Prevalence of Co-existing dermatological manifestations in Cutaneous Leishmaniasis

Introduction Leishmaniasis is a vector borne protozoan infestation and manifested as cutaneous, visceral and muco-cutaneous lesions in human. Visceral form is the most virulent type and the annual incidence was 0.2-0.4 million cases around the world.But, in Sri Lanka, Cutaneous Leishmaniasis (CL) is a newly established disease and is emerging as a threat to public health.In Sri Lanka the condition is still not fully investigated nor well studied. Method The aim of this descriptive cross-sectional study was to determine the prevalence of CL in the patients coming to the dermatology unit and clinic of the District General Hospital, Matara, Sri Lanka. The study was conducted from August 2016 to March 2017. Results There were 129 participants subjected to Leishmanin Skin Test accompanied with direct interviews and physical examination. The most of participants were males (52.8%), 68.4% of them unskilled. The highest prevalent type was Non scaly nodule (45.0%). Most common site of lesion was arm (47.1%). Majority had a single lesion (76.7%). Co-existing skin manifestations of hypopigmentation (36.9%) was the commonest. In (63.6%), co-existing skin lesions involved only less than 2% of body surface area. The hypopigmentation was significantly associated with Age, Sex and work outdoor while photodermatitis was significantlyassociated with age and photosensitivity. Eczematisation was significantly associated with diabetes mellitus and hyperlipidaemia. Conclusions Cutaneous Leishmaniasis is more prevalent among 31 -41-year age group and males. Majority are primary, single, early presentationandnon-scaly nodule. The limbs are the commonest affected site. DOI: http://doi.org/10.4038/jrcs.v24i1.66


Introduction
Leishmaniasis is a vector borne protozoan infestation and it is manifested as cutaneous, visceral and muco-cutaneous lesions in human. Visceral form is the most virulent type and the annual incidence is 0.2-0.4 million cases around the world. Majority (90%) is reported from India, Bangladesh, Nepal, Sudan, Ethiopia and Brazil. The most common manifestation is cutaneous lesions and it is prevalent in Afghanistan, Algeria, Iran, Saudi Arabia, Syria, Brazil, Colombia, Peru and Bolivia. Annual incidence is around 0.7 -1.2 million globally. In addition, it is found recently in Mexico, Central America, South America and United States of America 1 .
In Sri Lanka, CL is a newly established disease and is emerging as a threat to public health. It was considered as exotic disease and cases were limited to Middle East returnees. But in 1992 the first case of locally acquired patient was found in Ambalantota and the second case was found in 1995 in Mahiyanganaya. Until year 2000, cases were sporadic in many districts of Sri Lanka. Now the cases are increasing in number mostly in Anuradhapura, Polonnaruwa, Hambantota and Matara districts. CL is transmitted by sand-fly called phlebotomus argentipes. Initially it was thought that transmission is autochthonous but in 2009 it was found dog as a reservoir in Sri Lanka. 3 To minimize the disease burden in Sri Lanka, it is important to identify patients by the clinicians who are not only working in the dermatology clinics, also in other units like dental, medical and ear-nose-throat clinics. Diverse clinical presentations ranging from acne-form papules to complicated ulcers are challenging to clinicians. Associations of coexisting dermatological conditions, further complicate the accurate diagnosis.
Polymorphic presentations of CLhave become more prevalent in many parts of the country.Sometimes, Co-existing manifestation is the first clinical presentation of the disease.
CL usually present as papules, nodules or non-healing ulcers. But different morphological presentations and coexisting manifestations could mimic various skin disorders. This can delay the diagnosis of the disease. A study conducted in Punjab; Pakistan has revealed 5.7% of unusual presentations of the disease. 4 Majority of them presented as lupoid lesions (13 cases, 34%), sporotrichoid (12%) and paronychia (7.3%). In a case series studydone in Muzaffarabadhas revealed lesions resembling lupus vulgaris or lupus erythematosus on the face or elsewhere and was included in the study 5 . Such variations in the clinical and pathological presentations may be due to differences either in the host's immunologic reactivity or species-specific activity.Five Iranian females have shown infiltrative erythematous lesions of CLcovering the centre of the face and resembling erysipelas 6 . Similar case of erysipeloid form been reported from Tunisia 7 . Ethiopian case study they described about 2 patients with unusual presentations of diffuse CLpresenting with large hypopigmented skin lesions mimicking borderline-tuberculoid leprosy. 9 Rare presentationsof eczematisation were reported in many studies. 10,11 Rare presentation of nonhealing ulcer over a lip in an Italian man who left the country 19-year back was diagnosed as Leishmaniasis. 2 HIV-Leishmania co-infection has caused unusual presentations and different treatment responses in India. 13,14,15 Recent study done in Sri Lanka revealed variety of atypical lesions of CL and their clinical profile and treatment outcome. 8 This study was planned tohelp in identifying demographic correlates, common co-existing skin manifestations of CL and their prevalence as well as correlations between severity of primary lesions and other co-existing manifestations. 3 Another aim was to identify the correlations between clinical response to medications and behaviour of the photosensitivity reactions.

Methods
This wasa hospital-based, descriptive cross-sectional study which was carried out in Dermatology unit and clinic, at District General Hospital, Matara, Sri Lanka.
All cytological or histologically confirmed patients with CL who attended to Dermatology unit, DGH Matarafrom August 2016 to March 2017 were recruited except for patients with past history of photosensitivity, genetically predisposed patients for photosensitivity, patients with other skin disorders which could lead to id reactions, patients with atopic dermatitis or other pre-existing skin disease which could result in generalized eczema or exfoliative dermatitis, severely ill patients and children below 5 years of age were excluded from study.
The participation was entirely on a voluntary basis and informed consent was obtained from the study participants prior to data collection.
Ethical clearance was obtained from the Ethical Review Committee of the Faculty of Medicine, University of Ruhuna. The questionnaire was pre tested and validated at Teaching Hospital, Karapitiya. Interviewer administered questionnaires and data record sheets were used to collect data. The questionnaire consisted of three parts, Socio-demographic characteristics of the participants, Clinical history, Clinical presentation and observation.Each questionnaire consistedof close ended questions includingsociodemographic data, observation findings of lesions, parametric data on lesions and outcome assessment of lesions.
Outcome variables were different types of co-existing dermatological manifestations. Presence of hyper or hypopigmentation around primary lesion, other cutaneous features like photosensitive lesions and interface dermatitis with its morphological subtype, exfoliative dermatitis, surrounding eczematisation, erysipeloid and lupoid lesions were assessed clinically with their extent of involvement which was calculated according to rule of nine body surface area (BSA).Also, primary lesion was photographed with a scale in centimetres and processed in AutoCAD software to obtain the accurate measurement and size of primary skin lesion.

Socio Demographic Characteristics
The total of 129 patients were enrolled in this study. Table 1 shows the distribution of selected socio-demographic characteristics among respondents.

Table.04 Associated Co-morbidities
Majority (67.4%) didn't have any co-morbidities. 21.7.0% patients of CL in the study were diagnosed to have hypertension which was the most prevalent comorbid factor followed by diabetes mellitus (17.1%) and hyperlipidaemia (13.1%).   The hypopigmentation was significantly associated with age, sex and work at outdoor while photodermatitis was associated significantly with age, and photosensitivity at 95% confidence level.

Discussion and Conclusions
Age and gender association of CL were constant with previous findings of studies in the country. 8 Although he commonest age group was 21 -30 years in this sample CL was most prevalent among youngsters, below 20 years. In Sri Lanka 21 -30 age group people engage in moreoutdoor activities than children, household clustering and peri domestic transmission could be causing this difference. Non scaly nodule was the commonest presentation (45.0%) in this study which is nearly similar to the past findings in Sri Lanka whereas the ulcerative nodule was the commonest type of CL in Pakistan and Brazil. This may be due to difference of species. Many patients have presented before 4 weeks from the onset of skin lesion/s (44.9%) which is somewhat earlier than previous studies. Raising awareness among general public regarding the condition leading to enhance self-referrals is the probable reason for this early presentation.
76.7% of participants of our study had had only single primary lesion of CL which is slightly lesser than recent findings of other local studies. 8 Limbs (Upper limbs > Lower limbs) are the commonest sites for primary skin lesions in our study. The percentages are nearly similar to the other studies done locally and south Asian continent 8 . 58% of patients in this study had either one or multiple comorbidities in which the hypertension was the commonest followed by diabetes mellitus. Further, analysis revealed eczematisation was more prevalent among patient with diabetes mellitus.
27.4% of skin lesions were between 1.1 -2.0cm 2 followed by 20.0% of 21 -3.0 cm 2 . Altogether these two is closely similar to the findings for the size of primary skin lesions in India.
Outdoor activities were the most prevalent predisposing factor for CL in both local s well as international setting. Similarly, we found the same factor predisposed to cause co-existing other skin manifestations of CL(69.0%).
Even though many patients presented with primary skin lesion of CL, some patients presented with other nonclassical lesions such as photodermatitis, id reactions, follicular papules of eczematised reactions in which examination revealed primary lesion.
The prevalence these co-existing skin manifestations were not described in detail inpreviousstudies. Development of more treatment resistant virulent strains of Leishmania Donovan organism might be causing more severe immune response of CL, could be responsible for this recent appearance of other co-existing skin manifestations.
Analysis revealed both hypopigmentation and photodermatitis decreases when age increases. Reduced outdoor activities in old population could be causing this.
Moreover, hypopigmentation was less among patient with outdoor activities.
Besides, Photodermatitis was more prevalent on patients who had past history of photodermatitis. utaneous Leishmaniasis is more prevalent in 31 -41 years and male sex. Majority had presented very early to the dermatology.
Single and Non-scaly nodule mainly on limbs was the commonest presentation. Although majority didn't have comorbidities, eczematisation was more prevalent on patients with diabetes mellitus. Primary disease was common among people without-door based occupations.
Significant proportion of patients with CL had other co-existing skin manifestations which are mainly hypopigmentation, photodermatitis, eczematisation and follicular papules.

Recommendations
Being a very common skin disease establishment of more disease awareness programmes regarding domestic prevention and mass preventive programmes among general public are recommended in order to reduce the burden of the disease.
Rising cases of co-existing other skin manifestations in CL will need more research to find out the immunological basis / pathogenesis of these manifestations.
Teaching programmes are recommended to medical professionals to identify the primary lesion when patients presented with other co-existing skin manifestations in early stage of disease and make tertiary care referral and notification to prevent delaying of treatment.