Post-kala-azar dermal leishmaniasis

doi:10.1016/S1473-3099(03)00517-6

The Lancet Infectious Diseases

Volume 3, Issue 2, February 2003, Pages 87-98

https://doi.org/10.1016/S1473-3099(03)00517-6 Get rights and content

Summary

Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL); it is characterised by a macular, maculopapular, and nodular rash in a patient who has recovered from VL and who is otherwise well. The rash usually starts around the mouth from where it spreads to other parts of the body depending on severity. It is mainly seen in Sudan and India where it follows treated VL in 50% and 5–10% of cases, respectively. Thus, it is largely restricted to areas where Leishmania donovani is the causative parasite. The interval at which PKDL follows VL is 0–6 months in Sudan and 2–3 years in India. PKDL probably has an important role in interepidemic periods of VL, acting as a reservoir for parasites. There is increasing evidence that the pathogenesis is largely immunologically mediated; high concentrations of interleukin 10 in the peripheral blood of VL patients predict the development of PKDL. During VL, interferon γ is not produced by peripheral blood mononuclear cells (PBMC). After treatment of VL, PBMC start producing interferon γ, which coincides with the appearance of PKDL lesions due to interferon-γ-producing cells causing skin inflammation as a reaction to persisting parasites in the skin. Diagnosis is mainly clinical, but parasites can be seen by microscopy in smears with limited sensitivity. PCR and monoclonal antibodies may detect parasites in more than 80% of cases. Serological tests and the leishmanin skin test are of limited value. Treatment is always needed in Indian PKDL; in Sudan most cases will self cure but severe and chronic cases are treated. Sodium stibogluconate is given at 20 mg/kg for 2 months in Sudan and for 4 months in India. Liposomal amphotericine B seems effective; newer compounds such as miltefosine that can be administered orally or topically are of major potential interest. Although research has brought many new insights in pathogenesis and management of PKDL, several issues in particular in relation to control remain unsolved and deserve urgent attention.

Section snippets

Clinical features

The clinical features have been best described in reports from Sudan and India and are summarised in table 1.

Epidemiology

PKDL occurs mainly in L donovani-endemic areas and most studies reported are from Asia (mainly India) and east Africa, mainly Kenya and Sudan (table 1).

Parasites

Several studies from Sudan showed that in cultures from bone marrow or lymph node aspirates from patients with VL analysed by isoenzyme electrophoresis, L donovani, L infantum, and Leishmania archibaldi, which takes an intermediate position in the cladogram, are seen.68, 69, 70 However, the three species were all seen to be L donovani sensulato by Southern blotting and fingerprinting and were clearly different from a L infantum reference strain,⁶⁹ which supports association between VL and PKDL

Pathogenesis and immunology

The exact mechanisms underlying the development of PKDL still remain to be elucidated. There is accumulating evidence, however, that (developing) immune responses have a major role.

In VL a specific cell-mediated immune (CMI) response to the leishmania parasite is absent, and only develops after treatment. This can be measured in vitro in experiments in which peripheral blood mononuclear cells (PBMC) are stimulated or in vivo by the leishmanin skin test.

Early studies from India showed CMI

Pathology

Irrespective of the clinical forms the epidermis shows several changes in different combinations. These include hyperkeratosis, parakeratosis, focal acanthosis, or atrophy of the rete pegs, and liquifaction degeneration of the basal cells.⁸⁸ The last is associated with focal infiltration of the basal layer by lymphocytes. Under electron microscopy the lymphocytes are in intimate contact with melanocytes and basal keratinocytes. The latter cells seem to be damaged by the infiltrating

Predictors of PKDL

No convincing clinical predictors have been identified that are helpful to predict who will develop PKDL and who will not. One Sudanese study showed spleen size at time of VL to be correlated with development of PKDL,⁸⁵ but another study did not confirm this.² In a further study from Sudan it was suggested that inadequate treatment regimens may be important.² This possibility was also suggested from India where all patients presenting with PKDL had short duration of treatment for VL.³ It is

Diagnosis

In most endemic areas diagnosis will be made clinically by a history of previous VL, the temporal association with VL, the distribution and appearance of the lesions, by ruling out other disorders, and by the response to treatment. Parasitological confirmation may be sought if in doubt. Studies from India showed that smears are more likely to show amastigotes if taken from a larger lesion or from nodular (67–100%) lesions compared with papulard (36–69%) and macular lesions (7–33%).4, 96

Treatment

There are few controlled studies on the management of PKDL and most data come from small case series. In addition, there are differences in approach according to geographical area. An overview of studies available is given in table 2.

Conclusion

PKDL is now recognised as a frequent complication of VL in most endemic areas with important clinical and epidemiological implications. Although in the past decade studies have considerably increased our understanding of PKDL, many issues remain unresolved and should be the subject of further research (panel). These might include studies that increase our basic understanding in pathogenesis and management, but should also be focused on the public-health aspects of PKDL, especially in relation

Search strategy and selection criteria

The data in this review were from papers identified from PubMed searches using the terms, “post-kala-azar dermal leishmaniasis”, “post-kala-azar”, “dermal leishmaniasis”, “PKDL”, and “PKADL”. Additional data originated from papers in reference lists of reviewed articles and from the authors' personal archives. Reference were selected for their scientific contribution to various aspects of PKDL. Case reports were used for areas in which not other studies were available. English and French papers

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