|LETTER TO THE EDITOR
|Year : 2014 | Volume
| Issue : 6 | Page : 122-124
Post-kala-Azar dermal leishmaniasis: A diagnostic dilemma in a nonendemic area
Prachi Bhandare, Pankaj Shukla, Mayur Bhobe, Varadraj V Pai
Department of Dermatology, Goa Medical College, Bambolim, Goa, India
|Date of Web Publication||5-Dec-2014|
Dr. Mayur Bhobe
SPARC, Behind Chowgule College, Cupangale, Fatorda, Salcete - 403 602, Goa
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Bhandare P, Shukla P, Bhobe M, Pai VV. Post-kala-Azar dermal leishmaniasis: A diagnostic dilemma in a nonendemic area. Indian Dermatol Online J 2014;5, Suppl S2:122-4
|How to cite this URL:|
Bhandare P, Shukla P, Bhobe M, Pai VV. Post-kala-Azar dermal leishmaniasis: A diagnostic dilemma in a nonendemic area. Indian Dermatol Online J [serial online] 2014 [cited 2019 Sep 18];5, Suppl S2:122-4. Available from: http://www.idoj.in/text.asp?2014/5/6/122/146190
A 34-year-old male painter residing at Goa since 10 years, hailing from Bihar, India presented with multiple asymptomatic light coloured patches over the face and trunk since three years. The lesions started three years ago as asymptomatic, light coloured, pea sized patches that gradually increased in size and became diffusely infiltrated. There was no history suggestive of sensory or motor impairment. There was no prior history of fever, cough, epistaxis, diarrhea or history of hospitalization.
Cutaneous examination revealed nodules and hypopigmented plaques over face [Figure 1]a and b and trunk. Two nodules, one on the nose measuring 6 cm × 7 cm and other on the medial aspect of left eyebrow measuring 2 cm × 3 cm were noted. These were well defined and erythematous with a smooth, shiny and partly lobulated surface and were firm in consistency. Plaques on the face were multiple, well defined, shiny, with a few showing an erythematous hue. The plaque on the chin showed infiltration with multiple erythematous papules. The trunk showed multiple, hypopigmented, round to oval, shiny, ill-defined plaques. There was no nerve enlargement and no sensory or motor deficit. There was no significant lymphadenopathy. Systemic examination was normal and there was no organomegaly. The patient was investigated with a differential diagnosis of borderline tuberculoid leprosy, leishmaniasis, and sarcoidosis. Hematological and biochemical investigations were within the normal limits. Chest radiograph was normal and tuberculin test was negative. Abdominal ultrasound was normal. Although the slit skin smear stained with Giemsa did not reveal any Leishman-Donovan (LD) bodies, skin biopsy findings were diagnostic. It showed diffuse dense infiltrate of lymphocytes, plasma cells and macrophages involving the upper and mid dermis [Figure 2] and [Figure 3]. The macrophages predominated in a few foci with a semblance of granuloma formation. Many macrophages contained within cytoplasm tiny slightly basophilic dots suggestive of LD bodies. Nerves and appendages were spared. The overlying epidermis was atrophic. On clinicopathological correlation, a diagnosis of post-kala-azar dermal leishmaniasis (PKDL) was made. Miltefosine was planned to be started but he was unfortunately lost to follow-up.
|Figure 1: (a) Clinical photograph showing erythematous lobulated nodules, over the face obscuring the nose, (b) Closer view of hypopigmented plaque on chin showing infiltration with multiple erythematous papules|
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|Figure 2: Photomicrograph showing diffuse dense infiltrate of lymphocytes, plasma cells and macrophages involving the upper and mid dermis (H and E, x10)|
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|Figure 3: Photomicrograph showing the characteristic Leishman-Donovan bodies (H and E, x40)|
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Post-kala-azar dermal leishmaniasis caused by Leishmania donovani and rarely by Leishmania infantum occurs in 5-10% of Indian patients and is considered to be a dermal sequelae of visceral leishmaniasis (VL).  Although PKDL usually occurs following VL, it has also been reported in 15-20% of patients with no history of VL, suggesting a subclinical infection. Several host and treatment factors have been proposed to predict the progression to PKDL.  In Southeast Asia (India) transmission of VL is largely anthroponotic and since the lesions, especially papulonodules are parasite rich, patients with PKDL are a proposed reservoir of VL.  Demonstration of parasites in the dermal lesions is considered the gold standard for a diagnosis of PKDL. 
Post-kala-azar dermal leishmaniasis has been recently proposed to be a drug related phenomenon.  Administration of optimal doses of sodium stibogluconate (SSG) leading to an apparent successful cure of VL has also been linked to PKDL. Although it does not hold true in all patients, it is believed to develop in those who fail to mount an adequate immune response after infection or during their treatment for VL.  Furthermore, anti leishmanial drugs, when used at a lower dosage eliminate parasites from the viscera but not from the skin, which requires a higher dose. Hence, PKDL may also be a dose related phenomenon.  In addition, SSG unlike amphotericin B is known to increase transforming growth factor (TGF) beta and interleukin-10 (IL-10), factors that support parasite persistence. , Following the rise of resistance to pentavalent antimonials, which were largely used as the mainstay of treatment in endemic regions of our country, alternative drugs like amphotericin B deoxycholate,  liposomal amphotericin B,  miltefosine,  and paramomycin  are on rise and these are rarely reported to develop PKDL when used for treatment of VL.
Visceral leishmaniasis is characterized by Th2 immune response state with overproduction of IL-10, TGF beta and polyclonal B cell stimulation. PKDL shows a mixed T cell response and with elevated levels of IL-10 and tumor necrosis factor (TNF) alpha. , The infiltrating regulatory T cells (Tregs) are a likely source of IL-10, which ensures parasite survival.  Healing is heralded by change to Th1 immune response with increase interferon gamma and TNF beta generation. Interferon gamma augments the killing potential of macrophages. 
A high index of suspicion will be helpful in diagnosing this condition among migrants in a nonendemic area such as Goa where this is the first case to be reported.
| References|| |
Das VN, Ranjan A, Pandey K, Singh D, Verma N, Das S, et al.
Clinical epidemiologic profile of a cohort of post-kala-azar dermal leishmaniasis patients in Bihar, India. Am J Trop Med Hyg 2012;86:959-61.
Croft SL. PKDL - A drug related phenomenon? Indian J Med Res 2008;128:10-1.
Mukhopadhyay D, Dalton JE, Kaye PM, Chatterjee M. Post kala-azar dermal leishmaniasis: An unresolved mystery. Trends Parasitol 2014;30:65-74.
Koley S, Mandal RK, Choudhary S, Bandyopadhyay A. Post-kala-azar dermal leishmaniasis developing in miltefosine-treated visceral leishmaniasis. Indian J Dermatol 2013;58:241.
Mondal D, Khan MG. Recent advances in post-kala-azar dermal leishmaniasis. Curr Opin Infect Dis 2011;24:418-22.
Saha S, Mondal S, Ravindran R, Bhowmick S, Modak D, Mallick S, et al.
IL-10- and TGF-beta-mediated susceptibility in kala-azar and post-kala-azar dermal leishmaniasis: The significance of amphotericin B in the control of Leishmania donovani
infection in India. J Immunol 2007;179:5592-603.
Thakur CP, Kumar A, Mitra G, Thakur S, Sinha PK, Das P, et al.
Impact of amphotericin-B in the treatment of kala-azar on the incidence of PKDL in Bihar, India. Indian J Med Res 2008;128:38-44.
Burza S, Sinha PK, Mahajan R, Sanz MG, Lima MA, Mitra G, et al
. Post Kala-Azar dermal leishmaniasis following treatment with 20 mg/kg liposomal amphotericin B (ambisome) for primary visceral leishmaniasis in Bihar, India. PLoS Negl Trop Dis 2014;8:e2611.
Sundar S, Jha TK, Thakur CP, Sinha PK, Bhattacharya SK. Injectable paromomycin for visceral leishmaniasis in India. N Engl J Med 2007;356:2571-81.
Ganguly S, Das NK, Panja M, Pal S, Modak D, Rahaman M, et al.
Increased levels of interleukin-10 and IgG3 are hallmarks of Indian post-kala-azar dermal leishmaniasis. J Infect Dis 2008;197:1762-71.
Ganguly S, Das NK, Barbhuiya JN, Chatterjee M. Post-kala-azar dermal leishmaniasis - An overview. Int J Dermatol 2010;49:921-31.
Khalil EA, Khidir SA, Musa AM, Musa BY, Elfaki ME, Elkadaru AM, et al.
Post-kala-azar dermal leishmaniasis: A paradigm of paradoxical immune reconstitution syndrome in Non-HIV/AIDS patients. J Trop Med 2013;2013:275253.
[Figure 1], [Figure 2], [Figure 3]