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
ReviewPost-kala-azar dermal leishmaniasis
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
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