 type, because the lesions were present on the flexor and the extensor surface of the forearm, the arm bilaterally, and the neck and the face.
The diagnosis of PKDL presents a challenge due to low parasite burden in the lesions. Presently, the diagnosis is based on clinical and epidemiological parameters. The demonstration of parasite in the slit smear or by culture of the dermal tissue is considered to be an effective method; however, it is not routinely used, because the reported sensitivity is believed to be as low as 58%. Commonly used methods for diagnosis include the demonstration of parasite in tissues of relevance by light microscopic examination of the stained specimen, in-vitro culture, or animal inoculation; immunodiagnosis by the detection of parasite antigen in the tissue, the blood, or the urine samples, by the detection of nonspecific or specific antileishmanial antibodies, or by assay for Leishmania-specific cell-mediated immunity; or by the detection of the parasite DNA in the tissue samples. The potential of serological tests such as direct agglutination test and ELISA for the diagnosis of PKDL has been evaluated, and these show promise as rapid and noninvasive tests. In recent times, several Leishmania genes have been cloned and characterized as a result of extensive scientific activity aimed at improving the serological methods for the diagnosis of leishmaniasis. The examples include rK39 test, A2, ORF F, rH2A, rH2B, rGBP, rLACK, rgp63, rP20, rPSA, and purified LPG.
rK39 antigen-based dipstick test is a noninvasive, nitrocellulose dip-stick immunoassay that uses a recombinant Leishmania antigen, rK39, for the detection of IgG antibodies. Various studies have been conducted to evaluate the sensitivity and the specificity of rK39 in PKDL. In India, the rK39 Test strip test has been found to be highly sensitive and reliable for the diagnosis of PKDL. The sensitivity of the strip test for VL diagnosis in India, has been reported to be 100 percent, and could correctly diagnose 95% of the cases of PKDL with polymorphic presentation, whereas with macular PKDL, the sensitivity was 73%. The specificity of the test is reported to be 100% in laboratory studies. The present patient was advised rK39 test, which was found out to be positive. rK39 test may also show positive results for malaria, enteric fever, and disseminated Tuberculosis (TB); therefore, the patient was referred to a higher center for other confirmatory investigations such as PCR but was unfortunately lost to follow-up.
The Advisory Panel of World Health Organization and National Vector Borne Disease Control Programme in India recommends the use of Amphotericin B or miltefosine 50 mg for PKDL patients in India. Miltefosine is the preferred first-line drug relatively safe for the treatment of PKDL. The second-line drug is Amphotericin B. A randomized clinical trial confirmed the efficacy and superiority of miltefosine for the treatment of cutaneous leishmaniasis compared with antimonials. Recently the management with immunotherapy has been studied and has been associated with a high cure rate of 87%., Immunotherapy was based on the use of first-generation vaccine (alum-precipitated autoclaved Leishmania major and Bacillus Calmette-Guérin (BCG)). Future studies are needed to investigate the efficacy of immunotherapy with second-generation vaccines and other drugs.
In conclusion, PKDL is a disease in which the exact mechanism and etiopathogenesis are not definitely known. The disease has only cosmetic significance as far as the patient is concerned. However, there is a great epidemiologic significance, because PKDL cases are considered to be a reservoir of VL.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Brahmachari UN. A new form of cutaneous leishmaniasis–Dermal leishmanoid. Indian Med Gaz 1927;57:125-7.
Rahman KM, Islam S, Rahman MW, Kenah E, Chowdhury MG, Zahid MM et al.
Increasing incidence of post-kala-azar dermal leishmaniasis in a population based study in Bangladesh. Clin Infect Dis 2010;50:73-6.
Salotra P, Singh R. Challenges in the diagnosis of post kala-azar dermal leishmaniasis. Indian J Med Res 2006;123:295-310.
Rathi S. Post-kala-azar dermal leishmaniasis with an atypical presentation. J Dermatol 2001;28:341-2.
Croft SL. PKDL–A drug related phenomenon? Indian J Med Res 2008;128:10-1.
] [Full text]
Singh S, Kumari V, Singh N. Predicting kala-azar disease manifestations in asymptomatic patients with latent Leishmania donovani infection by detection of antibody against recombinant K39 antigen. Clin Diag Lab Immunol 2002;9:568-72.
Jha AK, Anand V, Mallik SK, Kumar P. Post kala azar dermal leishmaniasis (PKDL) presenting with ulcerated chronic paronychia like lesion. Kathmandu Univ Med J 2012;10:87-90.
Sundar S, Reed SG, Singh VP, Kumar PC, Murray HW. Rapid accurate field diagnosis of Indian visceral leishmaniasis. Lancet 1998;351:563-5.
Salam A, Siddiqui A, Nabi SG, Bhaskar KR, Mondal D. Post kala azar dermal leishmaniasis with mucosal involvement: An unusual case presentation including successful treatment with miltefosine. J Health Popul Nutr 2013;31:294-7.
Thakur CP, Dedet JP, Narain S, Pratlong F. Leishmaniasis species, drug unresponsiveness and visceral leishmaniasis in Bihar, India. Trans R Soc Trop Med Hyg 2001;95:187-9.
Chrusciak-Talhari A, Dietze R, Chrusciak Talhari C, da Silva RM, Gadelha Yamashita EP, de Oliveira Penna G et al.
Randomized controlled clinical trial to access efficacy and safety of miltefosine in the treatment of cutaneous leishmaniasis caused by Leishmania (Viannia) guyanensis in Manaus, Brazil. Am J Trop Med Hyg 2011;84:255-60.
Musa AM, Khalil EA, Mahgoub FA, Elgawi SH, Modabber F, Elkadaru AE et al.
Immunotherapy of persistent post kala-azar dermal leishmaniasis: A novel approach to treatment. Trans R Soc Trop Med Hyg 2008;102:58-63.
Zijlstra EE, Nur Y, Desjeux P, Khalil EA, El-Hassan AM, Groen J. Diagnosing visceral leishmaniasis with the recombinant k39 strip test: Experience from the Sudan. Trop Med Int Health 2001;6:108-13.
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